Peptide receptor radionuclide therapy: An overview

Cancer Biotherapy and Radiopharmaceuticals

Volumn 30, Issue 2, 2015, Pages 47-71

  Dash, Ashutosh ^a   Chakraborty, Sudipta ^a   Pillai, Maroor Raghavan Ambikalmajan ^b   Knapp, Furn F Russ ^c  

^a BHABHA ATOMIC RESEARCH CENTRE   (India)

^b Molecular Group of Companies   (India)

^c OAK RIDGE NATIONAL LABORATORY   (United States)

Author keywords

111In; 177Lu; 90Y; angiogenesis; bombesin; CCK; cytotoxic; GLP; neuroendocrine tumour; NT; PRRT; radionuclide therapy; RGD; somatostatin; therapeutic radionuclide; VIP

Indexed keywords

ARGINYLGLYCYLASPARTIC ACID; BOMBESIN; CHOLECYSTOKININ; GLUCAGON LIKE PEPTIDE; INDIUM 111; LUTETIUM 177; PENTETATE INDIUM IN 111; PEPTIDE; RADIOISOTOPE; SOMATOSTATIN; SOMATOSTATIN RECEPTOR; TETULOMAB TETRAXETAN LUTETIUM LU 177; VASOACTIVE INTESTINAL POLYPEPTIDE; YTTRIUM 90; RADIOPHARMACEUTICAL AGENT; RECEPTOR;

HUMAN; ISOTOPE LABELING; NEUROENDOCRINE TUMOR; NONHUMAN; PEPTIDE LIBRARY; PEPTIDE RECEPTOR RADIONUCLIDE THERAPY; PEPTIDE SYNTHESIS; PRIORITY JOURNAL; RADIOISOTOPE THERAPY; RECEPTOR BINDING; REVIEW; ANIMAL; NEOPLASMS;

ANIMALS; HUMANS; NEOPLASMS; RADIOISOTOPES; RADIOPHARMACEUTICALS; RECEPTORS, PEPTIDE;

EID: 84924567876     PISSN: 10849785     EISSN: 15578852     Source Type: Journal    
DOI: 10.1089/cbr.2014.1741     Document Type: Review

References (219)

1. Chatal JF, Hoefnagel CA. Radionuclide therapy. Lancet 1999; 354: 931.
2. Joensuu H, Tenhunen M. Physical and biological targeting of radiotherapy. Acta Oncol Suppl 1999; 38: 75.
3. McDougall IR. Systemic radiation therapy with unsealed radionuclides. Semin Radiat Oncol 2000; 10: 94.
4. Volkert WA, Hoffman TJ. Therapeutic radiopharmaceuticals. Chem Rev 1999; 99: 2269.
5. Britton KE. Towards the goal of cancer-specific imaging and therapy. Nucl Med Commun 1997; 18: 992.
6. Heeg MJ, Jurisson S. The role of inorganic chemistry in the development of radiometal agents for cance therapy. Acc Chem Res 1999; 32: 1053.
7. Okarvi SM. Peptide-based radiopharmaceuticals: Future tools for diagnostic imaging of cancers and other diseases. Med Res Rev 2004; 24: 357.
8. Heppeler A, Froidevaux S, Eberle AN, et al. Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem 2000; 7: 971.
9. 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.
10. Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003; 24: 389.
11. Reubi JC, Macke HR, Krenning EP. Candidates for peptide receptor radiotherapy today and in the future. J Nucl Med 2005; 46 (suppl 1): 67S.
12. Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med 2006; 36: 228.
13. Reubi JC. Neuropeptide receptors in health and disease: The molecular basis for in vivo imaging. J Nucl Med 1995; 36: 1825.
14. Jakubke HD. Peptides. Heidelberg, Germany: Spektrum Akademischer Verlag, 1996; 319.
15. König W. Peptide and Protein Hormones: Structure, Regulation, Activity; a Reference Manual. Weinheim, Germany: VCH, 1993.
16. Cescato R, Schulz S, Waser B, et al. Internalization of sst2, sst3 and sst5 receptors: Effects of somatostatin agonists and antagonists. J Nucl Med 2006; 47: 502.
17. Waser B, Tamma ML, Cescato R, et al. Highly efficient in vivo agonist-induced internalization of sst2 receptors in somatostatin target tissues. J Nucl Med 2009; 50: 936.
18. Ginj M, Zhang H, Waser B, et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. PNAS 2006; 103: 16436.
19. Cescato R, Waser B, Fani M, et al. Evaluation of 177Lu- DOTA-sst2 antagonist versus 177Lu-DOTA-sst2 agonist binding in human cancers in vitro. J Nucl Med 2011; 52: 1.
20. Cescato R, Maina T, Nock B, et al. Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J Nucl Med 2008; 49: 318.
21. 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.
22. Miao Y, Benwell K, Quinn TP. 99mTc- and 111In-labeled a-melanocyte-stimulating hormone peptides as imaging probes for primary and pulmonary metastatic melanoma detection. J Nucl Med 2007; 48: 73.
23. 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.
24. 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.
25. 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; 19: 595.
26. Naik R, Stone M, Carter D. Method of isolating binding peptides from a combinatorial phase display library and peptides produced thereby. US Patent (Publication no. US20060035223 A1), 2006.
27. Srivastava SC. Paving the way to personalized medicine: Production of some promising theragnostic radionuclides at Brookhaven National Laboratory. Semin Nucl Med 2012; 42: 151.
28. 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.
29. 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.
30. 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.
31. Lahiri S, Maiti M, Ghosh K. Production and separation of 111In: An important radionuclide in life sciences: A mini review. J Radioanal Nucl Chem 2013; 297: 309.
32. McDonalds NS, Neely HH, Wood RA, et al. Methods for compact cyclotron production of In-111 for medical use. Int J Appl Radiat Isot 1975; 26: 631.
33. Zaitseva NG, Knotek O, Kowalew A, et al. Excitation functions and yields for 111In production using 113,114,natCd (p,xn)111In reaction with 65 MeV protons. Appl Radiat Isot 1990; 41: 177-183.
34. Thakur ML, Nunn AD. Cyclotron produced In-111 for medical use. Int J Appl Radiat Isot 1972; 23: 139.
35. Das SK, Guin R, Saha SK. Carrier-Free Separation of 111In from a silver Matrix Appl Radiat Isot 1996; 47: 293.
36. Das MK, Chattopadhayay S, Sarkar BR, et al. A cation exchange method for separation of 111In from inactive silver, copper, traces of iron and radioactive gallium and zinc Isotopes. Appl Radiat Isot 1997; 48: 11.
37. Chattopadhyay S, Das MK, Sarkar BR, et al. Radiochemical separation of high purity 111In from cadmium, copper, aluminium and traces of iron: Use of a cation exchange resin with hydrobromic acid. Appl Radiat Isot 1997; 48: 1063.
38. Filoosofov DV, Lebedev NA, Novogrodov A, et al. Production, concentration and deep purification of 111In radiochemicals. Appl Radiat Isot 2001; 55: 293.
39. Wood RA, Wakakuwa ST, McDonalds NS. The carrier free isolation of indium from silver and cadmium by liquid-liquid extraction. J Inorg Nucl Chem 1972; 34: 3517.
40. Das T, Pillai MRA. Options to meet the future global demand of radionuclides for radionuclide therapy. Nucl Med Biol 2013; 40: 23.
41. Banerjee S, Das T, Chakraborty S, et al. Emergence and present status of Lu-177 in targeted radiotherapy: The Indian scenario. Radiochim Acta 2012; 100: 115.
42. Pillai MRA, Chakraborty S, Das T, et al. Production logistics of 177Lu for radionuclide therapy. Appl Radiat Isot 2003; 59: 109.
43. Mikolajczak R, Parus JL, Pawlak D, et al. Reactor produced 177Lu of specific activity and purity suitable for medical applications. J Radioanal Nucl Chem 2003; 257: 53.
44. Nir-El Y. Production of 177Lu by neutron activation of 176Lu. J Radioanal Nucl Chem 2004; 262: 563.
45. Dvorakova Z, Henkelmann R, Lin X, et al. Production of 177Lu at the new research reactor FRM-II: Irradiation yield of 176Lu (n,gamma)177Lu. Appl Radiat Isot 2008; 66: 147.
46. Zhernosekov KP, Perego RC, Dvorakova Z, et al. Target burn-up corrected specific activity of 177Lu produced via 176Lu (n, gamma) 177Lu nuclear reactions. Appl Radiat Isot 2008; 66: 1218.
47. Chinol M, Cutler CS, Papi S, et al. Production of GMPcompliant lutetium-177: Radiochemical precursor for targeted cancer therapy. Nucl Med Biol 2010; 37: p717.
48. Chakraborty S, Vimalnath KV, Lohar SP, et al. On the practical aspects of large-scale production of 177Lu for peptide receptor radionuclide therapy using direct neutron activation of 176Lu in a medium flux research reactor: The Indian experience. J Radioanal Nucl Chem 2014; 302: 233.
49. Chakravarty R, Das T, Dash A, et al. An electroamalgamation approach to isolate no-carrier-added 177Lu fromneutron irradiated Yb for biomedical applications. Nucl Med Biol 2010; 37: 811.
50. Mirzadeh S, Du M, Beets AL, et al. Method for preparing high specific activity 177Lu. United States Patent 6716353, 2004.
51. Horwitz EP, Mc Alister DR, Bond AH, et al. A process for the separation of 177Lu from neutron irradiated 176Yb targets. Appl Radiat Isot 2005; 63: 23.
52. Hashimoto K, Matsuoka H, Uchida S. Production of nocarrier- added 177Lu via the 176Yb (n,g)177Yb/177Lu process 2003. J Radioanal Nucl Chem 2003; 255: 575.
53. Lebedev NA, Novgorodov AF, Misiak R, et al. Radiochemical separation of no-carrier-added 177Lu as produced via the 176Yb (n,g)177Yb/177Lu process. Appl Radiat Isot 2000; 53: 421.
54. Bilewicz A, Zuchowska K, Bartos B. Separation of Yb as YbSO4 from 176Yb target for production of 177Lu via the 176Yb (n, g)177Yb/177Lu process. J Radioanal Nucl Chem 2009; 280: 167.
55. Knapp FF Jr., Mirzadeh S, Beets AL, et al. Production of therapeutic radioisotopes in ORNL High Flux Research Reactor (HFIR) for applications in nuclear medicine, oncology and interventional cardiology. J Radioanal Nucl Chem 2005; 263: 503.
56. So LV, Morcos N, Zaw M, et al. Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation, Part I. Multi-column chromatographic process for clinically applicable. J Radioanal Nucl Chem 2008; 277: 663.
57. Morcos N, Zaw M, Pellegrini P, et al. Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation Part II. The conventional column chromatographic separation combined with HPLC for high purity. J Radioanal Nucl Chem 2008; 277: 675.
58. Kumric K, Trtic-Petrovic T, Koumarianou E, et al. Supported liquid membrane extraction of 177Lu (III) with DEHPA and its application for the purification of 177Lu- DOTA-lanreotide. Sep Purif Technol 2006; 51: 310.
59. Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re generators. IAEA Technical Report Series No. 470, IAEA, Vienna, 2009.
60. Chakravarty R, Dash A, Pillai MR. Availability of yttrium-90 from stroncium-90: A nuclear medicine prespective. Cancer Biother Radiopharm 2012,27: 621.
61. Abbasi IA, Zaidi JH, Arif M, et al. Measurement of fission neutron spectrum averaged cross sections of some threshold reactions on zirconium: Production possibility of no-carrier-added 90Y in a nuclear reactor. Radiochim Acta 2006; 94: 381.
62. Production of long lived parent radionuclides for generators: 68Ge, 82Sr, 90Sr and 188W. IAEA Radioisotopes and Radiopharmaceuticals Series No. 2, IAEA, Vienna, 2010.
63. Wester DW, Steele RT, Rinehart DE, et al. Large-scale purification of 90Sr from nuclear waste materials for production of 90Y, a therapeutic medical radioisotope. Appl Radiat Isot 2003; 59: 35.
64. Beard SJ, Moore RL. Large-scale recovery and purification of fission products. In: Stevenson CE, Mason EA, Gresky AT (eds.), Progress in Nuclear Energy (Series III), Process Chemistry, Vol 4. London, United Kingdom: Pergamon Press, 1969; 645.
65. Bray LA. The recovery and purification of multi-kilocurie quantities of fission product strontium by cation exchange. Rep. HW-70998, Hanford Atomic Products Operation, Richland, WA, 1961.
66. Orth RJ, Kurath DE. Review and assessment of technologies for the separation of strontium from alkaline and acidic media. Rep. PNL-9053, Pacific Northwest National Laboratory, Richland, WA, 1994.
67. Horwitz EP, Dietz ML, Fisher DE. SREX: A new process for the extraction and recovery of strontium from acidic nuclear waste streams. Solv Extr Ion Exch 1991; 9: 1.
68. Lumetta GJ, Wester DW, Morrey JR, et al. Preliminary evaluation of chromatographic techniques for the separation of radionuclides from high level radioactive waste. Solv Extr Ion Exch 1993; 11: 663.
69. Wike JS, Guyer CE, Ramey DW, et al. Chemistry for commercial-scale production of yttrium-90 for medical research. Appl Radiat Isot 1990; 41: 861.
70. Hsieh BT, Ting G, Hsieh HT, et al. Preparation of carrierfree yttrium-90 for medical applications by solvent extraction chromatography. Appl Radiat Isot 1993; 44: 1473.
71. Castillo AX, Pérez-Malo M, Isaac-Olivé K, et al. Production of large quantities of 90Y by ion-exchange chromatography using an organic resin and a chelating agent. Nucl Med Biol 2010; 37: 935.
72. Naik PW, Jagasia P, Dhami PS, et al. Separation of carrierfree 90Y from 90Sr by SLM technique using D2EHPA in n-dodecane as carrier. Sep Sci Technol 2010; 45: 554.
73. Lee JS, Park UJ, Son KJ, et al. One column operation for 90Sr/90Y separation by using a functionalized-silica. Appl Radiat Isot 2009; 67: 1332.
74. Dhami PS, Naik PW, Dudwadkar NL, et al. Studies on the development of a two stage SLM system for the separation of carrier-free 90Y using KSM-17 and CMPO as carriers. Sep Sci Technol 2007; 42: 1107.
75. Bray LA. Method for separating and purifying Yttrium-90 from Strontium-90. U.S. Patent US2006/0018813 A1, 2006.
76. Betenekov ND, Sharygin LM, Brown RW. Sr-90/Y-90 radionuclide generator for production of high quality Y-90 solution. U.S. Patent US 7,101,484 B2, 2006.
77. Chakravarty R, Pandey U, Manolkar RB, et al. Development of an electrochemical 90Sr-90Y generator for the separation of 90Y suitable for targeted therapy. Nucl Med Biol 2008; 35: 245.
78. Montaña RL, González IH, Ramirez AA, et al. Yttrium-90- current status, expected availability and applications of a high beta energy emitter. Curr Radiopharm 2012; 5: 253.
79. Kamadhenu Electrochemical 90Sr/90Y generator, Model KA 01 Operating Manual. Dresden, Germany: Isotope Technologies, 2010.
80. Pandey U, Dhami PS, Jagesia P, et al. A novel extraction paper chromatography (EPC) technique for the radionuclidic purity evaluation of 90Y for clinical use. Anal Chem 2008; 80: 801.
81. Fani M, Maecke HR, Okarvi SM. Radiolabeled peptides: Valuable tools for the detection and treatment of cancer. Theranostics 2012; 2: 481.
82. Liu S, Edwards DS. Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconjug Chem 2001; 12: 7.
83. Liu S. Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides. Adv Drug Deliv Rev 2008; 60: 1347.
84. Bartholomä MD. Recent developments in the design of bifunctional chelators for metal-based radiopharmaceuticals used in Positron Emission Tomography. Inorg Chim Acta 2012; 389: 36.
85. Chakraborty S, Liu S. (99m)Tc and (111)In-labeling of small biomolecules: Bifunctional chelators and related coordination chemistry. Curr Top Med Chem 2010; 10: 1113.
86. Stimmel JB, Kull FC Jr. Samarium-153 and lutetium-177 chelation properties of selected macrocyclic and acyclic ligands. Nucl Med Biol 1998; 25: 117.
87. León-Rodríguez LMD, Kovacs Z. The synthesis and chelation chemistry of DOTA-peptide conjugates. Bioconjug Chem 2008; 19: 391.
88. Brechbiel MW. Bifunctional chelates for metal nuclides. Q J Nucl Med Mol Imaging 2008; 52: 166.
89. Liu S. The role of coordination chemistry in the development of target specific radiopharmaceuticals. Chem Soc Rev 2004; 33: 445.
90. Chakravarty R, Chakraborty S, Dash A. A systematic comparative evaluation of 90Y-labeled bifunctional chelators for their use in targeted therapy. J Label Compd Radiopharm 2014; 57: 65.
91. Okarvi SV. Recent developments in 99mTc-labelled peptidebased radiopharmaceuticals. Nucl Med Commun 1999; 20: 1093.
92. Faintuch BL, Pereira NPS, Faintuch S, et al. Direct labeling studies of octapeptides with rhenium-188. Radiochim Acta 2003; 91: 427.
93. Gali H, Hoffman TJ, Sieckman GL, et al. Synthesis, characterization, and labeling with 99mTc/188Re of peptide conjugates containing a dithia-bisphosphine chelating agent. Bioconjug Chem 2001; 12: 354.
94. 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.
95. 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.
96. Schonbrunn A. Somatostatin receptors present knowledge and future directions. Ann Oncol 1999; 10 (Supplement 2): S17.
97. de Herder WW, Hofland LJ, Lely AJ, et al. Somastostatin receptors in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer 2003; 10: 451.
98. Hoyer D, Bell GI, Berelowitz M, et al. Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci 1995; 16: 86.
99. Reubi JC, Schaer JC, Markwalder R, et al. Distribution of somatostatin receptors in normal and neoplastic human tissues: Recent advances and potential relevance. Yale J Biol Med 1997; 70: 471.
100. Reubi JC. Somatostatin and other peptide receptors as tools for tumor diagnosis and treatment. Neuroendocrinology 2004; 80 (Supplement 1): 51.
101. 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.
102. Reubi JC, Schar JC, Waser B, et al. Affinity profiles of human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000; 27: 273.
103. ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors Part 1 and Part 2. Neuroendocrinology 2006; 84: 151 and 2008; 87: 1.
104. Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9: 61-72.
105. Oberg K. Carcinoid tumors: Molecular genetics, tumor biology, and update of diagnosis and treatment. Curr Opin Oncol 2002; 14: 38.
106. Oberg K. Future aspects of somatostatin-receptor mediated therapy. Neuroendocrinology 2004; 80 (Suppl. 1): 57.
107. 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.
108. Reubi JC, Korner M, Waser B, et al. High expression of peptide receptors as a novel target in gastrointestinal stromal tumours. Eur J Nucl MedMol Imaging 2004; 31: 803.
109. 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.
110. Anthony LB, Woltering EA, Espanan GD, et al. Indium-111- pentetreotide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med 2002; 32: 123.
111. Kaltsas GA, Papadogias D, Makras P, et al. Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues. Endocr Relat Cancer 2005; 12: 683.
112. 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.
113. De Jong M, Breeman WAP, Kwekkeboom DJ, et al. Tumor imaging and therapy using radiolabeled somatostatin analogues. Acc Chem Res 2009; 42: 873.
114. Kam BLR, Teunissen JJM, Krenning EP, et al. Lutetiumlabeled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2012; 39 (suppl 1): S103.
115. Otte A, Mueller-Brand J, Dellas S, et al. Yttrium-90- labelled somatostatin-analogue for cancer treatment. Lancet 1998; 351: 417.
116. 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.
117. Kao YH, Tan AEH, Lo RHG, et al. Non-target activity detection by post-radioembolization yttrium-90 PET/CT: Image assessment technique and case examples. Front Oncol 2014; 4: 11.
118. Cutler CS, Hennkens HM, Sisay N, et al. Radiometals for combined imaging and therapy. Chem Rev 2013; 113: 858.
119. Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate: Toxicity, efficacy, and survival. J Clin Oncol 2008; 26: 2124.
120. van Essen M, Krenning EP, Bakker WH, et al. Peptidereceptor radionuclide therapy with 177Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin. Eur J NuclMed Mol Imaging 2007; 34: 1219.
121. 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 2007; 46: 723.
122. Jong M, Valkema R, Jamar F, et al. Somatostatin receptortargeted radionuclide therapy of tumors: Preclinical and clinical findings. Semin Nucl Med 2002; 32: 133.
123. Kunikowska J, Krolicki L, Hubalewska-Dydejczyk A, et al. 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: 1788.
124. Wild ED, Fani M, Behe M, et al. First clinical evidence that imaging with somatostatin receptor antagonists is feasible. J Nucl Med 2011; 52: 1.
125. Bunnett G. Gastrin-releasing peptide. In: Walsh JH, Dockray GJ (eds.), Gut Peptides: Biochemistry and Physiology. New York, NY: Raven Press Ltd, 1994; 423-445.
126. Walsh JH. Gastrointestinal hormones. In: Johnson LR (ed.), Physiology of the Gastrointestinal Tract. New York, NY: Raven Press Ltd, 1994; 1-128.
127. Gonzalez N, Moody TW, Igarashi H, et al. Bombesinrelated peptides and their receptors: Recent advances in their role in physiology and disease states. Curr Opin Endocrinol Diabetes Obes 2008; 15: 58.
128. Ohki-Hamazaki H, Iwabuchi M, Maekawa F. Development and function of bombesin-like peptides and their receptors. Int J Dev Biol 2005; 49: 293.
129. 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.
130. Zhang H, Chen J, Waldherr C, et al. Synthesis and evaluation of bombesin derivatives on the basis of panbombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors. Cancer Res 2004; 64: 6707.
131. 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.
132. 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.
133. 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 radiopharmaceutical for PC-3 human prostate cancer cells. Nucl Med Biol 2003; 30: 101.
134. 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.
135. Igarashi H, Ito T, Mantey SA, et al. Development of simplified vasoactive intestinal peptide analogs with re-ceptor selectivity and stability for human vasoactive intestinal pep-tide/pituitary adenylate cyclase-activating polypeptide receptors. J Pharmacol Exp Ther 2005; 315: 370.
136. 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.
137. 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.
138. Nock BA, Maina T, Behe M, et al. CCK-2/gastrin receptortargeted tumor imaging with 99mTc-labeled minigastrin analogs. J Nucl Med 2005; 46: 1727.
139. Brans B, Linden O, Giammarile F, et al. Clinical applications of newer radionuclide therapies. Eur J Cancer 2006; 42: 994.
140. 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.
141. Laverman P, Joosten L, Eek A, et al. Comparative biodistribution of 12 111In-labelled gastrin/CCK2 recep-tor-targeting peptides. Eur J Nucl Med Mol Imaging 2011; 38: 1410.
142. Behr TM, Behe MP. Cholecystokinin-B/Gastrin receptortargeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptorexpressing malignancies. Semin Nucl Med 2002; 32: 97.
143. Roosenburg S, Laverman P, van Delft FL, et al. Radiolabeled CCK/gastrin peptides for imaging and therapy of CCK2 receptor-expressing tumors. Amino Acids 2011; 41: 1049.
144. Tanaka K, Masu M, Nakanishi S. Structure and functional expression of the cloned rat neurotensin receptor. Neuron 1990; 4: 847.
145. Vincent JP, Mazella J, Kitabgi P. Neurotensin and neurotensin receptors. Trends Pharmacol Sci 1999; 20: 302.
146. de Visser M, Janssen PJJM, Srinivasan A, et al. Stabilised 111In-labelled DTPA- and DOTA-conjugated neurotensin analogues for imaging and therapy of exocrine pancreatic cancer. Eur J Nucl Med Mol Imaging 2003; 30: 1134.
147. Mayo KE, Miller LJ, Bataille D, et al. International Union of Pharmacology. XXXV. The glucagon receptor family. Pharmacol Rev 2003; 55: 167.
148. Drucker DJ. Minireview: The glucagon-like peptides. Endocrinology 2001; 142: 521.
149. 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.
150. Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: Molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging 2003; 30: 781.
151. 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.
152. Meier JJ, Nauck MA. Glucagon-like peptide 1 (GLP-1) in biology and pathology. Diabetes Metab Res Rev 2005; 21: 91.
153. 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.
154. Wicki A, Wild D, Storch D, et al. [Lys40 (Ahx- DTPA-111In)NH2]-Exendin-4 is a highly efficient radiothera- peutic for glucagon-like peptide-1 receptor-targeted therapy for insu-linoma. Clin Cancer Res 2007; 13: 3696.
155. 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.
156. 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.
157. 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.
158. 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.
159. 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.
160. 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.
161. Jain RK. Transport of molecules in the tumor interstitium: A review. Cancer Res 1987; 47: 3039-3051.
162. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med 2000; 6: 389-395.
163. Francavilla C, Maddaluno L, Cavallaro U. The functional role of cell adhesion molecules in tumor angiogenesis. Semin Cancer Biol 2009; 19: 298.
164. Tei K, Kawakami-kiumra N, Taguchi O, et al. Roles of cell adhesion molecules in tumor angeiogenesis by cotransplantation of tumor and endothelial cells to nude rats. Cancer Res 2002; 62: 6289.
165. Hwang R, Varner JV. The role of integrins in tumor angiogenesis. Hematol Oncol Clin North Am 2004; 18: 991.
166. Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 2008; 8: 604.
167. Liu S. Radiolabeled multimeric cyclic RGD peptides as integrin avb3 targeted radiotracers for tumor imaging. Mol Pharm 2006; 3: 472.
168. Brooks PC, Clark RAF, Cheresh DA. Requirement of vascular integrin avb3 for angiogenesis. Science 1994; 264: 569.
169. Horton MA. The avb3 integrin ''vitronectin receptor.'' Int J Biochem Cell Biol 1997; 29: 721.
170. Kumar CC. Integrin avb3 as a therapeutic target for blocking tumor-induced angiogenesis. Curr Drug Targets 2003; 4: 123.
171. Miyata S, Koshikawa N, Yasumitsu H, et al. Trypsin stimulates integrin a5b1-dependent adhesion to fibronectin and proliferation of human gastric carcinoma cells through activa-tion of proteinase-activated receptor-2. J Biol Chem 2000; 275: 4592.
172. 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 a2b1 integrin and PDGFb receptor. Biochem Biophys Res Commun 2004; 325: 328.
173. Zhou X, Murphy FR, Gehdu N, et al. Engagement of avb3 integrin regulates proliferation and apoptosis of hepatic stellate cells. J Biol Chem 2004; 279: 23996.
174. Hynes RO. Integrins: Bidirectional, allosteric signaling machines. Cell 2002; 110: 673.
175. 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.
176. Desgrosellier JS, Cheresh DA. Integrins in cancer: Biological implications and therapeutic opportunities. Nat Rev Cancer 2010; 10: 9.
177. Guo W, Giancotti FG. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol 2004; 5: 816.
178. Chung J, Yoon SO, Lipscomb EA, et al. The Met receptor and a6b4 integrin can function independently to promote carcinoma invasion. J Biol Chem 2004; 279: 32287.
179. Burke PA, DeNardo SJ. Antiangiogenic agents and their promising potential in combined therapy. Crit Rev Oncol Hematol 2001; 39: 155.
180. Tucker GC. Integrins: Molecular targets in cancer therapy. Curr Oncol Rep 2006; 8: 96.
181. Millard M, Odde S, Neamati N. Integrin targeted therapeutics. Theranostics 2011; 1: 154.
182. Nissinen L, Pentikäinen OT, Jouppila A, et al. A smallmolecule inhibitor of integrin a2b1 introduces a new strategy for antithrombotic therapy. Thromb Haemost 2010; 103: 387.
183. Lal H, Verma SK, Foster DM, et al. Integrins and proximal signaling mechanisms in cardiovascular disease. Front Biosci 2009; 14: 2307.
184. Stefanelli T, Malesci A, De La Rue SA, et al. Antiadhesion molecule therapies in inflammatory bowel disease: Touch and go. Autoimmun Rev 2008; 7: 364.
185. Hilden TJ, Nurmi SM, Fagerholm SC, et al. Interfering with leukocyte integrin activation - A novel concept in the development of anti-inflammatory drugs. Ann Med 2006; 38: 503.
186. Danhier F, Le Breton A, Préat V. RGD-based strategies to target alpha (v) beta (3) integrin in cancer therapy and diagnosis. Mol Pharm 2012; 9: 2961.
187. Dijkgraaf I, Kruijtzer JAW, Liu S, et al. Improved targeting of the avb3 integrin by multimerization of RGD peptides. Eur J Nucl Med Mol Imaging 2007; 34: 267.
188. Temming K, Schiffelers RM, Molema G, et al. RGD based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist Updat 2005; 8: 381.
189. Chen X. Multimodality imaging of tumor integrin avb3 expression. Mini Rev Med Chem 2006; 6: 227.
190. Cai W, Niu G, Chen X. Imaging of integrins as biomarkers for tumor angiogenesis. Curr Pharm Des 2002; 14: 2943.
191. Janssen M, Oyen WJ, Massuger LF, et al. Comparison of a monomeric and dimeric radiolabeled RGD-peptide for tumor targeting. Cancer Biother Radiopharm 2002; 17: 641.
192. Chen XY, Tohme M, Park R, et al. MicroPET imaging of breast cancer av-integrin expression with 18F-labeled dimeric RGD peptide. Mol Imaging 2004; 3: 96.
193. Janssen ML, Oyen WJG, Dijkgraaf I, et al. Tumor targeting with radiolabeled avb3 integrin binding peptides in a nude mouse model. Cancer Res 2002; 62: 6146.
194. Wu Y, Zhang XZ, Xiong ZM, et al. MicroPET imaging of glioma av-integrin expression using 64Cu-labeled tetrameric RGD peptide. J Nucl Med 2005; 46: 1707.
195. Liu S, Hsieh WY, Jiang Y, et al. Evaluation of a 99mTclabeled cyclic RGD tetramer for noninvasive imaging integrin avb3-positive breast cancer. Bioconjug Chem 2007; 18: 438.
196. Liu S. Radiolabeled cyclic RGD peptides as integrin avb3 targeted radiotracers: Maximizing binding affinity via bivalency. Bioconjug Chem 2009; 20: 2199.
197. Haubner R, Wester HJ, Reuning U, et al. Radiolabeled avb3 integrin antagonists: A new class of tracers for tumor imaging. J Nucl Med 1999; 40: 1061.
198. Zhou Y, Kim Y-S, Chakraborty S, et al. 99mTc-labeled cyclic RGD peptides for noninvasive monitoring of tumor integrin avb3 expression. Mol Imaging 2011; 10: 386.
199. Beer AJ, Haubner R, Goebel M, et al. Biodistribution and pharmacokineticss of the avb3-selective tracer 18F-Galacto- RGD in cancer patients. J Nucl Med 2005; 46: 1333.
200. Chen X, Liu S, Hou Y, et al. MicroPET imaging of breast cancer av-integrin expression with 64Cu-labeled dimeric RGD peptides. Mol Imaging Biol 2004; 6: 350.
201. Li ZB, Chen K, Chen X. 68Ga-labeled multimeric RGD peptides for microPET imaging of integrin avb3 expression. Eur J Nucl Med Mol Imaging 2008; 35: 1100.
202. Liu Z, Liu S, Wang F, et al. Noninvasive imaging of tumor integrin expression using 18F-labeled RGD dimer peptide with PEG4 linkers. Eur J Nucl Med Mol Imaging 2009; 36: 1296.
203. Shi J, Wang L, Kim YS, et al. Improving tumor uptake and excretion kinetics of 99mTc-labeled cyclic arginine-glycineaspartic (RGD) dimers with triglycine linkers. J Med Chem 2008; 51: 7980.
204. Shi J, Kim YS, Zhai S, et al. Improving tumor uptake and pharmacokinetics of 64Cu-labeled cyclic RGD peptide dimers with Gly3 and PEG4 linkers. Bioconjug Chem 2009; 20: 750.
205. Dijkgraaf I, Yim CB, Franssen GM, et al. PET imaging of avb3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides. Eur J Nucl Med Mol Imaging 2010; 37: 1615.
206. Chakraborty S, Shi J, Kim YS, et al. Evaluation of 111Inlabeled cyclic RGD peptides: Tetrameric not tetravalent. Bioconjug Chem 2011; 21: 969.
207. Liu Z, Wang F, Chen X. Integrin targeted delivery of radiotherapeutics. Theranostics 2011; 1: 201.
208. Liu Z, Shi J, Jia B, et al. Two 90Y-labeled multimeric RGD peptides RGD4 and 3PRGD2 for integrin targeted radionuclide therapy. Mol Pharm 2011; 8: 472.
209. Shi J, Liu Z, Jia B, et al. Potential therapeutic radiotracers: Preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer. Amino Acids 2010; 39: 111.
210. Luna-Gutiérrez M, Ferro-Flores G, Ocampo-García B, et al. 177Lu-labeled monomeric, dimeric and multimeric RGD peptides for the therapy of tumors expressing a (v)b (3) integrins. J Label Compd Radiopharm 2012; 50: 140.
211. Chakraborty S, Sarma HD, Vimalnath KV, et al. Tracer level radiochemistry to clinical dose preparation of 177Lulabeled cyclic RGD peptide dimer. Nucl Med Biol 2013; 40: 946.
212. Chakraborty S, Chakravarty R, Sarma HD, et al. Utilization of a novel electrochemical 90Sr/90Y generator for the preparation of 90Y-labeled RGD peptide dimer in clinically relevant dose. Radiochim Acta 2014; 102: 523.
213. Vaidyanathan G, Boskovitz A, Shankar S, et al. Radioiodine and 211At labeled guadinomethyl halobenzyl octreotate conjugates: Potential peptide therapeutics for somtaostatin receptor positive cancers. Peptides 2004; 25: 2087.
214. Miederer M, Henriksen G, Alke A, et al. Preclinical evaluation of the a-particle generator nuclide 225Ac for somatostatin receptor radiotherapy of neuroendocrine tumors. Clin Cancer Res 2008; 14: 3555.
215. Nayak TK, Norenberg JP, Anderson TL, et al. Somatostatin- receptor-targeted alpha-emitting 213Bi is therapeutically more effective than beta ( - )-emitting 177Lu in human pancreatic adenocarcinoma cells. Nucl Med Bio 2007; 35: 185.
216. Lewington VJ. Targeted radionuclide therapy for neuroendocrine tumors. Endocr Relat Cancer 2003; 10: 497.
217. Ma D, McDevitt MR, Finn RD, et al. Breakthrough of 225Ac and its radionuclide daughters from an 225Ac/213Bi generator: Development of new methods, quantitative characterization, and implications for clinical use. Appl Radiat Isot 2001; 55: 667.
218. Lehenberger S, Barkhausen C, Cohrs S, et al. The lowenergy b- and electron emitter 161Tb as an alternative to 177Lu for targeted radionuclide therapy. Nucl Med Biol 2011; 38: 917.
219. Cremonesi M, Ferrari M, Bodei L, et al. Dosimetry in peptide radionuclide receptor therapy: A review. J Nucl Med 2006; 47: 1467.