Peptide Receptor Radionuclide Therapy (PRRT)

  • F. F. (Russ) Knapp
  • Ashutosh Dash


There has been tremendous progress over recent years on the development of peptide receptor radionuclide therapy (PRRT) for the treatment of a variety of cancers. In this technology, peptides radiolabeled with therapeutic radionuclides are targeted to cell-surface receptors which are often overexpressed on the membrane surface of tumor cells. This targeting strategy localizes particle-emitting radioisotopes to tumors. The use of peptides radiolabeled with particle-emitting radionuclides is a relatively new and promising treatment modality which can provide effective and innovative solutions for unmet therapeutic needs. We describe in this chapter the concepts involved in targeting peptides to tumor-associated cell-surface receptors and the preparation of targeted peptides to which chemical-binding groups have been attached to bind a variety of therapeutic radionuclides for targeted therapeutic applications.


Vasoactive Intestinal Peptide Peptide Receptor Radionuclide Therapy Peptide Analog Vasoactive Intestinal Peptide Receptor Therapeutic Radionuclide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Anthony LB, Woltering EA, Espanan GD, et al. Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med. 2002;32:123–32.PubMedCrossRefGoogle Scholar
  2. Antonov AS, Kolodgie FD, Munn DH, et al. Regulation of macrophage foam cell formation by αvβ3 integrin: potential role in human atherosclerosis. Am J Pathol. 2004;165:247–58.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer. 2008;8:604–17.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bakker WH, Breeman WAP, van der Pluijm ME, et al. Iodine-131 labeled octreotide: not an option for somatostatin receptor therapy. Eur J Nucl Med. 1996;23:775.PubMedCrossRefGoogle Scholar
  5. Behr TM, Behe MP. Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies. Semin Nucl Med. 2002;32:97–109.PubMedCrossRefGoogle Scholar
  6. Bennett JS, Berger BW, Billings PC. The structure and function of platelet integrins. J Thromb Haemost. 2009;7 Suppl 1:200–5.PubMedCrossRefGoogle Scholar
  7. Bernard BF, Béhé M, Breeman WAP, et al. Preclinical evaluation of minigastrin analogs for CCK-B receptor targeting. Cancer Biother Radiopharm. 2003;18:28.Google Scholar
  8. Bodei L, Cremonesi M, Grana C, et al. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2004;31:1038–46.PubMedCrossRefGoogle Scholar
  9. Brans B, Linden O, Giammarile F, Tennvall J, Punt C. Clinical applications of newer radionuclide therapies. Eur J Cancer. 2006;42:994–1003.Google Scholar
  10. Bunnett G. Gastrin-releasing peptide. In: Walsh JH, Dockray GJ, editors. Gut peptides: biochemistry and physiology. New York: Raven Press, Ltd; 1994. p. 423–45.Google Scholar
  11. Burke PA, DeNardo SJ. Antiangiogenic agents and their promising potential in combined therapy. Crit Rev Oncol Hematol. 2001;39:155–71.PubMedCrossRefGoogle Scholar
  12. Bushnell Jr DL, O’Dorisio TM, O’Dorisio MS, et al. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010;28:1652–9.PubMedCrossRefGoogle Scholar
  13. Cai W, Niu G, Chen X. Imaging of integrins as biomarkers for tumor angiogenesis. Curr Pharm Des. 2008;14:2943–73.PubMedCrossRefGoogle Scholar
  14. Carmeliet P, Collen D. Transgenic mouse models in angiogenesis and cardiovascular disease. J Pathol. 2000;190(3):387–405.PubMedCrossRefGoogle Scholar
  15. Caswell PT, Vadrevu S, Norman JC. Integrins: masters and slaves of endocytic transport. Nat Rev Mol Cell Biol. 2009;10:843–53.PubMedCrossRefGoogle Scholar
  16. Chao JT, Meininger GA, Patterson JL, et al. Regulation of α7-integrin expression in vascular smooth muscle by injury-induced atherosclerosis. Am J Physiol Heart Circ Physiol. 2004;287:H381–9.PubMedCrossRefGoogle Scholar
  17. Chen X. Multimodality imaging of tumor integrin αvβ3 expression. Mini Rev Med Chem. 2006;6:227–34.PubMedCrossRefGoogle Scholar
  18. Chen JQ, Giblin MF, Wang N, et al. In vivo evaluation of 99mTc/188Re-labeled linear alpha-melanocyte stimulating hormone analogs for specific melanoma targeting. Nucl Med Biol. 1999;26:687–93.PubMedCrossRefGoogle Scholar
  19. Cheng Z, Zhang L, Graves E, et al. Small-animal PET of melanocortin 1 receptor expression using a 18F-labeled α-melanocyte-stimulating hormone analog. J Nucl Med. 2007;48:987–94.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chinol M, Bodei L, Cremonesi M, Paganelli G. Receptor-mediated radiotherapy with Y-DOTA-DPhe-Tyroctreotide: the experience of the European Institute of Oncology Group. Semin Nucl Med. 2002;32:141–7.PubMedCrossRefGoogle Scholar
  21. Christ E, Wild D, Forrer F, et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J Clin Endocrinol Metab. 2009;94:4398–405.PubMedCrossRefGoogle Scholar
  22. Chung J, Yoon SO, Lipscomb EA, Mercurio AM. The Met receptor and α6β4 integrin can function independently to promote carcinoma invasion. J Biol Chem. 2004;279:32287–93.PubMedCrossRefGoogle Scholar
  23. Cordier D, Forrer F, Bruchertseifer F, et al. Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8, Met(O2)11]-substance P: a pilot trial. Eur J Nucl Med Mol Imaging. 2010;37:1335–44.PubMedCrossRefGoogle Scholar
  24. de Herder WW, Hofland LJ, van der Lely AJ, Lamberts SW. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer. 2003;10:451–8.PubMedCrossRefGoogle Scholar
  25. de Jong M, Breeman WA, Bernard BF, et al. Tumour uptake of the radiolabelled somatostatin analogue [DOTA0, TYR3]octreotide is dependent on the peptide amount. Eur J Nucl Med. 1999;26:693–8.PubMedCrossRefGoogle Scholar
  26. de Visser M, van Weerden WM, de Ridder CM, et al. Androgen-dependent expression of the gastrin-releasing peptide receptor in human prostate tumor xenografts. J Nucl Med. 2007;48:88–93.PubMedGoogle Scholar
  27. Dijkgraaf I, Kruijtzer JA, Liu S, et al. Improved targeting of the αvβ3 integrin by multi-merisation of RGD peptides. Eur J Nucl Med Mol Imaging. 2007;34:267–73.PubMedCrossRefGoogle Scholar
  28. Drucker DJ. Minireview the glucagon-like peptides. Endocrinology. 2001;142:521–7.PubMedCrossRefGoogle Scholar
  29. Eble JA, Haier J. Integrins in cancer treatment. Curr Cancer Drug Targets. 2006;6:89–105.PubMedCrossRefGoogle Scholar
  30. ENETS Consensus Guidelines. In: de Herder WW, O’Toole D, Rindi G, Wiedenmann B, editors. ENETS consensus guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumors Part 2 – Midgut and Hindgut Tumors. Neuroendocrinology Special Issue, vol. 87. Basel: Karger Medical and Scientific Publishers; 2008, No. 1. ISBN: 978-3-8055-8459-3; e-ISBN: 978-3-8055-8460-9; DOI:  10.1159/isbn.978-3-8055-8460.
  31. Francavilla C, Maddaluno L, Cavallaro U. The functional role of cell adhesion molecules in tumor angiogenesis. Semin Cancer Biol. 2009;19:298–309.PubMedCrossRefGoogle Scholar
  32. Froberg AC, de Jong M, Nock BA, et al. Comparison of three radiolabelled peptide analogues for CCK-2 receptor scintigraphy in medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2009;36:1265–72.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Furger KA, Allan AL, Wilson SM, et al. Beta(3) integrin expression increases breast carcinoma cell responsiveness to the malignancy-enhancing effects of osteopontin. Mol Cancer Res. 2003;1:810–9.PubMedGoogle Scholar
  34. Gonzalez N, Moody TW, Igarashi H, et al. Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. Curr Opin Endocrinol Diabetes Obes. 2008;15:58–64.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Gottschalk KE, Kessler H. The structures of integrins and integrin-ligand complexes: Implications for drug design and signal transduction. Angew Chem Int Ed Engl. 2002;41:3767–74.PubMedCrossRefGoogle Scholar
  36. Guo W, Giancotti FG. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. 2004;5:816–26.PubMedCrossRefGoogle Scholar
  37. Hassan M, Eskilsson A, Nilsson C, et al. In vivo dynamic distribution of 131I-glucagon-like peptide-1 (7-36) amide in the rat studied by gamma camera. Nucl Med Biol. 1999;26:413.PubMedCrossRefGoogle Scholar
  38. Heppeler A, Froidevaux S, Eberle AN, Maecke HR. Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem. 2000;7:971–94.PubMedCrossRefGoogle Scholar
  39. Hessenius C, Bäder M, Meinhold H, et al. Vasoactive intestinal peptide receptor scintigraphy in patients with pancreatic adenocarcinomas or neuroendocrine tumors. Eur J Nucl Med. 2000;27:1684–93.PubMedCrossRefGoogle Scholar
  40. Hilden TJ, Nurmi SM, Fagerholm SC, Gahmberg CG. Interfering with leukocyte integrin activation-a novel concept in the development of anti-inflammatory drugs. Ann Med. 2006;38:503–11.PubMedCrossRefGoogle Scholar
  41. Hollenbeck ST, Itoh H, Louie O, et al. Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60src-dependent crosstalk between the α2β1 integrin and PDGFβ receptor. Biochem Biophys Res Commun. 2004;325:328–37.PubMedCrossRefGoogle Scholar
  42. Horton MA. Interactions of connective tissue cells with the extracellular matrix. Bone. 1995;17:51S–3.PubMedCrossRefGoogle Scholar
  43. Hosotani R, Kawaguchi M, Masui T, et al. Expression of integrin alphaVbeta3 in pancreatic carcinoma: relation to MMP-2 activation and lymph node metastasis. Pancreas. 2002;25:e30–5.PubMedCrossRefGoogle Scholar
  44. Hubalewska-Dydejczyk A, Sowa-Staszczak A, Mikolajczak R, et al. 99mTc labeled GLP-1 scintigraphy with the use of [Lys40-(Ahx-HYNIC/EDDA)NH2]-Exendin-4 in the insulinoma localization. J Nucl Med. 2011;52 Suppl 1:561.Google Scholar
  45. Igarashi H, Ito T, Mantey SA, Pradhan TK, et al. Development of simplified vasoactive intestinal peptide analogs with receptor selectivity and stability for human vasoactive intestinal pep-tide/pituitary adenylate cyclase-activating polypeptide receptors. J Pharmacol Exp Ther. 2005;315:370–81.PubMedCrossRefGoogle Scholar
  46. Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity after therapy with the radio-labeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23.PubMedCrossRefGoogle Scholar
  47. Isberg RR, Van Nhieu GT. The mechanism of phagocytic uptake promoted by invasin-integrin interaction. Trends Cell Biol. 1995;5:120–4.PubMedCrossRefGoogle Scholar
  48. Iten F, Muller B, Schindler C, et al. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin Cancer Res. 2007;13:6696–702.PubMedCrossRefGoogle Scholar
  49. Jain R. Transport of molecules in the tumor interstitium: a review. Cancer Res. 1987;47:3039–51.PubMedGoogle Scholar
  50. Jong M, Valkema R, Jamar F, et al. Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Semin Nucl Med. 2002;32(2):133–40.PubMedCrossRefGoogle Scholar
  51. Kaltsas GA, Papadogias D, Makras P, Grossman AB. Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues. Endocr Relat Cancer. 2005;2:683–99.CrossRefGoogle Scholar
  52. Korner M, Stockli M, Waser B, et al. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007;48:736.PubMedCrossRefGoogle Scholar
  53. Krenning EP, de Jong M, Kooij PP, et al. Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol. 1999;10 Suppl 2:S23–9.PubMedCrossRefGoogle Scholar
  54. Krenning EP, Valkema R, Kwekkeboom DJ, et al. Molecular imaging as in vivo molecular pathology for gastroenteropancreatic neuroendocrine tumors: implications for follow-up after therapy. J Nucl Med. 2005;46 Suppl 1:76S–82.PubMedGoogle Scholar
  55. Kunikowska J, Krolicki L, Hubalewska-Dydejczyk A. Clinical results of radionuclide therapy of neuroendocrine tumours with (90)Y-DOTATATE and tandem (90)Y/(177)Lu-DOTATATE: which is a better therapy option? Eur J Nucl Med Mol Imaging. 2011;38(10):1788–97.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kwekkeboom DJ, Teunissen JJ, Bakker WH, et al. Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate in patients with endocrine gastroentero-pancreatic tumors. J Clin Oncol. 2005;23:2754–62.PubMedCrossRefGoogle Scholar
  57. Kwekkeboom DJ, Teunissen JJ, Kam BL, Valkema R, de Herder WW, Krenning EP. Treatment of patients who have endocrine gastroenteropancreatic tumors with radiolabeled somatostatin analogues. Hematol Oncol Clin North Am. 2007;21:561–73.Google Scholar
  58. Lal H, Verma SK, Foster DM, et al. Integrins and proximal signaling mechanisms in cardiovascular disease. Front Biosci. 2009;14:2307–34.CrossRefGoogle Scholar
  59. Laverman P, Joosten L, Eek A, et al. Comparative biodistribution of 12 111In-labelled gastrin/CCK2 receptor-targeting peptides. Eur J Nucl Med Mol Imaging. 2011;38:1410–6.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Liu S. Radiolabeled multimeric cyclic RGD peptides as integrin αvβ3 targeted radiotracers for tumor imaging. Mol Pharm. 2006;3:472–87.PubMedCrossRefGoogle Scholar
  61. Liu S. Radiolabeled cyclic RGD peptides as integrin αvβ3-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug Chem. 2009;20:2199–213.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Liu Z, Liu S, Wang F, Liu S, Chen X. Noninvasive imaging of tumor integrin expression using 18F-labeled RGD dimer peptide with PEG4 linkers. Eur J Nucl Med Mol Imaging. 2009;36:1296–307.PubMedCrossRefGoogle Scholar
  63. Liu Z, Liu S, Niu G, Wang F, Liu S, Chen X. Optical imaging of integrin αvβ3 expression with near-infrared fluorescent RGD dimer with tetra(ethylene glycol) linkers. Mol Imaging. 2010;9:21–9.PubMedPubMedCentralGoogle Scholar
  64. MacDonald PE, El-Kholy W, Riedel MJ, et al. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes. 2002;51 Suppl 3:S434–42.PubMedCrossRefGoogle Scholar
  65. Maddalena ME, Fox J, Chen J, et al. 177Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. J Nucl Med. 2009;50:2017–24.PubMedCrossRefGoogle Scholar
  66. Mariani G, Erba PA, Signore A. Receptor-mediated tumor targeting with radiolabeled peptides: there is more to it than somatostatin analogs. J Nucl Med. 2006;47:1904–7.PubMedGoogle Scholar
  67. Meier JJ, Nauck MA. Glucagon-like peptide 1 (GLP-1) in biology and pathology. Diabetes Metab Res Rev. 2005;21:91.PubMedCrossRefGoogle Scholar
  68. Miao Y, Benwell K, Quinn TP. 99mTc- and 111In-labeled α-melanocyte-stimulating hormone peptides as imaging probes for primary and pulmonary metastatic melanoma detection. J Nucl Med. 2007;48:73–80.PubMedGoogle Scholar
  69. Miller WH, Keenan RM, Willette RN, et al. Identification and in vivo efficacy of small-molecule antagonists of integrin αvβ3 (the vitronectin receptor). Drug Discov Today. 2000;5:397–408.PubMedCrossRefGoogle Scholar
  70. Miyata S, Koshikawa N, Yasumitsu H, et al. Trypsin stimulates integrin α5β1-dependent adhesion to fibronectin and proliferation of human gastric carcinoma cells through activation of proteinase-activated receptor-2. J Biol Chem. 2000;275:4592–8.PubMedCrossRefGoogle Scholar
  71. Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.PubMedCrossRefGoogle Scholar
  72. Nissinen L, Pentikäinen OT, Jouppila A, et al. A small-molecule inhibitor of integrin α2β1 introduces a new strategy for antithrombotic therapy. Thromb Haemost. 2010;103:387–97.PubMedCrossRefGoogle Scholar
  73. Nock BA, Maina T, Behe M, et al. CCK-2/gastrin receptor-targeted tumor imaging with 99mTc-labeled minigastrin analogs. J Nucl Med. 2005;46:1727–3176.PubMedGoogle Scholar
  74. Norenberg JP, Krenning BJ, Konings IRHM, et al. 213Bi-[DOTA0, Tyr3]octreotide peptide receptor radionuclide therapy of pancreatic tumors in a preclinical animal model. Clin Cancer Res. 2006;12:897–903.PubMedCrossRefGoogle Scholar
  75. Oberg K. Carcinoid tumors: molecular genetics, tumor biology, and update of diagnosis and treatment. Curr Opin Oncol. 2002;14:38–45.PubMedCrossRefGoogle Scholar
  76. Oberg K. Future aspects of somatostatin-receptor mediated therapy. Neuroendocrinology. 2004;80 Suppl 1:57–61.PubMedGoogle Scholar
  77. Ohki-Hamazaki H, Iwabuchi M, Maekawa F. Development and function of bombesin-like peptides and their receptors. Int J Dev Biol. 2005;49:293–300.PubMedCrossRefGoogle Scholar
  78. Okarvi SM. Peptide-based radiopharmaceuticals: future tools for diagnostic imaging of cancers and other diseases. Med Res Rev. 2004;24:357–97.PubMedCrossRefGoogle Scholar
  79. Otte A, Mueller-Brand J, Dellas S, et al. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet. 1998;351:417.PubMedCrossRefGoogle Scholar
  80. Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, Maecke HR, Muller J. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med. 1999;26:1439–47.Google Scholar
  81. Pansky P, De Weerth A, Fasler-Kan E, et al. Gastrin releasing peptide-preferring bombesin receptors mediate growth of human renal cell carcinoma. J Am Soc Nephrol. 2000;11:1409–18.PubMedGoogle Scholar
  82. Pattou F, Kerr-Conte J, Wild D. GLP-1-receptor scanning for imaging of human beta cells transplanted in muscle. N Engl J Med. 2010;363:1289–90.PubMedCrossRefGoogle Scholar
  83. Prasanphanich AF, Nanda PK, Rold TL, et al. [64Cu-NOTA-8-Aoc-BBN(7-14)NH2] targeting vector for positron-emission tomography imaging of gastrin-releasing peptide receptor-expressing tissues. Proc Natl Acad Sci U S A. 2007;104:12462–7.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Raderer M, Kurtaran A, Leimer M, et al. Value of peptide receptor scintigraphy using 123I-vasoactive intestinal peptide and 111In-DTPA-D-Phe1-octreotide in 194 carcinoid patients: Vienna University Experience, 1993 to 1998. J Clin Oncol. 2000;18:1331–6.PubMedGoogle Scholar
  85. Reardon DA, Nabors LB, Stupp R. Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme. Expert Opin Investig Drugs. 2008;17:1225–35.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Reubi JC, Macke HR, Krenning EP. Candidates for peptide receptor radiotherapy today and in the future. J Nucl Med. 2005;46 Suppl 1:67S–75.PubMedGoogle Scholar
  87. Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med. 2006;36:228–47.Google Scholar
  88. Sheldrak HM, Patterson LH. Function and antagonism of beta3 integrins in the development of cancer therapy. Curr Cancer Drug Targets. 2009;9:519–40.CrossRefGoogle Scholar
  89. Shi J, Wang L, Kim YS, et al. Improving tumor uptake and excretion kinetics of 99mTc-labeled cyclic arginine-glycine-aspartic (RGD) dimers with triglycine linkers. J Med Chem. 2008;51:7980–90.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Shi J, Kim YS, Zhai S, et al. Improving tumor uptake and pharmacokinetics of 64Cu-labeled cyclic RGD pep-tide dimers with Gly3 and PEG4 linkers. Bioconjug Chem. 2009;20:750–9.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Singh P, Reimer CL, Peters JH, et al. The spatial and temporal expression patterns of integrin α9β1 and one of its ligands, the EIIIA segment of fibronectin, in cutaneous wound healing. J Invest Dermatol. 2004;123:1176–81.PubMedCrossRefGoogle Scholar
  92. Smith JW. Cilengitide Merck. Curr Opin Investig Drugs. 2003;4:741–5.PubMedGoogle Scholar
  93. Smith CJ, Gali H, Sieckman GL, et al. Radiochemical investigations of 177Lu-DOTA-8-Aoc-BBN[7-14]NH2: an in vitro/in vivo assessment of the targeting ability of this new radio-pharmaceutical for PC-3 human prostate cancer cells. Nucl Med Biol. 2003;30:101–9.PubMedCrossRefGoogle Scholar
  94. Sowa-Staszczak A, Stefanska A, Pach D, et al. First clinical application of 99mTc labelled long-acting agonist of GLP-1 (Exendin-4) in endocrine diagnosis. Eur J Nucl Med Mol Imaging. 2011;38 Suppl 2:S206.Google Scholar
  95. Stefanelli T, Malesci A, De La Rue SA, Danese S. Anti-adhesion molecule therapies in inflammatory bowel disease: touch and go. Autoimmun Rev. 2008;7:364–9.PubMedCrossRefGoogle Scholar
  96. Switala-Jelen K, Dabrowska K, Opolski A, et al. The biological functions of beta3 integrins. Folia Biol (Praha). 2004;50:143–52.Google Scholar
  97. Takayama S, Ishii S, Ikeda T, et al. The relationship between bone metastasis from human breast cancer and integrin alpha(v)beta3 expression. Anticancer Res. 2005;25:79–83.PubMedGoogle Scholar
  98. Tanaka K, Masu M, Nakanishi S. Structure and functional expression of the cloned rat neurotensin receptor. Neuron. 1990;4:847–54.PubMedCrossRefGoogle Scholar
  99. Tang-Christensen M, Larsen PJ, Thulesen J, et al. The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat Med. 2000;6(7):802–7.PubMedCrossRefGoogle Scholar
  100. Temming K, Schiffelers RM, Molema G, Kok RJ. RGD based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist Updat. 2005;8:381–402.PubMedCrossRefGoogle Scholar
  101. Teunissen JJ, Kwekkeboom DJ, de Jong M, et al. Endocrine tumours of the gastrointestinal tract. Peptide receptor radionuclide therapy. Best Pract Res Clin Gastroenterol. 2005;9:595–616.CrossRefGoogle Scholar
  102. Tsuji T. Physiological and pathological roles of α3β1 integrin. J Membr Biol. 2004;200:115–32.PubMedCrossRefGoogle Scholar
  103. Tucker GC. Integrins: molecular targets in cancer therapy. Curr Oncol Rep. 2006;8:96–103.PubMedCrossRefGoogle Scholar
  104. Valkema R, de Jong M, Bakker WH, et al. Phase I study of peptide receptor radionuclide therapy with [111In-DTPA0]Octreotide: The Rotterdam experience. Semin Nucl Med. 2002;32:110–22.PubMedCrossRefGoogle Scholar
  105. Valkema R, Pauwels SA, Kvols LK, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with 90Y-DOTA0, Tyr3-octreotide and 177Lu-DOTA0, Tyr3-octreotate. J Nucl Med. 2005;46 Suppl 1:83S–91.PubMedGoogle Scholar
  106. Valkema R, Pauwels S, Kvols LK, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0, Tyr3]octreotide in patients with advanced gastroentero-pancreatic neuroendocrine tumors. Semin Nucl Med. 2006;36:147–56.PubMedCrossRefGoogle Scholar
  107. Van Den Bossche B, Van de Wiele C. Receptor imaging in oncology by means of nuclear medicine: current status. J Clin Oncol. 2004;22:3593–607.CrossRefGoogle Scholar
  108. van Essen M, Krenning EP, De Jong M, et al. Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol. 2007a;46:723–34.PubMedCrossRefGoogle Scholar
  109. van Essen M, Krenning EP, Bakker WH, et al. Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin. Eur J Nucl Med Mol Imaging. 2007b;34:1219–27.PubMedCrossRefGoogle Scholar
  110. Vincent JP, Mazella J, Kitabgi P. Neurotensin and neurotensin receptors. Trends Pharmacol Sci. 1999;20:302–9.PubMedCrossRefGoogle Scholar
  111. Virgolini I, Raderer M, Kurtaran A, et al. 123I-vasoactive intestinal peptide (VIP) receptor scanning: update of imaging results in patients with adenocarcinomas and endocrine tumors of the gastrointestinal tract. Nucl Med Biol. 1996;23:685–92.PubMedCrossRefGoogle Scholar
  112. Waldherr C, Pless M, Maecke HR, et al. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol. 2001;12:941–5.PubMedCrossRefGoogle Scholar
  113. Waldherr C, Pless M, Maecke HR, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq 90Y-DOTATOC. J Nucl Med. 2002;43:610–6.PubMedGoogle Scholar
  114. Walsh JH. Gastrointestinal hormones. In: Johnson LR, editor. Physiology of the gastrointestinal tract. 3rd ed. New York: Raven Press, Ltd; 1994. p. 1–128.Google Scholar
  115. Wang L, Shi J, Kim YS, et al. Improving tumor-targeting capability and pharmacokinetics of 99mTc-labeled cyclic RGD dimers with PEG4 linkers. Mol Pharm. 2009;6:231–45.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Wegener KL, Campbell ID. Transmembrane and cytoplasmic domains in integrin activation and protein-protein interactions (review). Mol Membr Biol. 2008;25:76–87.CrossRefGoogle Scholar
  117. Wei L, Butcher C, Miao Y, et al. Synthesis and biologic evaluation of 64Cu-labeled rhenium-cyclized α-MSH peptide analog using a cross-bridged cyclam chelator. J Nucl Med. 2007a;48:64–72.PubMedGoogle Scholar
  118. Wei L, Miao Y, Gallazzi F, et al. Gallium-68-labeled DOTA-rhenium-cyclized α-melanocyte-stimulating hormone analog for imaging of malignant melanoma. Nucl Med Biol. 2007b;34:945–53.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Wicki A, Wild D, Storch D, et al. [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 is a highly efficient radiotherapeutic for glucagon-like peptide-1 receptor-targeted therapy for insulinoma. Clin Cancer Res. 2007;13:3696–705.PubMedCrossRefGoogle Scholar
  120. Wild D, Macke H, Christ E, et al. Glucagon-like peptide 1-receptor scans to localize occult insulinomas. N Engl J Med. 2008;359:766–8.PubMedCrossRefGoogle Scholar
  121. Wild D, Christ E, Caplin ME, et al. Glucagon-like peptide-1 versus somatostatin receptor targeting reveals 2 distinct forms of malignant insulinomas. J Nucl Med. 2011;52:1073–8.PubMedCrossRefGoogle Scholar
  122. Yoshimoto M, Ogawa K, Washiyama K, et al. αvβ3 Integrin-targeting radionuclide therapy and imaging with monomeric RGD peptide. Int J Cancer. 2008;123:709–71.PubMedCrossRefGoogle Scholar
  123. Yusta B, Huang L, Munroe D, et al. Enteroendocrine localization of GLP-2 receptor expression in humans and rodents. Gastroenterology. 2000;119(3):744–55.PubMedCrossRefGoogle Scholar
  124. Zecchinon L, Fett T, Baise E, Desmecht D. Characterization of the caprine (Capra hircus) beta-2 integrin CD18-encoding cDNA and identification of mutations potentially responsible for the ruminantspecific virulence of Mannheimia haemolytica. Mol Membr Biol. 2004;21:289–95.PubMedCrossRefGoogle Scholar
  125. Zhang H, Chen J, Waldherr C, et al. Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors. Cancer Res. 2004;64:6707–15.PubMedCrossRefGoogle Scholar
  126. Zhang H, Schuhmacher J, Waser B, et al. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours. Eur J Nucl Med Mol Imaging. 2007;34:1198–208.PubMedCrossRefGoogle Scholar
  127. Zheng DQ, Woodard AS, Fornaro M, et al. Prostatic carcinoma cell migration via αvβ3 integrin is modulated by a focal adhesion kinase pathway. Cancer Res. 1999;59:655–1664.Google Scholar
  128. Zhou X, Murphy FR, Gehdu N. Engagement of αvβ3 integrin regulates proliferation and apoptosis of hepatic stellate cells. J Biol Chem. 2004;20279:23996–4006.CrossRefGoogle Scholar

Copyright information

© Springer India 2016

Authors and Affiliations

  • F. F. (Russ) Knapp
    • 1
  • Ashutosh Dash
    • 2
  1. 1.Nuclear Security and Isotope DivisionOak Ridge National LaboratoryOAK RIDGEUSA
  2. 2.Isotope Production and Applications DivisionBhabha Atomic Research CentreMumbaiIndia

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