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Radiolabelled RGD peptides for imaging and therapy

Abstract

Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin αvβ3. For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of αvβ3 expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy.

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References

  1. 1.

    Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1(1):27–31.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182–6.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Folkman J. Angiogenesis. Annu Rev Med 2006;57:1–18.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Folkman J, Kalluri R. Cancer without disease. Nature 2004;427:787.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Mas-Moruno C, Rechenmacher F, Kessler H. Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation. Anticancer Agents Med Chem 2010;10(10):753–68.

    Google Scholar 

  6. 6.

    Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004;3(5):391-400.

    Google Scholar 

  7. 7.

    Galbraith SM. Antivascular cancer treatments: imaging biomarkers in pharmaceutical drug development. Br J Radiol 2003;76(1):S83–6.

    PubMed  Article  Google Scholar 

  8. 8.

    Marcus CD, Ladam-Marcus V, Cucu C, Bouché O, Lucas L, Hoeffel C. Imaging techniques to evaluate the response to treatment in oncology: current standards and perspectives. Crit Rev Oncol Hematol 2009;72(3):217–38.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Jeswani T, Padhani AR. Imaging tumour angiogenesis. Cancer Imaging 2005;5:131–8.

    PubMed  Article  Google Scholar 

  10. 10.

    Takada Y, Ye X, Simon S. The integrins. Genome Biol 2007;8(5):215.

    PubMed  Article  Google Scholar 

  11. 11.

    Hynes RO, Bader BL, Hodivala-Dilke K. Integrins in vascular development. Braz J Med Biol Res 1999;32(5):501–10.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 2010;10(1):9–22.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Cai W, Chen X. Multimodality molecular imaging of tumor angiogenesis. J Nucl Med 2008;49(2):113S–28S.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Matsumoto K, Kitamura K, Mizuta T, Tanaka K, Yamamoto S, Sakamoto S, et al. Performance characteristics of a new 3-dimensional continuous-emission and spiral-transmission high-sensitivity and high-resolution PET camera evaluated with the NEMA NU 2-2001 standard. J Nucl Med 2006;47(1):83–90.

    PubMed  Google Scholar 

  15. 15.

    Chatziioannou AF. Instrumentation for molecular imaging in preclinical research: Micro-PET and Micro-SPECT. Proc Am Thorac Soc 2005;2(6):533–6, 510–11.

    PubMed  Article  Google Scholar 

  16. 16.

    Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science 1987;238(4826):491–7.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Aumailley M, Gurrath M, Müller G, Calvete J, Timpl R, Kessler H. Arg-Gly-Asp constrained within cyclic pentapeptides. Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1. FEBS Lett 1991;291(1):50–4.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Haubner R, Finsinger D, Kessler H. Stereoisomeric peptide libraries and peptidomimetics for designing selective inhibitors of the αvβ3 integrin for a new cancer therapy. Angew Chem Int Ed Engl 1997;36:1374–89.

    Article  CAS  Google Scholar 

  19. 19.

    Haubner R, Wester HJ, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman SL, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med 2001;42(2):326–36.

    PubMed  CAS  Google Scholar 

  20. 20.

    Haubner R, Wester HJ, Weber WA, Mang C, Ziegler SI, Goodman SL, et al. Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 2001;61(5):1781–5.

    PubMed  CAS  Google Scholar 

  21. 21.

    Haubner R, Kuhnast B, Mang C, Weber WA, Kessler H, Wester HJ, et al. [18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation dose estimates. Bioconjug Chem 2004;15(1):61–9.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Haubner R, Weber WA, Beer AJ, Vabuliene E, Reim D, Sarbia M, et al. Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS Med 2005;2(3):e70.

    PubMed  Article  Google Scholar 

  23. 23.

    Myoken Y, Kayada Y, Okamoto T, Kan M, Sato GH, Sato JD. Vascular endothelial cell growth factor (VEGF) produced by A-431 human epidermoid carcinoma cells and identification of VEGF membrane binding sites. Proc Natl Acad Sci U S A 1991;88(13):5819–23.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 2006;12(13):3942–9.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Beer AJ, Haubner R, Goebel M, Luderschmidt S, Spilker ME, Wester HJ, et al. Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients. J Nucl Med 2005;46(8):1333–41.

    PubMed  CAS  Google Scholar 

  26. 26.

    Beer AJ, Grosu AL, Carlsen J, Kolk A, Sarbia M, Stangier I, et al. [18F]galacto-RGD positron emission tomography for imaging of alphavbeta3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res 2007;13(22 Pt 1):6610–6.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Beer AJ, Niemeyer M, Carlsen J, Sarbia M, Nährig J, Watzlowik P, et al. Patterns of alphavbeta3 expression in primary and metastatic human breast cancer as shown by 18F-Galacto-RGD PET. J Nucl Med 2008;49(2):255–9.

    PubMed  Article  Google Scholar 

  28. 28.

    Schnell O, Krebs B, Wagner E, Romagna A, Beer AJ, Grau SJ, et al. Expression of integrin alphavbeta3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature. Brain Pathol 2008;18(3):378–86.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Pichler BJ, Kneilling M, Haubner R, Braumüller H, Schwaiger M, Röcken M, et al. Imaging of delayed-type hypersensitivity reaction by PET and 18F-galacto-RGD. J Nucl Med 2005;46(1):184–9.

    PubMed  Google Scholar 

  30. 30.

    Beer AJ, Schwaiger M. Molecular imaging with new PET tracers. Radiologe 2007;47(1):8–17.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Beer AJ, Haubner R, Wolf I, Goebel M, Luderschmidt S, Niemeyer M, et al. PET-based human dosimetry of 18F-galacto-RGD, a new radiotracer for imaging alpha v beta3 expression. J Nucl Med 2006;47(5):763–9.

    PubMed  CAS  Google Scholar 

  32. 32.

    ICRP. Radiation dose to patients from radiopharmaceuticals. Addendum 3 to ICRP Publication 53. ICRP Publication 106. Approved by the Commission in October 2007. Ann ICRP 2008;38(1-2):1–197.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Huang B, Law MW, Khong PL. Whole-body PET/CT scanning: estimation of radiation dose and cancer risk. Radiology 2009;251(1):166–74.

    PubMed  Article  Google Scholar 

  34. 34.

    Kenny LM, Coombes RC, Oulie I, Contractor KB, Miller M, Spinks TJ, et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med 2008;49(6):879–86.

    PubMed  Article  Google Scholar 

  35. 35.

    McParland BJ, Miller MP, Spinks TJ, Kenny LM, Osman S, Khela MK, et al. The biodistribution and radiation dosimetry of the Arg-Gly-Asp peptide 18F-AH111585 in healthy volunteers. J Nucl Med 2008;49(10):1664–7.

    PubMed  Article  Google Scholar 

  36. 36.

    Winick J. A proof-of-concept study to assess the ability of [18F]AH-111585 PET imaging to detect tumours and angiogenesis. 2011(11/10/2011), ClinicalTrials.gov 2007.

  37. 37.

    Kolb H, Walsh J, Liang Q, Zhao T, Gao D, Secrest J, et al. 18F-RGD-K5: a cyclic triazole-bearing RGD peptide for imaging integrin αvβ3 expression in vivo. J Nucl Med 2009;50(2):329.

    Article  Google Scholar 

  38. 38.

    Cho HJ, Lee DL, Park JY, Yun M, Kang WJ, Walsh JC, et al. First in human evaluation of a newly developed PET tracer, 18F-RGD-K5 in patients with breast cancer: comparison with 18F-FDG uptake pattern and microvessel density. J Nucl Med 2009;50(2):1910.

    CAS  Google Scholar 

  39. 39.

    Doss M, Alpaugh RK, Yu JQ. Biodistribution and radiation dosimetry of angiogenesis marker [18F]RGD-K5 measured using human PET. J Nucl Med 2009;50(2):447.

    Google Scholar 

  40. 40.

    Chen X, Park R, Tohme M, Shahinian AH, Bading JR, Conti PS. MicroPET and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD peptide. Bioconjug Chem 2004;15(1):41–9.

    PubMed  Article  Google Scholar 

  41. 41.

    Chen X, Hou Y, Tohme M, Park R, Khankaldyyan V, Gonzales-Gomez I, et al. Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor alphavbeta3-integrin expression. J Nucl Med 2004;45(10):1776–83.

    PubMed  CAS  Google Scholar 

  42. 42.

    Breeman WA, Verbruggen AM. The 68Ge/68Ga generator has high potential, but when can we use 68Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging 2007;34(7):978–81.

    PubMed  Article  Google Scholar 

  43. 43.

    Jeong JM, Hong MK, Chang YS, Lee YS, Kim YJ, Cheon GJ, et al. Preparation of a promising angiogenesis PET imaging agent: 68Ga-labeled c(RGDyK)-isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid and feasibility studies in mice. J Nucl Med 2008;49(5):830–6.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Knetsch PA, Petrik M, Griessinger CM, Rangger C, Fani M, Kesenheimer C, et al. [68Ga]NODAGA-RGD for imaging alphavbeta3 integrin expression. Eur J Nucl Med Mol Imaging 2011;38(7):1303–12.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Fanti S, Farsad M, Mansi L. PET-CT beyond FDG: a quick guide to image interpretation. 1st ed. Berlin: Springer; 2010.

    Book  Google Scholar 

  46. 46.

    Poethko T, Schottelius M, Thumshirn G, Herz M, Haubner R, Henriksen G, et al. Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation. Radiochim Acta 2004;92(4–6):317–27.

    Article  CAS  Google Scholar 

  47. 47.

    Chen X, Liu S, Hou Y, Tohme M, Park R, Bading JR, et al. MicroPET imaging of breast cancer alphav-integrin expression with 64Cu-labeled dimeric RGD peptides. Mol Imaging Biol 2004;6(5):350–9.

    PubMed  Article  Google Scholar 

  48. 48.

    Wu Y, Zhang X, Xiong Z, Cheng Z, Fisher DR, Liu S, et al. microPET imaging of glioma integrin {alpha}v{beta}3 expression using (64)Cu-labeled tetrameric RGD peptide. J Nucl Med 2005;46(10):1707–18.

    PubMed  CAS  Google Scholar 

  49. 49.

    Li ZB, Cai W, Cao Q, Chen K, Wu Z, He L, et al. (64)Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor alpha(v)beta(3) integrin expression. J Nucl Med 2007;48(7):1162–71.

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    Shi J, Kim YS, Zhai S, Liu Z, Chen X, Liu S. Improving tumor uptake and pharmacokinetics of (64)Cu-labeled cyclic RGD peptide dimers with Gly(3) and PEG(4) linkers. Bioconjug Chem 2009;20(4):750–9.

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Liu Z, Niu G, Shi J, Liu S, Wang F, Chen X. (68)Ga-labeled cyclic RGD dimers with Gly3 and PEG4 linkers: promising agents for tumor integrin alphavbeta3 PET imaging. Eur J Nucl Med Mol Imaging 2009;36(6):947–57.

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Notni J, Simecek J, Hermann P, Wester HJ. TRAP, a powerful and versatile framework for Gallium-68 radiopharmaceuticals. Chemistry 2011;17(52):14718–22.

    Google Scholar 

  53. 53.

    Wu Z, Li ZB, Cai W, He L, Chin FT, Li F, et al. 18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of alphavbeta3 integrin expression. Eur J Nucl Med Mol Imaging 2007;34(11):1823–31.

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Chen X, Tohme M, Park R, Hou Y, Bading JR, Conti PS. Micro-PET imaging of alphavbeta3-integrin expression with 18F-labeled dimeric RGD peptide. Mol Imaging 2004;3(2):96–104.

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Zhang X, Xiong Z, Wu Y, Cai W, Tseng JR, Gambhir SS, et al. Quantitative PET imaging of tumor integrin alphavbeta3 expression with 18F-FRGD2. J Nucl Med 2006;47(1):113–21.

    PubMed  CAS  Google Scholar 

  56. 56.

    Liu Z, Liu S, Wang F, Liu S, Chen X. Noninvasive imaging of tumor integrin expression using (18)F-labeled RGD dimer peptide with PEG (4) linkers. Eur J Nucl Med Mol Imaging 2009;36(8):1296–307.

    PubMed  Article  CAS  Google Scholar 

  57. 57.

    Wu Z, Li ZB, Chen K, Cai W, He L, Chin FT, et al. microPET of tumor integrin alphavbeta3 expression using 18F-labeled PEGylated tetrameric RGD peptide (18F-FPRGD4). J Nucl Med 2007;48(9):1536–44.

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Liu S, Liu Z, Chen K, Yan Y, Watzlowik P, Wester HJ, et al. (18)F-labeled galacto and PEGylated RGD dimers for PET imaging of ανβ3 integrin expression. Mol Imaging Biol 2010;12(5)530–8.

    PubMed  Article  Google Scholar 

  59. 59.

    Mittra ES, Goris ML, Iagaru AH, Kardan A, Burton L, Berganos R, et al. Pilot pharmacokinetic and dosimetric studies of (18)F-FPPRGD2: a PET radiopharmaceutical agent for imaging alpha(v)beta(3) integrin levels. Radiology 2011;260(1):182–91.

    PubMed  Article  Google Scholar 

  60. 60.

    Sivolapenko GB, Skarlos D, Pectasides D, Stathopoulou E, Milonakis A, Sirmalis G, et al. Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide. Eur J Nucl Med 1998;25(10):1383–9.

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Hua J, Dobrucki LW, Sadeghi MM, Zhang J, Bourke BN, Cavaliere P, et al. Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at alphavbeta3 integrin after murine hindlimb ischemia. Circulation 2005;111(24):3255–60.

    PubMed  Article  CAS  Google Scholar 

  62. 62.

    Bach-Gansmo T, Danielsson R, Saracco A, Wilczek B, Bogsrud TV, Fangberget A, et al. Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692. J Nucl Med 2006;47(9):1434–9.

    PubMed  CAS  Google Scholar 

  63. 63.

    Axelsson R, Bach-Gansmo T, Castell-Conesa J, McParland BJ. An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the alpha v beta 3-selective angiogenesis imaging agent 99mTc-NC100692. Acta Radiol 2010;51(1):40–6.

    PubMed  Article  Google Scholar 

  64. 64.

    Contois L, Akalu A, Brooks PC. Integrins as “functional hubs” in the regulation of pathological angiogenesis. Semin Cancer Biol 2009;19:318–28.

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Rathinam R, Alahari SK. Important role of integrins in the cancer biology. Cancer Metastasis Rev 2010;29:223–37.

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    McGary EC, Lev DC, Bar-Eli M. Cellular adhesion pathways and metastatic potential of human melanoma. Cancer Biol Ther 2002;1(5):459–65.

    PubMed  Google Scholar 

  67. 67.

    Johnson JP. Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev 1999;18(3):345–57.

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Rolli M, Fransvea E, Pilch J, Saven A, Felding-Habermann B. Activated integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells. Proc Natl Acad Sci U S A 2003;100(16):9482–7.

    PubMed  Article  CAS  Google Scholar 

  69. 69.

    Liapis H, Flath A, Kitazawa S. Integrin alpha V beta 3 expression by bone-residing breast cancer metastases. Diagn Mol Pathol 1996;5(2):127–35.

    PubMed  Article  CAS  Google Scholar 

  70. 70.

    Brooks PC, Stromblad S, Klemke R, Visscher D, Sarkar FH, Cheresh DA. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. J Clin Invest 1995;96(4):1815–22.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Burke PA, DeNardo SJ, Miers LA, Lamborn KR, Matzku S, DeNardo GL. Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer Res 2002;62(15):4263–72.

    PubMed  CAS  Google Scholar 

  72. 72.

    Nabors LB, Mikkelsen T, Rosenfeld SS, Hochberg F, Akella NS, Fisher JD, et al. Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 2007;25(13):1651–7.

    PubMed  Article  CAS  Google Scholar 

  73. 73.

    Reardon DA, Nabors LB, Stupp R, Mikkelsen T. Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme. Expert Opin Investig Drugs 2008;17(8):1225–35.

    PubMed  Article  CAS  Google Scholar 

  74. 74.

    Zhang ZJ, Chen JH, Meng L, Du JJ, Zhang L, Liu Y, et al. 18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer. Chin Med J (Engl) 2007;120(2):125–31.

    Google Scholar 

  75. 75.

    Higashi K, Ito K, Hiramatsu Y, Ishikawa T, Sakuma T, Matsunari I, et al. 18F-FDG uptake by primary tumor as a predictor of intratumoral lymphatic vessel invasion and lymph node involvement in non-small cell lung cancer: analysis of a multicenter study. J Nucl Med 2005;46(2):267–73.

    PubMed  Google Scholar 

  76. 76.

    Lee JD, Yun M, Lee JM, Choi Y, Kim JS, Kim SJ, et al. Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography. Eur J Nucl Med Mol Imaging 2004;31(12):1621–30.

    PubMed  Article  CAS  Google Scholar 

  77. 77.

    Beer AJ, Lorenzen S, Metz S, Herrmann K, Watzlowik P, Wester HJ, et al. Comparison of integrin alphaVbeta3 expression and glucose metabolism in primary and metastatic lesions in cancer patients: a PET study using 18F-galacto-RGD and 18F-FDG. J Nucl Med 2008;49(1):22–9.

    PubMed  Article  Google Scholar 

  78. 78.

    Sloan EK, Pouliot N, Stanley KL, Chia J, Moseley JM, Hards DK, et al. Tumor-specific expression of alphavbeta3 integrin promotes spontaneous metastasis of breast cancer to bone. Breast Cancer Res 2006;8(2):R20.

    PubMed  Article  Google Scholar 

  79. 79.

    Nakamura I, Pilkington MF, Lakkakorpi PT, Lipfert L, Sims SM, Dixon SJ, et al. Role of alpha(v)beta(3) integrin in osteoclast migration and formation of the sealing zone. J Cell Sci 1999;112(Pt 22):3985–93.

    PubMed  CAS  Google Scholar 

  80. 80.

    Morrison MS, Ricketts SA, Barnett J, Cuthbertson A, Tessier J, Wedge SR. Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy. J Nucl Med 2009;50(1):116–22.

    PubMed  Article  CAS  Google Scholar 

  81. 81.

    Battle MR, Goggi JL, Allen L, Barnett J, Morrison MS. Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled alphaVbeta3-integrin and alphaV beta5-integrin imaging agent. J Nucl Med 2011;52(3):424–30.

    PubMed  Article  CAS  Google Scholar 

  82. 82.

    Dumont RA, Hildebrandt I, Su H, Haubner R, Reischi G, Czernin JG, et al. Noninvasive imaging of alphaVbeta3 function as a predictor of the antimigratory and antiproliferative effects of dasatinib. Cancer Res 2009;69(7):3173–9.

    PubMed  Article  CAS  Google Scholar 

  83. 83.

    Kurdziel KA. A pilot, open-label study of 18F-fluciclatide PET/CT imaging in the evaluation of anti-angiogenic therapy in solid tumors. ClinicalTrials.gov. 2010.

  84. 84.

    Kolb H. Efficacy study of [F-18]RGD-K5 positron emission tomography (PET) as a tool to monitor response to an anti-angiogenic drug (K5-101). ClinicalTrials.gov. 2010.

  85. 85.

    van Essen M, Krenning EP, Kam BL, de Jong M, Valkema R, Kwekkeboom DJ. Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol 2009;5(7):382–93.

    PubMed  Article  Google Scholar 

  86. 86.

    Janssen ML, Oyen WJ, Dijkgraaf I, Massuger LF, Frielink C, Edwards DS, et al. Tumor targeting with radiolabeled alpha(v)beta(3) integrin binding peptides in a nude mouse model. Cancer Res 2002;62(21):6146–51.

    PubMed  CAS  Google Scholar 

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Gaertner, F.C., Kessler, H., Wester, HJ. et al. Radiolabelled RGD peptides for imaging and therapy. Eur J Nucl Med Mol Imaging 39, 126–138 (2012). https://doi.org/10.1007/s00259-011-2028-1

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Keywords

  • Angiogenesis
  • RGD peptides
  • Molecular imaging