Abstract

We describe novel imaging protocols that allow detection of small cancer cell colonies deep inside tissue phantoms with high sensitivity and specificity. We compare fluorescence excited in Styryl-9M molecules by femtosecond pulses at near IR wavelengths, where Styryl-9M shows the largest dependence of the two-photon absorption (2PA) cross section on the local environment. We show that by calculating the normalized ratio of the two-photon excited fluorescence (2PEF) intensity at 1200 nm and 1100 nm excitation wavelengths we can achieve high sensitivity and specificity for determining the location of cancer cells surrounded by normal cells. The 2PEF results showed a positive correlation with the levels of MDR1 proteins expressed by the cells, and, for high MDR1 expressors, as few as ten cancer cells could be detected. Similar high sensitivity is also demonstrated for tumor colonies induced in mouse external ears. This technique could be useful in early cancer detection, and, perhaps, also in monitoring dormant cancer deposits.

©2012 Optical Society of America

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  1. M. Solomon, Y. Liu, M. Y. Berezin, and S. Achilefu, “Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring,” Med. Princ. Pract. 20(5), 397–415 (2011).
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  2. J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
    [PubMed]
  3. P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
    [Crossref] [PubMed]
  4. M. T. Weigel and M. Dowsett, “Current and emerging biomarkers in breast cancer: prognosis and prediction,” Endocr. Relat. Cancer 17(4), R245–R262 (2010).
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  5. K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
    [Crossref] [PubMed]
  6. S. Achilefu, “Lighting up tumors with receptor-specific optical molecular probes,” Technol. Cancer Res. Treat. 3(4), 393–409 (2004).
    [PubMed]
  7. S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
    [Crossref] [PubMed]
  8. J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6(2), 122–133 (2001).
    [Crossref] [PubMed]
  9. S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35(8), 479–485 (2000).
    [Crossref] [PubMed]
  10. L. Josephson, M. F. Kircher, U. Mahmood, Y. Tang, and R. Weissleder, “Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes,” Bioconjug. Chem. 13(3), 554–560 (2002).
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  11. F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
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  20. C. Tang, P. J. Russell, R. Martiniello-Wilks, J. E. Rasko, and A. Khatri, “Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?” Stem Cells 28(9), 1686–1702 (2010).
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  29. S. L. Schor, “Cell proliferation and migration on collagen substrata in vitro,” J. Cell Sci. 41, 159–175 (1980).
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    [Crossref] [PubMed]
  34. M. R. Lugo and F. J. Sharom, “Interaction of LDS-751 with P-glycoprotein and mapping of the location of the R drug binding site,” Biochemistry 44(2), 643–655 (2005).
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    [Crossref] [PubMed]

2011 (4)

M. Solomon, Y. Liu, M. Y. Berezin, and S. Achilefu, “Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring,” Med. Princ. Pract. 20(5), 397–415 (2011).
[Crossref] [PubMed]

F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
[Crossref] [PubMed]

C. G. Hadjipanayis, H. Jiang, D. W. Roberts, and L. Yang, “Current and future clinical applications for optical imaging of cancer: from intraoperative surgical guidance to cancer screening,” Semin. Oncol. 38(1), 109–118 (2011).
[Crossref] [PubMed]

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

2010 (5)

C. Tang, P. J. Russell, R. Martiniello-Wilks, J. E. Rasko, and A. Khatri, “Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?” Stem Cells 28(9), 1686–1702 (2010).
[Crossref] [PubMed]

A. Rebane, M. A. Drobizhev, N. S. Makarov, E. Beuerman, C. Nacke, and J. Pahapill, “Modeling non-Lorentzian two-photon absprption line shape in dipolar chromophores,” J. Lumin. 130(6), 1055–1059 (2010).
[Crossref]

N. Almog, “Molecular mechanisms underlying tumor dormancy,” Cancer Lett. 294(2), 139–146 (2010).
[Crossref] [PubMed]

M. T. Weigel and M. Dowsett, “Current and emerging biomarkers in breast cancer: prognosis and prediction,” Endocr. Relat. Cancer 17(4), R245–R262 (2010).
[Crossref] [PubMed]

S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
[Crossref] [PubMed]

2009 (3)

P. O. Brown and C. Palmer, “The preclinical natural history of serous ovarian cancer: defining the target for early detection,” PLoS Med. 6(7), e1000114 (2009).
[Crossref] [PubMed]

H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

2008 (3)

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

N. S. Makarov, E. Beuerman, M. Drobizhev, J. Starkey, and A. Rebane, “Environment-sensitive two-photon dye,” Proc. SPIE 7049, 70490Y (2008).
[Crossref]

N. S. Makarov, M. Drobizhev, and A. Rebane, “Two-photon absorption standards in the 550-1600 nm excitation wavelength range,” Opt. Express 16(6), 4029–4047 (2008).
[Crossref] [PubMed]

2007 (1)

R. Ramadass and J. Bereiter-Hahn, ““Photophysical properties of DASPMI as revealed by spectrally resolved fluorescence decays,” J. Phys. B 111(26), 7681–7690 (2007).
[Crossref]

2006 (2)

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
[Crossref] [PubMed]

P. D. Eckford and F. J. Sharom, “P-glycoprotein (ABCB1) interacts directly with lipid-based anti-cancer drugs and platelet-activating factors,” Biochem. Cell Biol. 84(6), 1022–1033 (2006).
[Crossref] [PubMed]

2005 (2)

M. R. Lugo and F. J. Sharom, “Interaction of LDS-751 with P-glycoprotein and mapping of the location of the R drug binding site,” Biochemistry 44(2), 643–655 (2005).
[Crossref] [PubMed]

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
[Crossref] [PubMed]

2004 (1)

S. Achilefu, “Lighting up tumors with receptor-specific optical molecular probes,” Technol. Cancer Res. Treat. 3(4), 393–409 (2004).
[PubMed]

2003 (1)

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

2002 (1)

L. Josephson, M. F. Kircher, U. Mahmood, Y. Tang, and R. Weissleder, “Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes,” Bioconjug. Chem. 13(3), 554–560 (2002).
[Crossref] [PubMed]

2001 (2)

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
[Crossref] [PubMed]

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6(2), 122–133 (2001).
[Crossref] [PubMed]

2000 (1)

S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35(8), 479–485 (2000).
[Crossref] [PubMed]

1989 (1)

N. P. Robertson, J. R. Starkey, S. Hamner, and G. G. Meadows, “Tumor cell invasion of three-dimensional matrices of defined composition: evidence for a specific role for heparan sulfate in rodent cell lines,” Cancer Res. 49(7), 1816–1823 (1989).
[PubMed]

1988 (1)

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

1986 (1)

W. Jones and H. L. Hosick, “Collagen concentration as a significant variable for growth and morphology of mouse mammary parenchyma in collagen matrix culture,” Cell Biol. Int. Rep. 10(4), 277–286 (1986).
[Crossref] [PubMed]

1981 (2)

H. Birkedal-Hansen and K. Danø, “A sensitive collagenase assay using [3H] collagen labeled by reaction with pyridoxal phosphate and [3H] borohydride,” Anal. Biochem. 115(1), 18–26 (1981).
[Crossref] [PubMed]

L. W. Anderson, K. G. Danielson, and H. L. Hosick, “Metastatic potential of hyperplastic alveolar nodule derived mouse mammary tumor cells following intravenous inoculation,” Eur. J. Cancer Clin. Oncol. 17(9), 1001–1008 (1981).
[Crossref] [PubMed]

1980 (2)

S. L. Schor, “Cell proliferation and migration on collagen substrata in vitro,” J. Cell Sci. 41, 159–175 (1980).
[PubMed]

K. G. Danielson, L. W. Anderson, and H. L. Hosick, “Selection and characterization in culture of mammary tumor cells with distinctive growth properties in vivo,” Cancer Res. 40(6), 1812–1819 (1980).
[PubMed]

1974 (1)

R. B. Owens, H. S. Smith, and A. J. Hackett, “Epithelial cell cultures from normal glandular tissue of mice,” J. Natl. Cancer Inst. 53(1), 261–269 (1974).
[PubMed]

Achilefu, S.

M. Solomon, Y. Liu, M. Y. Berezin, and S. Achilefu, “Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring,” Med. Princ. Pract. 20(5), 397–415 (2011).
[Crossref] [PubMed]

S. Achilefu, “Lighting up tumors with receptor-specific optical molecular probes,” Technol. Cancer Res. Treat. 3(4), 393–409 (2004).
[PubMed]

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6(2), 122–133 (2001).
[Crossref] [PubMed]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35(8), 479–485 (2000).
[Crossref] [PubMed]

Adams, D. M.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Adrada, B. E.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Adusumilli, P. S.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
[Crossref] [PubMed]

Affuso, A.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Almog, N.

N. Almog, “Molecular mechanisms underlying tumor dormancy,” Cancer Lett. 294(2), 139–146 (2010).
[Crossref] [PubMed]

Anderson, L. W.

L. W. Anderson, K. G. Danielson, and H. L. Hosick, “Metastatic potential of hyperplastic alveolar nodule derived mouse mammary tumor cells following intravenous inoculation,” Eur. J. Cancer Clin. Oncol. 17(9), 1001–1008 (1981).
[Crossref] [PubMed]

K. G. Danielson, L. W. Anderson, and H. L. Hosick, “Selection and characterization in culture of mammary tumor cells with distinctive growth properties in vivo,” Cancer Res. 40(6), 1812–1819 (1980).
[PubMed]

Andrighetto, S.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

Arribas, E.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Ashizawa, K.

H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

Balanda, A. O.

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
[Crossref] [PubMed]

Bandi, G.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

Barth, R. F.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Bauer, M.

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
[Crossref] [PubMed]

Becker, A.

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
[Crossref] [PubMed]

Bellomi, M.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
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Ben-Porat, L.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
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R. Ramadass and J. Bereiter-Hahn, ““Photophysical properties of DASPMI as revealed by spectrally resolved fluorescence decays,” J. Phys. B 111(26), 7681–7690 (2007).
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Berezin, M. Y.

M. Solomon, Y. Liu, M. Y. Berezin, and S. Achilefu, “Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring,” Med. Princ. Pract. 20(5), 397–415 (2011).
[Crossref] [PubMed]

Beuerman, E.

A. Rebane, M. A. Drobizhev, N. S. Makarov, E. Beuerman, C. Nacke, and J. Pahapill, “Modeling non-Lorentzian two-photon absprption line shape in dipolar chromophores,” J. Lumin. 130(6), 1055–1059 (2010).
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N. S. Makarov, E. Beuerman, M. Drobizhev, J. Starkey, and A. Rebane, “Environment-sensitive two-photon dye,” Proc. SPIE 7049, 70490Y (2008).
[Crossref]

Birkedal-Hansen, H.

H. Birkedal-Hansen and K. Danø, “A sensitive collagenase assay using [3H] collagen labeled by reaction with pyridoxal phosphate and [3H] borohydride,” Anal. Biochem. 115(1), 18–26 (1981).
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Bozzini, A.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
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P. O. Brown and C. Palmer, “The preclinical natural history of serous ovarian cancer: defining the target for early detection,” PLoS Med. 6(7), e1000114 (2009).
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Brunetti, A.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Bucci, D. M.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Bugaj, J. E.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6(2), 122–133 (2001).
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S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35(8), 479–485 (2000).
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N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
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Cassano, E.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

Cerussi, A. E.

S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
[Crossref] [PubMed]

Chan, M. K.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
[Crossref] [PubMed]

Chuang, H. H.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Chun, Y. S.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
[Crossref] [PubMed]

Danielson, K. G.

L. W. Anderson, K. G. Danielson, and H. L. Hosick, “Metastatic potential of hyperplastic alveolar nodule derived mouse mammary tumor cells following intravenous inoculation,” Eur. J. Cancer Clin. Oncol. 17(9), 1001–1008 (1981).
[Crossref] [PubMed]

K. G. Danielson, L. W. Anderson, and H. L. Hosick, “Selection and characterization in culture of mammary tumor cells with distinctive growth properties in vivo,” Cancer Res. 40(6), 1812–1819 (1980).
[PubMed]

Danø, K.

H. Birkedal-Hansen and K. Danø, “A sensitive collagenase assay using [3H] collagen labeled by reaction with pyridoxal phosphate and [3H] borohydride,” Anal. Biochem. 115(1), 18–26 (1981).
[Crossref] [PubMed]

DeNovo, R. C.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Dmytruk, I. M.

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
[Crossref] [PubMed]

Dorshow, R. B.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6(2), 122–133 (2001).
[Crossref] [PubMed]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35(8), 479–485 (2000).
[Crossref] [PubMed]

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M. T. Weigel and M. Dowsett, “Current and emerging biomarkers in breast cancer: prognosis and prediction,” Endocr. Relat. Cancer 17(4), R245–R262 (2010).
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N. S. Makarov, M. Drobizhev, and A. Rebane, “Two-photon absorption standards in the 550-1600 nm excitation wavelength range,” Opt. Express 16(6), 4029–4047 (2008).
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N. S. Makarov, E. Beuerman, M. Drobizhev, J. Starkey, and A. Rebane, “Environment-sensitive two-photon dye,” Proc. SPIE 7049, 70490Y (2008).
[Crossref]

Drobizhev, M. A.

A. Rebane, M. A. Drobizhev, N. S. Makarov, E. Beuerman, C. Nacke, and J. Pahapill, “Modeling non-Lorentzian two-photon absprption line shape in dipolar chromophores,” J. Lumin. 130(6), 1055–1059 (2010).
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P. D. Eckford and F. J. Sharom, “P-glycoprotein (ABCB1) interacts directly with lipid-based anti-cancer drugs and platelet-activating factors,” Biochem. Cell Biol. 84(6), 1022–1033 (2006).
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Ehlis, A. C.

F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
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Eisenberg, D. P.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
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Fallgatter, A. J.

F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
[Crossref] [PubMed]

Fong, Y.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
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Fukushima, A.

H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
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H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

Galak, M. P.

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
[Crossref] [PubMed]

Gratton, E.

S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
[Crossref] [PubMed]

Greco, A.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
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C. G. Hadjipanayis, H. Jiang, D. W. Roberts, and L. Yang, “Current and future clinical applications for optical imaging of cancer: from intraoperative surgical guidance to cancer screening,” Semin. Oncol. 38(1), 109–118 (2011).
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Haeussinger, F. B.

F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
[Crossref] [PubMed]

Hahn, T.

F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
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H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

Hayashi, K.

H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

Heinzel, S.

F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
[Crossref] [PubMed]

Hendershott, K. J.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
[Crossref] [PubMed]

Henklein, P.

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
[Crossref] [PubMed]

Hessenius, C.

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
[Crossref] [PubMed]

Hinkle, G. H.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Honda, S.

H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

Hosick, H. L.

W. Jones and H. L. Hosick, “Collagen concentration as a significant variable for growth and morphology of mouse mammary parenchyma in collagen matrix culture,” Cell Biol. Int. Rep. 10(4), 277–286 (1986).
[Crossref] [PubMed]

L. W. Anderson, K. G. Danielson, and H. L. Hosick, “Metastatic potential of hyperplastic alveolar nodule derived mouse mammary tumor cells following intravenous inoculation,” Eur. J. Cancer Clin. Oncol. 17(9), 1001–1008 (1981).
[Crossref] [PubMed]

K. G. Danielson, L. W. Anderson, and H. L. Hosick, “Selection and characterization in culture of mammary tumor cells with distinctive growth properties in vivo,” Cancer Res. 40(6), 1812–1819 (1980).
[PubMed]

Hsiang, D.

S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
[Crossref] [PubMed]

Huq, R.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
[Crossref] [PubMed]

Jagannathan, R.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Jewell, S.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Jiang, H.

C. G. Hadjipanayis, H. Jiang, D. W. Roberts, and L. Yang, “Current and future clinical applications for optical imaging of cancer: from intraoperative surgical guidance to cancer screening,” Semin. Oncol. 38(1), 109–118 (2011).
[Crossref] [PubMed]

Jones, W.

W. Jones and H. L. Hosick, “Collagen concentration as a significant variable for growth and morphology of mouse mammary parenchyma in collagen matrix culture,” Cell Biol. Int. Rep. 10(4), 277–286 (1986).
[Crossref] [PubMed]

Josephson, L.

L. Josephson, M. F. Kircher, U. Mahmood, Y. Tang, and R. Weissleder, “Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes,” Bioconjug. Chem. 13(3), 554–560 (2002).
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Kasili, P. M.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
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Khatri, A.

C. Tang, P. J. Russell, R. Martiniello-Wilks, J. E. Rasko, and A. Khatri, “Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?” Stem Cells 28(9), 1686–1702 (2010).
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Kircher, M. F.

L. Josephson, M. F. Kircher, U. Mahmood, Y. Tang, and R. Weissleder, “Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes,” Bioconjug. Chem. 13(3), 554–560 (2002).
[Crossref] [PubMed]

Kovalska, V. B.

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
[Crossref] [PubMed]

Kryvorotenko, D. V.

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
[Crossref] [PubMed]

Kukreti, S.

S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
[Crossref] [PubMed]

Lee, R. J.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Licha, K.

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
[Crossref] [PubMed]

Liu, Y.

M. Solomon, Y. Liu, M. Y. Berezin, and S. Achilefu, “Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring,” Med. Princ. Pract. 20(5), 397–415 (2011).
[Crossref] [PubMed]

Liuzzi, R.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Losytskyy, M. Y.

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
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M. R. Lugo and F. J. Sharom, “Interaction of LDS-751 with P-glycoprotein and mapping of the location of the R drug binding site,” Biochemistry 44(2), 643–655 (2005).
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Mahmood, U.

L. Josephson, M. F. Kircher, U. Mahmood, Y. Tang, and R. Weissleder, “Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes,” Bioconjug. Chem. 13(3), 554–560 (2002).
[Crossref] [PubMed]

Makarov, N. S.

A. Rebane, M. A. Drobizhev, N. S. Makarov, E. Beuerman, C. Nacke, and J. Pahapill, “Modeling non-Lorentzian two-photon absprption line shape in dipolar chromophores,” J. Lumin. 130(6), 1055–1059 (2010).
[Crossref]

N. S. Makarov, M. Drobizhev, and A. Rebane, “Two-photon absorption standards in the 550-1600 nm excitation wavelength range,” Opt. Express 16(6), 4029–4047 (2008).
[Crossref] [PubMed]

N. S. Makarov, E. Beuerman, M. Drobizhev, J. Starkey, and A. Rebane, “Environment-sensitive two-photon dye,” Proc. SPIE 7049, 70490Y (2008).
[Crossref]

Mancini, M.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Martin, E. W.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Martiniello-Wilks, R.

C. Tang, P. J. Russell, R. Martiniello-Wilks, J. E. Rasko, and A. Khatri, “Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?” Stem Cells 28(9), 1686–1702 (2010).
[Crossref] [PubMed]

Mawlawi, O. R.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Meadows, G. G.

N. P. Robertson, J. R. Starkey, S. Hamner, and G. G. Meadows, “Tumor cell invasion of three-dimensional matrices of defined composition: evidence for a specific role for heparan sulfate in rodent cell lines,” Cancer Res. 49(7), 1816–1823 (1989).
[PubMed]

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A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

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A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

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H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

Mojzisik, C. M.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Nacke, C.

A. Rebane, M. A. Drobizhev, N. S. Makarov, E. Beuerman, C. Nacke, and J. Pahapill, “Modeling non-Lorentzian two-photon absprption line shape in dipolar chromophores,” J. Lumin. 130(6), 1055–1059 (2010).
[Crossref]

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O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Overholt, B. F.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Owens, R. B.

R. B. Owens, H. S. Smith, and A. J. Hackett, “Epithelial cell cultures from normal glandular tissue of mice,” J. Natl. Cancer Inst. 53(1), 261–269 (1974).
[PubMed]

Pahapill, J.

A. Rebane, M. A. Drobizhev, N. S. Makarov, E. Beuerman, C. Nacke, and J. Pahapill, “Modeling non-Lorentzian two-photon absprption line shape in dipolar chromophores,” J. Lumin. 130(6), 1055–1059 (2010).
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P. O. Brown and C. Palmer, “The preclinical natural history of serous ovarian cancer: defining the target for early detection,” PLoS Med. 6(7), e1000114 (2009).
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J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Panjehpour, M.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Phan, M. N.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

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V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
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J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, “Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform,” J. Biomed. Opt. 6(2), 122–133 (2001).
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R. Ramadass and J. Bereiter-Hahn, ““Photophysical properties of DASPMI as revealed by spectrally resolved fluorescence decays,” J. Phys. B 111(26), 7681–7690 (2007).
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Rasko, J. E.

C. Tang, P. J. Russell, R. Martiniello-Wilks, J. E. Rasko, and A. Khatri, “Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?” Stem Cells 28(9), 1686–1702 (2010).
[Crossref] [PubMed]

Rebane, A.

A. Rebane, M. A. Drobizhev, N. S. Makarov, E. Beuerman, C. Nacke, and J. Pahapill, “Modeling non-Lorentzian two-photon absprption line shape in dipolar chromophores,” J. Lumin. 130(6), 1055–1059 (2010).
[Crossref]

N. S. Makarov, E. Beuerman, M. Drobizhev, J. Starkey, and A. Rebane, “Environment-sensitive two-photon dye,” Proc. SPIE 7049, 70490Y (2008).
[Crossref]

N. S. Makarov, M. Drobizhev, and A. Rebane, “Two-photon absorption standards in the 550-1600 nm excitation wavelength range,” Opt. Express 16(6), 4029–4047 (2008).
[Crossref] [PubMed]

Renne, G.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

Riedl, C. C.

P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
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Roberts, D. W.

C. G. Hadjipanayis, H. Jiang, D. W. Roberts, and L. Yang, “Current and future clinical applications for optical imaging of cancer: from intraoperative surgical guidance to cancer screening,” Semin. Oncol. 38(1), 109–118 (2011).
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Robertson, N. P.

N. P. Robertson, J. R. Starkey, S. Hamner, and G. G. Meadows, “Tumor cell invasion of three-dimensional matrices of defined composition: evidence for a specific role for heparan sulfate in rodent cell lines,” Cancer Res. 49(7), 1816–1823 (1989).
[PubMed]

Rohren, E. M.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
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Russell, P. J.

C. Tang, P. J. Russell, R. Martiniello-Wilks, J. E. Rasko, and A. Khatri, “Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?” Stem Cells 28(9), 1686–1702 (2010).
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P. S. Adusumilli, D. P. Eisenberg, Y. S. Chun, K. W. Ryu, L. Ben-Porat, K. J. Hendershott, M. K. Chan, R. Huq, C. C. Riedl, and Y. Fong, “Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery,” J. Gastrointest. Surg. 9(8), 1138–1147 (2005).
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Salerno, P.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
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Salvatore, G.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
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M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Santiago, L.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Santoro, M.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Santos, G.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

Sautins, I.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Schecklmann, M.

F. B. Haeussinger, S. Heinzel, T. Hahn, M. Schecklmann, A. C. Ehlis, and A. J. Fallgatter, “Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging,” PLoS ONE 6(10), e26377 (2011).
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M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Semmler, W.

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
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Sharom, F. J.

P. D. Eckford and F. J. Sharom, “P-glycoprotein (ABCB1) interacts directly with lipid-based anti-cancer drugs and platelet-activating factors,” Biochem. Cell Biol. 84(6), 1022–1033 (2006).
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M. R. Lugo and F. J. Sharom, “Interaction of LDS-751 with P-glycoprotein and mapping of the location of the R drug binding site,” Biochemistry 44(2), 643–655 (2005).
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Shkumat, N. A.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Smith, H. S.

R. B. Owens, H. S. Smith, and A. J. Hackett, “Epithelial cell cultures from normal glandular tissue of mice,” J. Natl. Cancer Inst. 53(1), 261–269 (1974).
[PubMed]

Solomon, M.

M. Solomon, Y. Liu, M. Y. Berezin, and S. Achilefu, “Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring,” Med. Princ. Pract. 20(5), 397–415 (2011).
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Song, J. M.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Springer, A.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Starkey, J.

N. S. Makarov, E. Beuerman, M. Drobizhev, J. Starkey, and A. Rebane, “Environment-sensitive two-photon dye,” Proc. SPIE 7049, 70490Y (2008).
[Crossref]

Starkey, J. R.

N. P. Robertson, J. R. Starkey, S. Hamner, and G. G. Meadows, “Tumor cell invasion of three-dimensional matrices of defined composition: evidence for a specific role for heparan sulfate in rodent cell lines,” Cancer Res. 49(7), 1816–1823 (1989).
[PubMed]

Steplewski, Z.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Stokes, D. L.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Tanamai, W.

S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
[Crossref] [PubMed]

Tang, C.

C. Tang, P. J. Russell, R. Martiniello-Wilks, J. E. Rasko, and A. Khatri, “Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?” Stem Cells 28(9), 1686–1702 (2010).
[Crossref] [PubMed]

Tang, Y.

L. Josephson, M. F. Kircher, U. Mahmood, Y. Tang, and R. Weissleder, “Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes,” Bioconjug. Chem. 13(3), 554–560 (2002).
[Crossref] [PubMed]

Thurston, M. O.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Tokar, V. P.

V. P. Tokar, M. Y. Losytskyy, V. B. Kovalska, D. V. Kryvorotenko, A. O. Balanda, V. M. Prokopets, M. P. Galak, I. M. Dmytruk, V. M. Yashchuk, and S. M. Yarmoluk, “Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon excitation,” J. Fluoresc. 16(6), 783–791 (2006).
[Crossref] [PubMed]

Tromberg, B. J.

S. Kukreti, A. E. Cerussi, W. Tanamai, D. Hsiang, B. J. Tromberg, and E. Gratton, “Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy,” Radiology 254(1), 277–284 (2010).
[Crossref] [PubMed]

Troncone, G.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Tuttle, S. E.

O. A. Oredipe, R. F. Barth, S. E. Tuttle, D. M. Adams, I. Sautins, D. M. Bucci, C. M. Mojzisik, G. H. Hinkle, S. Jewell, Z. Steplewski, M. O. Thurston, and E. W. Martin, “Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe” Int. J. Rad. Appl. Instrum. Part B. Nucl. Med. Biol. 15, 595–603 (1988).

Uetani, M.

H. Hayashi, K. Ashizawa, M. Uetani, S. Futagawa, A. Fukushima, K. Minami, S. Honda, and K. Hayashi, “Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity,” Br. J. Radiol. 82(976), 272–278 (2009).
[Crossref] [PubMed]

Vento, A. R.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

Vergara, E.

M. Mancini, E. Vergara, G. Salvatore, A. Greco, G. Troncone, A. Affuso, R. Liuzzi, P. Salerno, M. Scotto di Santolo, M. Santoro, A. Brunetti, and M. Salvatore, “Morphological ultrasound microimaging of thyroid in living mice,” Endocrinology 150(10), 4810–4815 (2009).
[Crossref] [PubMed]

Viale, G.

A. Bozzini, G. Renne, L. Meneghetti, G. Bandi, G. Santos, A. R. Vento, S. Menna, S. Andrighetto, G. Viale, E. Cassano, and M. Bellomi, “Sensitivity of imaging for multifocal-multicentric breast carcinoma,” BMC Cancer 8(1), 275 (2008).
[Crossref] [PubMed]

Vo-Dinh, T.

J. M. Song, R. Jagannathan, D. L. Stokes, P. M. Kasili, M. Panjehpour, M. N. Phan, B. F. Overholt, R. C. DeNovo, X. Pan, R. J. Lee, and T. Vo-Dinh, “Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis,” Technol. Cancer Res. Treat. 2(6), 515–523 (2003).
[PubMed]

Walker, C. M.

N. A. Shkumat, A. Springer, C. M. Walker, E. M. Rohren, W. T. Yang, B. E. Adrada, E. Arribas, S. Carkaci, H. H. Chuang, L. Santiago, and O. R. Mawlawi, “Investigating the limit of detectability of a positron emission mammography device: a phantom study,” Med. Phys. 38(9), 5176–5185 (2011).
[Crossref] [PubMed]

Weigel, M. T.

M. T. Weigel and M. Dowsett, “Current and emerging biomarkers in breast cancer: prognosis and prediction,” Endocr. Relat. Cancer 17(4), R245–R262 (2010).
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Weissleder, R.

L. Josephson, M. F. Kircher, U. Mahmood, Y. Tang, and R. Weissleder, “Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes,” Bioconjug. Chem. 13(3), 554–560 (2002).
[Crossref] [PubMed]

Wiedenmann, B.

K. Licha, C. Hessenius, A. Becker, P. Henklein, M. Bauer, S. Wisniewski, B. Wiedenmann, and W. Semmler, “Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes,” Bioconjug. Chem. 12(1), 44–50 (2001).
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Figures (7)

Fig. 1
Fig. 1 Properties of the tissue phantoms. (a) General view of a collagen type I based phantom consisting of collagen matrix (lower half) and serum medium containing Styryl-9M (upper half); (b) a normal mouse mammary epithelial cell colony in a phantom after 2 days of incubation; (c) high magnification image of normal mouse mammary epithelial cell colony after 14 days of incubation.

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Fig. 2
Fig. 2 Schematic of the imaging setup. ND, variable neutral density filter; ID, iris diaphragm; L1, focusing lens; OB, imaging objective (camera lens or microscope objective); SF, spectral filter; CCD, imaging detector. Inserts show the mouse ear tumor (a) and the near-IR laser spot (b); 2PEF in a dye-doped plastic film positioned in front of the tumor visualizes the laser beam.

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Fig. 3
Fig. 3 (a) 2PA spectrum of Styryl-9M in chloroform (black line), shown as 2PA cross section (left y-axis) versus laser wavelength (bottom x-axis). 1PA extinction spectrum (blue dotted line) and fluorescence emission spectrum (red line) in chloroform; (b) 2PEF spectra in tissue phantoms with no cells (black squares), with normal cells (red circles), and with cancer cells (blue triangles), all normalized at 1100 nm and presented in arbitrary units.

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Fig. 4
Fig. 4 Dependence of the fluorescence intensity ratio (2) on the x-distance across the phantom. (a) Homogeneous phantoms with uniform distribution of the cells throughout the collagen matrix. The coding of the colony types is shown in the inset. (b) Phantoms containing, in addition to normal cells, a single implanted colony of cancer cells. Distance is measured from the center of the phantom. Vertical dashed lines indicate approximate margins of the initially implanted cancer colony. The laser beam had a symmetrical Gaussian spatial profile with FWHM of ~200 μm. The excitation beam propagates from right to left.

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Fig. 5
Fig. 5 Estimation of the smallest number of cancer cells that can be detected as a colony in the phantom. Horizontal axes – estimated number of cancer cells in the implanted colony; Horizontal dotted line indicates the empirical threshold for the discrimination between the cancer-containing and cancer-free samples; (a) +SA cancer line. Solid curve: fit parameters used, FU = 0.55, FB = 0.95, N = 106, NPgp = 40,000 and ΔE/kT = 16.0; (b) NIHOVCAR3 cancer line.

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Fig. 6
Fig. 6 Fluorescence image of 4T1 cells stained with anti p-glycoprotein antibody and Alexa Fluor 568 protein A.

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Fig. 7
Fig. 7 Dual wavelength 2PEF imaging of the pinna of the mouse ear with the laser beam perpendicular to the pinna. Panels (a) and (c) show the image and the integrated intensity trace for an apparently normal region of the pinna of the ear; Panels (b) and (d) show the same for a region containing the 4T1 tumor.

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Tables (3)

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Table 1 Primers used in the real time PCR analysis

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Table 3 PCR expression analysis for MDR1 proteins

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Table 2 Relative fluorescence for MDR1

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Equations (8)

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F( x i , y j )= I 1200 ( x i , y j ) I 1100 ( x i , y j ) .
F ˜ ( x i )= I 1200 ( x i )− I B ( x i ) I 1100 ( x i )− I B ( x i ) ( P 1100 P 1200 ) 2 ,
I( x i )= ∑ j=1 M I( x i , y j ) ,
F= σ 2 B ( 1200 ) ϕ B N B + σ 2 U ( 1200 ) ϕ U N U σ 2 U ( 1100 ) ϕ B N B + σ 2 U ( 1100 ) ϕ U N U ,
σ 2 B ( 1100 ) ϕ B = σ 2 U ( 1100 ) ϕ U .
F= σ 2 U ( 1200 ) σ 2 U ( 1100 ) + N B N ( σ 2 B ( 1200 ) σ 2 B ( 1100 ) − σ 2 U ( 1200 ) σ 2 U ( 1100 ) ),
e − ΔE kT = N B ( N− N B )( N Pgp N c − N B ) ,
F( N c )= F U +( F B − F U ) 1+(N+ N ¯ Pgp N c ) e − ΔE kT − [1+(N+ N ¯ Pgp N c ) e − ΔE kT ] 2 −4N N ¯ Pgp N c e − 2ΔE kT 2N e − ΔE kT ,

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