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Tumor detection using folate receptor-targeted imaging agents

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Abstract

Folate receptors are up-regulated on a variety of human cancers, including cancers of the breast, ovaries, endometrium, lungs, kidneys, colon, brain, and myeloid cells of hematopoietic origin. This over-expression of folate receptors (FR) on cancer tissues can be exploited to target folate-linked imaging and therapeutic agents specifically to FR-expressing tumors, thereby avoiding uptake by most healthy tissues that express few if any FR. Four folate-targeted therapeutic drugs are currently undergoing clinical trials, and several folate-linked chemotherapeutic agents are in late stage preclinical development. However, because not all cancers express FR, and because only FR-expressing cancers respond to FR-targeted therapies, FR-targeted imaging agents have been required to select patients with FR-expressing tumors likely to respond to folate-targeted therapies. This review focuses on recent advances in the use of the vitamin folic acid to target PET agents, γ-emitters, MRI contrast agents and fluorescent dyes to FR+ cancers for the purpose of diagnosing and imaging malignant masses with improved specificity and sensitivity.

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References

  1. Bettio, A., Honer, M., Muller, C., Bruhlmeier, M., Muller, U., Schibli, R., et al. (2006). Synthesis and preclinical evaluation of a folic acid derivative labeled with 18F for PET imaging of folate receptor-positive tumors. Journal of Nuclear Medicine, 47, 1153–1160.

    PubMed  CAS  Google Scholar 

  2. Breeman, W. A., Kwekkeboom, D. J., de Blois, E., de Jong, M., Visser, T. J., & Krenning, E. P. (2007). Radiolabelled regulatory peptides for imaging and therapy. Anticancer Agents in Medicinal Chemistry, 7, 345–357.

    Article  CAS  Google Scholar 

  3. Gabriel, M., Decristoforo, C., Kendler, D., Dobrozemsky, G., Heute, D., Uprimny, C., et al. (2007). 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. Journal of Nuclear Medicine, 48, 508–518.

    Article  PubMed  CAS  Google Scholar 

  4. Grotzinger, C., & Wiedenmann, B. (2004). Somatostatin receptor targeting for tumor imaging and therapy. Annals of the New York Academy of Sciences, 1014, 258–264.

    Article  PubMed  CAS  Google Scholar 

  5. Breeman, W. A., de Jong, M., Kwekkeboom, D. J., Valkema, R., Bakker, W. H., Kooij, P. P., et al. (2001). Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives. European Journal of Nuclear Medicine, 28, 1421–1429.

    Article  PubMed  CAS  Google Scholar 

  6. Smith, C. J., Volkert, W. A., & Hoffman, T. J. (2005). Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes. Nuclear Medicine and Biology, 32, 733–740.

    Article  PubMed  CAS  Google Scholar 

  7. Prasanphanich, A. F., Nanda, P. K., Rold, T. L., Ma, L., Lewis, M. R., Garrison, J. C., et al. (2007). [64Cu-NOTA-8-Aoc-BBN(7–14)NH2] targeting vector for positron-emission tomography imaging of gastrin-releasing peptide receptor-expressing tissues. Proceedings of the National Academy of Sciences of the United States of America, 104, 12462–12467.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang, X., Cai, W., Cao, F., Schreibmann, E., Wu, Y., Wu, J. C., et al. (2006). 18F-labeled bombesin analogs for targeting GRP receptor-expressing prostate cancer. Journal of Nuclear Medicine, 47, 492–501.

    PubMed  CAS  Google Scholar 

  9. Leuschner, C., Kumar, C. S., Hansel, W., Soboyejo, W., Zhou, J., & Hormes, J. (2006). LHRH-conjugated magnetic iron oxide nanoparticles for detection of breast cancer metastases. Breast Cancer Research and Treatment, 99, 163–176.

    Article  PubMed  CAS  Google Scholar 

  10. Cai, W., Chen, K., He, L., Cao, Q., Koong, A., & Chen, X. (2007). Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody. European Journal of Nuclear Medicine and Molecular Imaging, 34, 850–858.

    Article  PubMed  CAS  Google Scholar 

  11. Perik, P. J., Lub-De Hooge, M. N., Gietema, J. A., van der Graaf, W. T., de Korte, M. A., Jonkman, S., et al. (2006). Indium-111-labeled trastuzumab scintigraphy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. Journal of Clinical Oncology, 24, 2276–2282.

    Article  PubMed  CAS  Google Scholar 

  12. Reilly, R. M., Kiarash, R., Sandhu, J., Lee, Y. W., Cameron, R. G., Hendler, A., et al. (2000). A comparison of EGF and MAb 528 labeled with 111In for imaging human breast cancer. Journal of Nuclear Medicine, 41, 903–911.

    PubMed  CAS  Google Scholar 

  13. Nagengast, W. B., de Vries, E. G., Hospers, G. A., Mulder, N. H., de Jong, J. R., Hollema, H., et al. (2007). In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. Journal of Nuclear Medicine, 48, 1313–1319.

    Article  PubMed  CAS  Google Scholar 

  14. Cai, W., & Chen, X. (2007). Multimodality imaging of vascular endothelial growth factor and vascular endothelial growth factor receptor expression. Frontiers in Bioscience, 12, 4267–4279.

    Article  PubMed  CAS  Google Scholar 

  15. Low, P. S., Henne, W. A., & Doorneweerd, D. D. (2008). Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Accounts of Chemical Research, 41(1), 120–129.

    Article  PubMed  CAS  Google Scholar 

  16. Reddy, J. A., Allagadda, V. M., & Leamon, C. P. (2005). Targeting therapeutic and imaging agents to folate receptor positive tumors. Current Pharmaceutical Biotechnology, 6, 131–150.

    Article  PubMed  CAS  Google Scholar 

  17. Hilgenbrink, A. R., & Low, P. S. (2005). Folate receptor-mediated drug targeting: from therapeutics to diagnostics. Journal of Pharmaceutical Sciences, 94, 2135–2146.

    Article  PubMed  CAS  Google Scholar 

  18. Collins, D. A., Hogenkamp, H. P., & Gebhard, M. W. (1999). Tumor imaging via indium 111-labeled DTPA-adenosylcobalamin. Mayo Clinic Proceedings, 74, 687–691.

    PubMed  CAS  Google Scholar 

  19. Jasanoff, A. (2005). Functional MRI using molecular imaging agents. Trends in Neurosciences, 28, 120–126.

    Article  PubMed  CAS  Google Scholar 

  20. Shen, F., Ross, J. F., Wang, X., & Ratnam, M. (1994). Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry, 33, 1209–1215.

    Article  PubMed  CAS  Google Scholar 

  21. Antony, A. C. (1996). Folate receptors. Annual Review of Nutrition, 16, 501–521.

    Article  PubMed  CAS  Google Scholar 

  22. Coney, L. R., Tomassetti, A., Carayannopoulos, L., Frasca, V., Kamen, B. A., Colnaghi, M. I., et al. (1991). Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Research, 51, 6125–6132.

    PubMed  CAS  Google Scholar 

  23. Campbell, I. G., Jones, T. A., Foulkes, W. D., & Trowsdale, J. (1991). Folate-binding protein is a marker for ovarian cancer. Cancer Research, 51, 5329–5338.

    PubMed  CAS  Google Scholar 

  24. Weitman, S. D., Lark, R. H., Coney, L. R., Fort, D. W., Frasca, V., Zurawski Jr., V. R., et al. (1992). Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer Research, 52, 3396–3401.

    PubMed  CAS  Google Scholar 

  25. Ross, J. F., Chaudhuri, P. K., & Ratnam, M. (1994). Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications. Cancer, 73, 2432–2443.

    Article  PubMed  CAS  Google Scholar 

  26. Mantovani, L. T., Miotti, S., Menard, S., Canevari, S., Raspagliesi, F., Bottini, C., et al. (1994). Folate binding protein distribution in normal tissues and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies MOv18 and MOv19. European Journal of Cancer, 30A, 363–369.

    Article  PubMed  CAS  Google Scholar 

  27. Holm, J., Hansen, S. I., Sondergaard, K., & Hoier-Madsen, M. (1993). Chemistry and biology of pteridines and folates. The high-affinity folate binding protein in normal and malignant mammary gland tissue. New York: Plenum.

    Google Scholar 

  28. Weitman, S. D., Weinberg, A. G., Coney, L. R., Zurawski, V. R., Jennings, D. S., & Kamen, B. A. (1992). Cellular localization of the folate receptor: potential role in drug toxicity and folate homeostasis. Cancer Research, 52, 6708–6711.

    PubMed  CAS  Google Scholar 

  29. Holm, J., Hansen, S. I., Hoier-Madsen, M., & Bostad, L. (1991). High-affinity folate binding in human choroid plexus. Characterization of radioligand binding, immunoreactivity, molecular heterogeneity and hydrophobic domain of the binding protein. Biochemical Journal, 280, 267–271.

    PubMed  CAS  Google Scholar 

  30. Zimmerman, J. (1990). Folic acid transport in organ-cultured mucosa of human intestine. Evidence for distinct carriers. Gastroenterology, 99, 964–972.

    PubMed  CAS  Google Scholar 

  31. Morshed, K. M., Ross, D. M., & McMartin, K. E. (1997). Folate transport proteins mediate the bidirectional transport of 5-methyltetrahydrofolate in cultured human proximal tubule cells. Journal of Nutrition, 127, 1137–1147.

    PubMed  CAS  Google Scholar 

  32. Franklin, W. A., Waintrub, M., Edwards, D., Christensen, K., Prendegrast, P., Woods, J., et al. (1994). New anti-lung-cancer antibody cluster 12 reacts with human folate receptors present on adenocarcinoma. International Journal of Cancer—Supplement, 8, 89–95.

    Article  CAS  Google Scholar 

  33. Holm, J., Hansen, S. I., Hoier-Madsen, M., Helkjaer, P. E., & Nichols, C. W. (1997). Folate receptors in malignant and benign tissues of human female genital tract. Bioscience Reports, 17, 415–427.

    Article  PubMed  CAS  Google Scholar 

  34. Toffoli, G., Cernigoi, C., Russo, A., Gallo, A., Bagnoli, M., & Boiocchi, M. (1997). Overexpression of folate binding protein in ovarian cancers. International Journal of Cancer, 74, 193–198.

    Article  CAS  Google Scholar 

  35. Garin-Chesa, P., Campbell, I., Saigo, P. E., Lewis Jr., J. L., Old, L. J., & Rettig, W. J. (1993). Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. American Journal of Pathology, 142, 557–567.

    PubMed  CAS  Google Scholar 

  36. Boerman, O. C., van Niekerk, C. C., Makkink, K., Hanselaar, T. G., Kenemans, P., & Poels, L. G. (1991). Comparative immunohistochemical study of four monoclonal antibodies directed against ovarian carcinoma-associated antigens. International Journal of Gynecological Pathology, 10, 15–25.

    Article  PubMed  CAS  Google Scholar 

  37. Dainty, L. A., Risinger, J. I., Morrison, C., Chandramouli, G. V., Bidus, M. A., Zahn, C., et al. (2007). Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma. Gynecologic Oncology, 105, 563–570.

    Article  PubMed  CAS  Google Scholar 

  38. Weitman, S. D., Frazier, K. M., & Kamen, B. A. (1994). The folate receptor in central nervous system malignancies of childhood. Journal of Neuro-Oncology, 21, 107–112.

    Article  PubMed  CAS  Google Scholar 

  39. Hartmann, L. C., Keeney, G. L., Lingle, W. L., Christianson, T. J., Varghese, B., Hillman, D., et al. (2007). Folate receptor overexpression is associated with poor outcome in breast cancer. International Journal of Cancer, 121, 938–942.

    Article  CAS  Google Scholar 

  40. Paulos, C. M., Turk, M. J., Breur, G. J., & Low, P. S. (2004). Folate receptor-mediated targeting of therapeutic and imaging agents to activated macrophages in rheumatoid arthritis. Advanced Drug Delivery Reviews, 56, 1205–1217.

    Article  PubMed  CAS  Google Scholar 

  41. Nakashima-Matsushita, N., Homma, T., Yu, S., Matsuda, T., Sunahara, N., Nakamura, T., et al. (1999). Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis and Rheumatism, 42, 1609–1616.

    Article  PubMed  CAS  Google Scholar 

  42. Ross, J. F., Wang, H., Behm, F. G., Mathew, P., Wu, M., Booth, R., et al. (1999). Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia. Cancer, 85, 348–357.

    Article  PubMed  CAS  Google Scholar 

  43. Kamen, B. A., & Smith, A. K. (2004). A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro. Advanced Drug Delivery Reviews, 56, 1085–1097.

    Article  PubMed  CAS  Google Scholar 

  44. Leamon, C. P., & Low, P. S. (1991). Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis. Proceedings of the National Academy of Sciences of the United States of America, 88, 5572–5576.

    Article  PubMed  CAS  Google Scholar 

  45. Turek, J. J., Leamon, C. P., & Low, P. S. (1993). Endocytosis of folate-protein conjugates: ultrastructural localization in KB cells. Journal of Cell Science, 106(Pt 1), 423–430.

    PubMed  CAS  Google Scholar 

  46. Yang, J., Chen, H., Vlahov, I. R., Cheng, J. X., & Low, P. S. (2006). Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging. Proceedings of the National Academy of Sciences of the United States of America, 103, 13872–13877.

    Article  PubMed  CAS  Google Scholar 

  47. Paulos, C. M., Reddy, J. A., Leamon, C. P., Turk, M. J., & Low, P. S. (2004). Ligand binding and kinetics of folate receptor recycling in vivo: impact on receptor-mediated drug delivery. Molecular Pharmacology, 66, 1406–1414.

    Article  PubMed  CAS  Google Scholar 

  48. Leamon, C. P., Parker, M. A., Vlahov, I. R., Xu, L. C., Reddy, J. A., Vetzel, M., et al. (2002). Synthesis and biological evaluation of EC20: a new folate-derived, (99m)Tc-based radiopharmaceutical. Bioconjugate Chemistry, 13, 1200–1210.

    Article  PubMed  CAS  Google Scholar 

  49. Vlashi, E., Sturgis, J., & Low, P. S. Real time, non-invasive and quantitative imaging of the accumulation of ligand-targeted drugs into receptor-expressing solid tumors. in press.

  50. Leamon, C. P., & Low, P. S. (2001). Folate-mediated targeting: from diagnostics to drug and gene delivery. Drug Discovery Today, 6, 44–51.

    Article  PubMed  CAS  Google Scholar 

  51. Leamon, C. P., & Low, P. S. (1992). Cytotoxicity of momordin–folate conjugates in cultured human cells. Journal of Biological Chemistry, 267, 24966–24971.

    PubMed  CAS  Google Scholar 

  52. Atkinson, S. F., Bettinger, T., Seymour, L. W., Behr, J. P., & Ward, C. M. (2001). Conjugation of folate via gelonin carbohydrate residues retains ribosomal-inactivating properties of the toxin and permits targeting to folate receptor positive cells. Journal of Biological Chemistry, 276, 27930–27935.

    Article  PubMed  CAS  Google Scholar 

  53. Leamon, C. P., Reddy, J. A., Vlahov, I. R., Westrick, E., Dawson, A., Dorton, R., et al. (2007). Preclinical antitumor activity of a novel folate-targeted dual drug conjugate. Molecular Pharmaceutics, 4, 659–667.

    Article  PubMed  CAS  Google Scholar 

  54. Reddy, J. A., Dorton, R., Westrick, E., Dawson, A., Smith, T., Xu, L. C., et al. (2007). Preclinical evaluation of EC145, a folate–vinca alkaloid conjugate. Cancer Research, 67, 4434–4442.

    Article  PubMed  CAS  Google Scholar 

  55. Leamon, C. P., Reddy, J. A., Vlahov, I. R., Vetzel, M., Parker, N., Nicoson, J. S., et al. (2005). Synthesis and biological evaluation of EC72: a new folate-targeted chemotherapeutic. Bioconjugate Chemistry, 16, 803–811.

    Article  PubMed  CAS  Google Scholar 

  56. Henne, W. A., Doorneweerd, D. D., Hilgenbrink, A. R., Kularatne, S. A., & Low, P. S. (2006). Synthesis and activity of a folate peptide camptothecin prodrug. Bioorganic & Medicinal Chemistry Letters, 16, 5350–5355.

    Article  CAS  Google Scholar 

  57. Reddy, J. A., & Low, P. S. (2000). Enhanced folate receptor mediated gene therapy using a novel pH-sensitive lipid formulation. Journal of Controlled Release, 64, 27–37.

    Article  PubMed  CAS  Google Scholar 

  58. Xu, L., Pirollo, K. F., Tang, W. H., Rait, A., & Chang, E. H. (1999). Transferrin-liposome-mediated systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts. Human Gene Therapy, 10, 2941–2952.

    Article  PubMed  CAS  Google Scholar 

  59. Zhao, X. B., & Lee, R. J. (2004). Tumor-selective targeted delivery of genes and antisense oligodeoxyribonucleotides via the folate receptor. Advanced Drug Delivery Reviews, 56, 1193–1204.

    Article  PubMed  CAS  Google Scholar 

  60. Pan, X. Q., Zheng, X., Shi, G., Wang, H., Ratnam, M., & Lee, R. J. (2002). Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta-targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid. Blood, 100, 594–602.

    Article  PubMed  CAS  Google Scholar 

  61. Anderson, K. E., Eliot, L. A., Stevenson, B. R., & Rogers, J. A. (2001). Formulation and evaluation of a folic acid receptor-targeted oral vancomycin liposomal dosage form. Pharmaceutical Research, 18, 316–322.

    Article  PubMed  CAS  Google Scholar 

  62. Gabizon, A., Shmeeda, H., Horowitz, A. T., & Zalipsky, S. (2004). Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid–PEG conjugates. Advanced Drug Delivery Reviews, 56, 1177–1192.

    Article  PubMed  CAS  Google Scholar 

  63. Roy, E. J., Gawlick, U., Orr, B. A., & Kranz, D. M. (2004). Folate-mediated targeting of T cells to tumors. Advanced Drug Delivery Reviews, 56, 1219–1231.

    Article  PubMed  CAS  Google Scholar 

  64. Lu, Y., Sega, E., Leamon, C. P., & Low, P. S. (2004). Folate receptor-targeted immunotherapy of cancer: mechanism and therapeutic potential. Advanced Drug Delivery Reviews, 56, 1161–1176.

    Article  PubMed  CAS  Google Scholar 

  65. Lu, Y., & Low, P. S. (2002). Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors. Cancer Immunology and Immunotherapy, 51, 153–162.

    Article  PubMed  CAS  Google Scholar 

  66. Cho, B. K., Roy, E. J., Patrick, T. A., & Kranz, D. M. (1997). Single-chain Fv/folate conjugates mediate efficient lysis of folate-receptor-positive tumor cells. Bioconjugate Chemistry, 8, 338–346.

    Article  PubMed  CAS  Google Scholar 

  67. Quintana, A., Raczka, E., Piehler, L., Lee, I., Myc, A., Majoros, I., et al. (2002). Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharmaceutical Research, 19, 1310–1316.

    Article  PubMed  CAS  Google Scholar 

  68. Lu, J. Y., Lowe, D. A., Kennedy, M. D., & Low, P. S. (1999). Folate-targeted enzyme prodrug cancer therapy utilizing penicillin-V amidase and a doxorubicin prodrug. Journal of Drug Targeting, 7, 43–53.

    PubMed  CAS  Google Scholar 

  69. Low, P. S., & Antony, A. C. (2004). Folate receptor-targeted drugs for cancer and inflammatory diseases. Advanced Drug Delivery Reviews, 56, 1055–1238.

    Article  PubMed  CAS  Google Scholar 

  70. Mathias, C. J., Wang, S., Lee, R. J., Waters, D. J., Low, P. S., & Green, M. A. (1996). Tumor-selective radiopharmaceutical targeting via receptor-mediated endocytosis of gallium-67-deferoxamine-folate. Journal of Nuclear Medicine, 37, 1003–1008.

    PubMed  CAS  Google Scholar 

  71. Mathias, C. J., Wang, S., Waters, D. J., Turek, J. J., Low, P. S., & Green, M. A. (1998). Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical. Journal of Nuclear Medicine, 39, 1579–1585.

    PubMed  CAS  Google Scholar 

  72. Wang, S., Luo, J., Lantrip, D. A., Waters, D. J., Mathias, C. J., Green, M. A., et al. (1997). Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical. Bioconjugate Chemistry, 8, 673–679.

    Article  PubMed  CAS  Google Scholar 

  73. Guo, W., Hinkle, G. H., & Lee, R. J. (1999). 99mTc-HYNIC-folate: a novel receptor-based targeted radiopharmaceutical for tumor imaging. Journal of Nuclear Medicine, 40, 1563–1569.

    PubMed  CAS  Google Scholar 

  74. Ilgan, S., Yang, D. J., Higuchi, T., Zareneyrizi, F., Bayhan, H., Yu, D., et al. (1998). 99mTc-ethylenedicysteine-folate: a new tumor imaging agent. Synthesis, labeling and evaluation in animals. Cancer Biotherapy & Radiopharmaceuticals, 13, 427–435.

    Article  CAS  Google Scholar 

  75. Mathias, C. J., Hubers, D., Low, P. S., & Green, M. A. (2000). Synthesis of [(99m)Tc]DTPA-folate and its evaluation as a folate-receptor-targeted radiopharmaceutical. Bioconjugate Chemistry, 11, 253–257.

    Article  PubMed  CAS  Google Scholar 

  76. Trump, D. P., Mathias, C. J., Yang, Z., Low, P. S., Marmion, M., & Green, M. A. (2002). Synthesis and evaluation of 99mTc(CO)(3)-DTPA-folate as a folate-receptor-targeted radiopharmaceutical. Nuclear Medicine and Biology, 29, 569–573.

    Article  PubMed  CAS  Google Scholar 

  77. Muller, C., Hohn, A., Schubiger, P. A., & Schibli, R. (2006). Preclinical evaluation of novel organometallic 99mTc-folate and 99mTc-pteroate radiotracers for folate receptor-positive tumour targeting. European Journal of Nuclear Medicine and Molecular Imaging, 33, 1007–1016.

    Article  PubMed  CAS  Google Scholar 

  78. Muller, C., Schubiger, P. A., & Schibli, R. (2006). In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel 99mTc-radiofolate tracer. European Journal of Nuclear Medicine and Molecular Imaging, 33, 1162–1170.

    Article  PubMed  CAS  Google Scholar 

  79. Muller, C., Bruhlmeier, M., Schubiger, P. A., & Schibli, R. (2006). Effects of antifolate drugs on the cellular uptake of radiofolates in vitro and in vivo. Journal of Nuclear Medicine, 47, 2057–2064.

    PubMed  CAS  Google Scholar 

  80. Weber, W. A. (2006). Positron emission tomography as an imaging biomarker. Journal of Clinical Oncology, 24, 3282–3292.

    Article  PubMed  CAS  Google Scholar 

  81. Barentsz, J., Takahashi, S., Oyen, W., Mus, R., De Mulder, P., Reznek, R., et al. (2006). Commonly used imaging techniques for diagnosis and staging. Journal of Clinical Oncology, 24, 3234–3244.

    Article  PubMed  CAS  Google Scholar 

  82. Rosenbaum, S. J., Lind, T., Antoch, G., & Bockisch, A. (2006). False-positive FDG PET uptake—the role of PET/CT. European Radiology, 16, 1054–1065.

    Article  PubMed  Google Scholar 

  83. Mathias, C. J., Lewis, M. R., Reichert, D. E., Laforest, R., Sharp, T. L., Lewis, J. S., et al. (2003). Preparation of 66Ga- and 68Ga-labeled Ga(III)-deferoxamine-folate as potential folate-receptor-targeted PET radiopharmaceuticals. Nuclear Medicine and Biology, 30, 725–731.

    Article  PubMed  CAS  Google Scholar 

  84. Schnall, M., & Rosen, M. (2006). Primer on imaging technologies for cancer. Journal of Clinical Oncology, 24, 3225–3233.

    Article  PubMed  CAS  Google Scholar 

  85. Strijkers, G. J., Mulder, W. J., van Tilborg, G. A., & Nicolay, K. (2007). MRI contrast agents: current status and future perspectives. Anti-Cancer Agents in Medicinal Chemistry, 7, 291–305.

    Article  PubMed  CAS  Google Scholar 

  86. Wiener, E. C., Konda, S. D., Wang, S., & Brechbiel, M. (2002). Imaging folate binding protein expression with MRI. Academic Radiology, 9(Suppl 2), S316–S319.

    Article  PubMed  Google Scholar 

  87. Choi, H., Choi, S. R., Zhou, R., Kung, H. F., & Chen, I. W. (2004). Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery. Academic Radiology, 11, 996–1004.

    Article  PubMed  Google Scholar 

  88. Sun, C., Sze, R., & Zhang, M. (2006). Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. Journal of Biomedical Materials Research, 78, 550–557.

    PubMed  Google Scholar 

  89. Becker, A., Hessenius, C., Licha, K., Ebert, B., Sukowski, U., Semmler, W., et al. (2001). Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nature Biotechnology, 19, 327–331.

    Article  PubMed  CAS  Google Scholar 

  90. Cai, W., Shin, D. W., Chen, K., Gheysens, O., Cao, Q., Wang, S. X., et al. (2006). Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Letters, 6, 669–676.

    Article  PubMed  CAS  Google Scholar 

  91. Michalet, X., Pinaud, F. F., Bentolila, L. A., Tsay, J. M., Doose, S., Li, J. J., et al. (2005). Quantum dots for live cells, in vivo imaging, and diagnostics. Science, 307, 538–544.

    Article  PubMed  CAS  Google Scholar 

  92. Gibson, A. P., Hebden, J. C., & Arridge, S. R. (2005). Recent advances in diffuse optical imaging. Physics in Medicine & Biology, 50, R1–R43.

    Article  CAS  Google Scholar 

  93. Kennedy, M. D., Jallad, K. N., Thompson, D. H., Ben-Amotz, D., & Low, P. S. (2003). Optical imaging of metastatic tumors using a folate-targeted fluorescent probe. Journal of Biomedical Optics, 8, 636–641.

    Article  PubMed  Google Scholar 

  94. Milstein, A. B., Kennedy, M. D., Low, P. S., Bouman, C. A., & Webb, K. J. (2005). Statistical approach for detection and localization of a fluorescing mouse tumor in intralipid. Applied Optics, 44, 2300–2310.

    Article  PubMed  CAS  Google Scholar 

  95. Tung, C. H., Lin, Y., Moon, W. K., & Weissleder, R. (2002). A receptor-targeted near-infrared fluorescence probe for in vivo tumor imaging. ChemBioChem, 3, 784–786.

    Article  PubMed  CAS  Google Scholar 

  96. Moon, W. K., Lin, Y., O’Loughlin, T., Tang, Y., Kim, D. E., Weissleder, R., et al. (2003). Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate. Bioconjugate Chemistry, 14, 539–545.

    Article  PubMed  CAS  Google Scholar 

  97. He, W., Wang, H., Hartmann, L. C., Cheng, J. X., & Low, P. S. (2007). In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry. Proceedings of the National Academy of Sciences of the United States of America, 104, 11760–11765.

    Article  PubMed  CAS  Google Scholar 

  98. Bharali, D. J., Lucey, D. W., Jayakumar, H., Pudavar, H. E., & Prasad, P. N. (2005). Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. Journal of the American Chemical Society, 127, 11364–11371.

    Article  PubMed  CAS  Google Scholar 

  99. Varghese, B., Haase, N., & Low, P. S. (2007). Depletion of folate-receptor-positive macrophages leads to alleviation of symptoms and prolonged survival in two murine models of systemic lupus erythematosus. Molecular Pharmaceutics, 4, 679–685.

    Article  PubMed  CAS  Google Scholar 

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  1. Emanuela I. Sega

    Present address: Department of Medicine, Division of Bone Marrow Transplantation, Stanford University, 269 Campus Drive, Stanford, CA, 94305, USA

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  1. Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA

    Emanuela I. Sega & Philip S. Low

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  1. Emanuela I. Sega
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  2. Philip S. Low
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Correspondence to Philip S. Low.

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Sega, E.I., Low, P.S. Tumor detection using folate receptor-targeted imaging agents. Cancer Metastasis Rev 27, 655–664 (2008). https://doi.org/10.1007/s10555-008-9155-6

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  • DOI: https://doi.org/10.1007/s10555-008-9155-6

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