Skip to main content
SpringerLink
Log in

Radiolabeled Peptides in Oncology

Role in Diagnosis and Treatment

  • Drug Development
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

There has been an exponential growth in the development of radiolabeled peptides for diagnostic and therapeutic applications in the last decade. The automated means of synthesizing these compounds in large quantities and the simplified methods of purifying, characterizing, and optimizing them have kindled attention to peptides as carrier molecules. These new techniques have accelerated the commercial development of radiolabelled peptides, which has provided additional radiopharmaceuticals for the nuclear medicine community.

Peptides have many key properties including fast clearance, rapid tissue penetration, and low antigenicity, and can be produced easily and inexpensively. However, there may be problems with in vivo catabolism, unwanted physiologic effects, and chelate attachment. Radiolabeled peptides have made their greatest impact in the management of relatively rare neuroendocrine malignancies. Indeed, Indium-111 (111In)-pentetreotide (111In-DTPA-octreotide, Octreoscan®), which binds to somatostatin receptors (SSTRs), has become the diagnostic ‘gold standard’ in these diseases. However, 111In-pentetreotide has been less successful in the diagnosis of other more prevalent diseases in which SSTRs are upregulated. Technetium-99m (99mTc)-depreotide (NeoTect™), a 99mTc-labeled SSTR-analog, could have wider impact since it has high sensitivity and specificity for lung cancer lesion detection. However, this impact may be minimized by the increased availability of positron emission tomography imaging with Fluorine-18 (18F)-flourodeoxyglucose, which has similar sensitivity and specificity for lesion identification in this disease, and is currently more widely used. The receptors for bombesin, α-melanocyte-stimulating hormone, neurotensin, and the integrin αvβ3, are under active investigation as targets for radiolabelled peptides, but are still in the pre-clinical stage. Compounds directed at the cholecystokinin-B/gastrin receptor have shown promising results in clinical trials in humans.

Radiolabelled peptide therapy is usually indicated for patients with widespread disease that is not amenable to focused radiation therapy or is refractory to chemotherapy. Phase I/II studies using various radiolabelled peptides (including 111In-pentetreotide, Yttrium-90 [90Y]-DOTA-Phe1-Tyr3-octreotide, 90Y-DOTA-lanreotide, and Lutetium-177 [177Lu]-DOTA-octreotate) for the treatment of patients with neuroendocrine malignancy are in progress. Over 400 patients have been treated, and the response rate has ranged from 60% to 75%, although few patients have had a complete response. Patients have been given individual doses ranging from 2 to 11 GBq with a slow infusion every 4–8 weeks (up to 12 times). The kidney is the dose-limiting organ and most patients experience a transient decline in blood cell counts. A concomitant infusion of an amino acid mixture can reduce kidney toxicity and increase the effective tumor dose. Other peptides currently under investigation, some of which have shown promising results, include Rhenium-188 (188Re)-P2045 and 90Y-αvβ3 antagonist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Fig. 2
Table II
Fig. 3
Table III
Fig. 4
Fig. 5
Fig. 6
Table IV
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Krenning EP, Bakker WH, Breeman WA, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989; 4: 242–4

    Article  Google Scholar 

  2. Kwekkeboom DJ, Krenning EP, de Jong M. Peptide receptor imaging and therapy. J Nucl Med 2000; 41: 1704–13

    PubMed  CAS  Google Scholar 

  3. Kwekkeboom DJ, Krenning EJ, de Jong M. Somatostatin receptor scintigraphy. In: Sandier MP, Coleman RE, Wackers F, et al., editors. Diagnostic nuclear medicine. 4th ed. Baltimore (MD): Lippincott Williams & Wilkins, 2003: 735–46

    Google Scholar 

  4. Balon HR, Goldsmith SJ, Siegel BA, et al. Procedure guideline for somatostatin receptor scintigraphy with 111In-pentetreotide. J Nucl Med 2001; 42: 1134–8

    PubMed  CAS  Google Scholar 

  5. Lamberts SWJ, Krenning E, Reubi J-C. The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr Rev 1991; 12: 450–82

    Article  PubMed  CAS  Google Scholar 

  6. Mallinckrodt Inc. OctreoScan®. Kit for the preparation of indium In-111 pentetreotide diagnostic [online]. Available from URL: http://imaging.mallinckrodt.com/_Attachments/PackageInserts/Octreoscan%20PI.pdf [Accessed 2005 May11]

  7. Froidevaux S, Eberle AN. Somatostatin analogs and radiopeptides in cancer therapy. Biopolymers 2002; 66: 161–83

    Article  PubMed  CAS  Google Scholar 

  8. McAfee JG, Neumann RD. Radiolabeled peptides and other ligands for receptors overexpressed in tumor cells for imaging neoplasms. Nucl Med Biol 1996; 23: 673–6

    Article  PubMed  CAS  Google Scholar 

  9. Reubi JC. Neuropeptide receptors in health and disease: the molecular basis for in vivo imaging. J Nucl Med 1995; 36: 1825–35

    PubMed  CAS  Google Scholar 

  10. Heasly LE. Autocrine and paracrine signaling through neuropeptide receptors in human cancer. Oncogene 2001; 20: 1563–9

    Article  CAS  Google Scholar 

  11. Moody TW, Chan D, Fahrenkrug J, et al. Neuropeptides as autocrine growth factors in cancer cells. Curr Pharm Des 2003; 9: 495–509

    Article  PubMed  CAS  Google Scholar 

  12. Okarvi SM. Recent developments in 99Tcm-labelled peptide-based radiopharmaceuticals: an overview. Nucl Med Commun 1999; 20: 1093–112

    Article  PubMed  CAS  Google Scholar 

  13. Reubi JC. In vitro identification of vasoactive intestinal peptide receptors in human tumors: implications for tumor imaging. J Nucl Med 1995; 36: 1846–53

    PubMed  CAS  Google Scholar 

  14. Hennig IM, Laissue JA, Horisberger U, et al. Substance-P receptors in human primary neoplasms: tumoral and vascular localization. Int J Cancer 1995; 61: 786–92

    Article  PubMed  CAS  Google Scholar 

  15. Hua C, Shu XX, Lei C. Pancreatoblastoma: a histochemical and immunohistochemical analysis. J Clin Pathol 1996; 49: 952–4

    Article  PubMed  CAS  Google Scholar 

  16. Koikov LN, Ebetino FH, Solinsky MG, et al. Sub-nanomolar hMC1R agonists by end-capping of the melanocortin tetrapeptide His-D-Phe-Trp-NH2. Med Chem Lett 2003; 13: 2647–50

    Article  CAS  Google Scholar 

  17. NeoTect package insert. Londonderry (NH): Diatide, 1999

  18. AcuTect. Package insert. Londonderry (NH): Diatide, 1998

  19. Blum JE, Handmaker H, Lister-James J, et al. A multicenter trial with a somatostatin analogue (99m)Tc depreotide in the evaluation of solitary pulmonary nodules. Chest 2000; 117: 1232–8

    Article  PubMed  CAS  Google Scholar 

  20. Fisher BMB, Mortensen J, Højgaard L. Positron emission tomography in the diagnosis and staging of lung cancer: a systematic, quantitative review. Lancet Oncol 2001; 2: 659–66

    Article  Google Scholar 

  21. Ho Shon I, O’Doherty MJ, Maisey MN. Positron emission tomography in lung cancer. Semin Nucl Med 2002; 32: 240–71

    Article  PubMed  Google Scholar 

  22. McGilvery RW. Biochemistry: a functional approach. 2nd ed. Philadelphia (PA): WB Saunders, 1983

    Google Scholar 

  23. Fujimori K, Covell DG, Fletcher JE, et al. A modeling analysis of monoclonal antibody percolation through tumors: a binding-site barrier. J Nucl Med 1990; 31: 1191–8

    PubMed  CAS  Google Scholar 

  24. Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res 1987; 47: 3039–51

    PubMed  CAS  Google Scholar 

  25. Dean RT, James JL, Lees RS, et al. Peptides in biomedical sciences: principles and practice. In: Martin-Comin J, Thakur ML, Piera C, et al., editors. Radiolabeled blood elements. New York (NY): Plenum Press, 1994: 195–9

    Chapter  Google Scholar 

  26. Thakur ML, Kolan HR, Rifat S, et al. Vapreotide labeled with Tc-99m for imaging tumors: preparation and preliminary evaluation. Int J Oncol 1996; 9: 445–51

    PubMed  CAS  Google Scholar 

  27. Baidoo KE, Lin K-S, Zhan Y, et al. Design, synthesis, and initial evaluation of high-affinity technetium bombesin analogues. Bioconjug Chem 1998; 10: 218–25

    Article  Google Scholar 

  28. Qu T, Wang Y, Zhu Z, et al. Different chelators and different peptides together influence the in vivo properties of 99Tcm. Nucl Med Commun 2001; 22: 203–15

    Article  PubMed  CAS  Google Scholar 

  29. Pallela VR, Consigny M, Patti R, et al. Thrombospondin analog Tc-99m-TP-1201 for imaging thrombosis. J Lab Comp Radiopharm 1997; 40: 452–4

    Google Scholar 

  30. Pallela VR, Thakur ML, Chakder S, et al. 99mTc-labeled vasoactive intestinal peptide receptor agonist: functional studies. J Nucl Med 1999; 40: 352–60

    PubMed  CAS  Google Scholar 

  31. Thakur ML, Marcus CS, Saeed S, et al. 99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans. J Nucl Med 2000; 41: 107–10

    PubMed  CAS  Google Scholar 

  32. Rao PS, Pallela VR, Vassileva-Belnikolavska DV, et al. A receptor specific peptide for imaging infection and inflammation. Nucl Med Commun 2000; 21: 1063–70

    Article  PubMed  CAS  Google Scholar 

  33. Rao PS, Thakur ML, Pallela V, et al. 99mTc labeled VIP analog: evaluation for imaging colorectal cancer. Nucl Med Biol 2001; 28: 445–50

    Article  PubMed  CAS  Google Scholar 

  34. Haubner R, Wester H-J, Burkhart F, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med 2001; 42: 326–36

    PubMed  CAS  Google Scholar 

  35. Jensen RT. Natural history of digestive endocrine tumors. In: Mignon M, Colombel JF, editors. Recent advances in the pathophysiology and management of inflammatory bowel diseases and digestive endocrine tumors. Paris: John Libbey Eurotext, 1999: 192–219

    Google Scholar 

  36. Caplin ME, Buscombe JR, Hilson AJ, et al. Carcinoid tumour. Lancet 1998; 352: 799–805

    Article  PubMed  CAS  Google Scholar 

  37. Yu F, Venzon DJ, Serrano J, et al. Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome. J Clin Oncol 1999; 17: 615–30

    PubMed  CAS  Google Scholar 

  38. Holland LJ, Lamberts SWJ. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 2003; 24: 28–47

    Article  CAS  Google Scholar 

  39. Hung PD, Schubert ML, Mihas AA. Zollinger-Ellison Syndrome. Curr Treat Options Gastroenterol 2003; 6: 163–70

    Article  PubMed  Google Scholar 

  40. Chamberlain RS, Canes D, Brown KT, et al. Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg 2000; 190: 432–45

    Article  PubMed  CAS  Google Scholar 

  41. Gibril F, Reynolds JC, Chen CC, et al. Specificity of somatostatin receptor scintigraphy: a prospective study and effects of false-positive localizations on management in patients with gastrinomas. J Nucl Med 1999; 40: 539–53

    PubMed  CAS  Google Scholar 

  42. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1] and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993; 20: 716–31

    Article  PubMed  CAS  Google Scholar 

  43. Krenning EP, Kwekkeboom DJ, Pauwels S, et al. Somatostatin receptor scintigraphy. Nucl Med Ann 1995: 1–5

  44. Breeman WAP, van Hagen PM, Kwekkeboom DJ, et al. Somatostatin receptor scintigraphy using [111In-DTPA0]RC-160 in humans: a comparison with [111In-DTPA0]octreotide. Eur J Nucl Med 1998; 25: 182–6

    Article  PubMed  CAS  Google Scholar 

  45. Andersson P, Forssell-Aronsson E, Johanson V, et al. Internalization of Indium-111 into human neuroendocrine tumor cells after incubation with Indium-111-DTPA-D-Phe. J Nucl Med 1996; 37(12): 2002–6

    PubMed  CAS  Google Scholar 

  46. Hornick CA, Anthony CT, Hughey S, et al. Progressive nuclear translocation of somatostatin analogs. J Nucl Med 2000; 41: 1256–63

    PubMed  CAS  Google Scholar 

  47. Janson ET, Westlin J-E, Ohrvall U, et al. Nuclear localization of 111In after intravenous injection of [111In-DTPA-D-Phe1]-octreotide in patients with neuroendocrine tumors. J Nucl Med 2000; 41: 1514–8

    PubMed  CAS  Google Scholar 

  48. Traub T, Petkov V, Ofluoglu S, et al. 111In-DOTA-lanreotide scintigraphy in patients with tumors of the lung. J Nucl Med 2001; 42: 1309–15

    PubMed  CAS  Google Scholar 

  49. Adams S, Baum RP, Hertel A, et al. Intraoperative gamma probe detection of neuroendocrine tumors. J Nucl Med 1998; 39: 1155–60

    PubMed  CAS  Google Scholar 

  50. Weiner RE, Thakur ML. Radiolabeled peptides in diagnosis and therapy. Semin Nucl Med 2001; 31: 296–311

    Article  PubMed  CAS  Google Scholar 

  51. van Eijck CH, de Jong M, Breeman WA, et al. Somatostatin receptor imaging and therapy of pancreatic endocrine tumors. Ann Oncol 1999; 10: 1777–81

    Google Scholar 

  52. Forssell-Aronsson EB, Nilsson O, Benjegård SA, et al. 111In-DTPA-D-Phe1 octreotide binding and somatostatin receptor subtypes in thyroid tumors. J Nucl Med 2000; 41: 636–42

    PubMed  CAS  Google Scholar 

  53. Gibril F, Reynolds JC, Doppman JL, et al. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. Ann Intern Med 1996; 125: 26–34

    PubMed  CAS  Google Scholar 

  54. Lebtahi R, Cadiot G, Sarda L, et al. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J Nucl Med 1997; 38: 853–8

    PubMed  CAS  Google Scholar 

  55. Chiti A, Briganti V, Fanti S, et al. Results and potential of somatostatin receptor imaging in gastroenteropancreatic tract tumours. Q J Nucl Med 2000; 44: 42–9

    PubMed  CAS  Google Scholar 

  56. Schillaci O, Spanu A, Scopinaro F, et al. Somatostatin receptor scintigraphy in liver metastasis detection from gastroenteropancreatic neuroendocrine tumors. J Nucl Med 2003; 44: 359–68

    PubMed  CAS  Google Scholar 

  57. Panzuto F, Falconi M, Nasoni S, et al. Staging of digestive endocrine tumours using helical computed tomography and somatostatin receptor scintigraphy. Ann Oncol 2003; 14: 586–91

    Article  PubMed  CAS  Google Scholar 

  58. Joseph K, Stapp J, Reinecke J, et al. Receptor scintigraphy with 111In-pentetreotide for endocrine gastroenteropancreatic tumors. Horm Metab Res 1993; 27: 28–35

    CAS  Google Scholar 

  59. Gotthardt M, Dirkmorfeld LM, Wied MU, et al. Influence of somatostatin scanning on the therapeutic management of patients with advanced gastrointestinal neuroendocrine tumors in comparison to CT and MRI [abstract]. J Nucl Med 2003a; 44: 383P

    Google Scholar 

  60. Pfannenberg AC, Eschmann SM, Horger M, et al. Benefit of anatomical-functional image fusion in the diagnostic work-up of neuroendocrine neoplasms. Eur J Nucl Med 2003; 30: 835–43

    Article  Google Scholar 

  61. Lugtenburg PJ, Löwenberg B, Valkema R, et al. Somatostatin receptor scintigraphy in the initial staging of low-grade non-Hodgkin’s lymphomas. J Nucl Med 2001; 42: 222–9

    PubMed  CAS  Google Scholar 

  62. Flamen P, Bossuyt A, De Greve J, et al. Imaging of renal cell cancer with radiolabelled octreotide. Nucl Med Commun 1993; 14: 873–7

    Article  PubMed  CAS  Google Scholar 

  63. Lipp RW, Silly H, Ranner G, et al. Radiolabeled octreotide for the demonstration of somatostatin receptors in malignant lymphoma and lymphadenopathy. J Nucl Med 1995; 36: 13–8

    PubMed  CAS  Google Scholar 

  64. van Eijck CHJ, Krenning EP, Bootsma A, et al. Somatostatin-receptor scintigraphy in primary breast cancer. Lancet 1994; 343: 640–3

    Article  PubMed  Google Scholar 

  65. Kirsch C-M, von Pawel J, Grau I, et al. Indium-111 pentetreotide in the diagnostic work-up of patients with bronchogenic carcinoma. Eur J Nucl Med 1994; 21: 1318–25

    Article  PubMed  CAS  Google Scholar 

  66. O’Byrne KJ, Halmos G, Pinski J, et al. Somatostatin receptor expression in lung cancer. Eur J Cancer 1994; 30A: 1682–7

    Article  PubMed  Google Scholar 

  67. Kwekkeboom DJ, Kho GS, Lamberts SWJ, et al. The value of Octreotide scintigraphy in patients with lung cancer. Eur J Nucl Med 1994; 21: 1106–13

    Article  PubMed  CAS  Google Scholar 

  68. Reisinger I, Bohuslavitzki KH, Brenner W, et al. Somatostatin receptor scintigraphy in small-cell lung cancer: results of a multicenter study. J Nucl Med 1998; 39: 224–7

    PubMed  CAS  Google Scholar 

  69. Virgolini I, Leimer M, Handmaker H, et al. Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829. Cancer Res 1998a; 58: 1850–9

    CAS  Google Scholar 

  70. Grewal RK, Dadparvar S, Yu JQ, et al. Efficacy of Tc-99m depreotide scintigraphy in the evaluation of solitary pulmonary nodules. Cancer J 2002; 8: 400–4

    Article  PubMed  Google Scholar 

  71. Bridwell RS, Montilla J. Sequential SPECT Tc-99m depreotide: can we improve specificity [abstract]? J Nucl Med 2003; 44: 383P

    Google Scholar 

  72. Gambhir SS, Czernin J, Schwimmer J, et al. A tabulated summary of the FDG PET literature. J Nucl Med 2001; 42: 1S–93S

    PubMed  CAS  Google Scholar 

  73. Chan DC, Waxman AD, Williams CM, et al. Comparison of FDG-PET and Tc-99m depreotide in the evaluation of patients with proven lung cancer [abstract]. J Nucl Med 2003; 44: 135P

    Google Scholar 

  74. Virgolini I, Szilvasi I, Kurtaran A, et al. Indium-111-DOTA-Lanreotide: biodistribution, safety and radiation absorbed dose in tumor patients. J Nucl Med 1998; 39: 1928–36

    PubMed  CAS  Google Scholar 

  75. Smith-Jones PM, Bischof C, Leimer M, et al. DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy. Endocrinology 1999; 140: 5136–48

    Article  PubMed  CAS  Google Scholar 

  76. Reubi JC, Schär J-C, Waser B, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000; 27: 273–82

    Article  PubMed  CAS  Google Scholar 

  77. Weiner RE, Thakur ML. Chemistry of gallium and indium radiopharmaceuticals. In: Welch M, Redvanly C, editors. Handbook of radiopharmaceuticals: radiochemistry and applications. West Sussex (UK): John Wiley Publishers, 2003: 363–99

    Google Scholar 

  78. Albert R, Smith-Jones P, Stolz B, et al. Direct synthesis of [DOTA-D-Phe1-Tyr3]-Octreotide (SMT487): two conjugates for the systemic delivery of radiotherapeutical nuclides to somatostatin receptor positive tumors in man. Bioorg Med Chem Lett 1998; 8: 1207–10

    Article  PubMed  CAS  Google Scholar 

  79. Henze M, Schumacher J, Hipp P, et al. PET imaging of somatostatin receptors using [68Ga]-DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med 2001; 42: 1053–6

    PubMed  CAS  Google Scholar 

  80. Hofman M, Maecke H, Börner AR, et al. Biokinetics and imaging with somatostatin receptors PET radioligand 68Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001; 28: 1751–7

    Article  CAS  Google Scholar 

  81. Virgolini I, Kurtaran A, Raderer M, et al. Vasoactive intestinal peptide receptor scintigraphy. J Nucl Med 1995; 36: 1732–9

    PubMed  CAS  Google Scholar 

  82. Raderer M, Kurtaran A, Yang Q, et al. Iodine-123-vasoactive intestinal peptide receptor scanning in patients with pancreatic cancer. J Nucl Med 1998; 39: 1570–5

    PubMed  CAS  Google Scholar 

  83. Virgolini I, Raderer M, Kurtaran A, et al. Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors. N Engl J Med 1994; 331: 1116–21

    Article  PubMed  CAS  Google Scholar 

  84. Raderer M, Kurtaran A, Leimer M, et al. Value of peptide receptor scintigraphy using 123I-vasoactive intestinal peptide and min-DTPA-D-Phe1-octreotide in 194 carcinoid patients: Vienna University experience, 1993 to 1998. J Clin Oncol 2000; 18: 1331–6

    PubMed  CAS  Google Scholar 

  85. Raderer M, Becherer A, Kurtaran A, et al. Comparison of Iodine-123-vasoactive intestinal peptide receptor scintigraphy and Indium-111-CYT-103 immunoscintigraphy. J Nucl Med 1996; 37: 1480–7

    PubMed  CAS  Google Scholar 

  86. Thakur ML, Marcus CS, Saeed S, et al. Imaging tumors in humans with Tc-99M-VIP. Ann N Y Acad Sci 2000; 921: 37–44

    Article  PubMed  CAS  Google Scholar 

  87. Virgolini I, Traub T, Ofluoglu S, et al. Human biodistribution, safety and absorbed dose of 99mTc-P1666 vasoactive intestinal peptide (VIP) receptor scintigraphy [abstract]. J Nucl Med 1999; 40: 244P

    Google Scholar 

  88. Reubi JC, Schär J-C, Waser B. Cholecystokinin (CCK)-A and CCK-B/gastrin receptors in human tumors. Cancer Res 1997; 57: 1377–86

    PubMed  CAS  Google Scholar 

  89. Béhé M, Behr TM. Cholecystokinin-B (CCK-B)/gastrin receptor targeting peptides for staging and therapy of medullary thyroid cancer and other CCK-B receptor expressing malignancies. Biopolymers 2002; 66: 399–418

    Article  PubMed  CAS  Google Scholar 

  90. Behr TM, Jenner N, Béhé M, et al. Radiolabeled peptides for targeting cholecystokinin-B/gastrin receptor-expressing tumors. J Nucl Med 1999; 40: 1029–44

    PubMed  CAS  Google Scholar 

  91. Gotthardt M, Behe MP, Schipper ML, et al. In-111-DTPA-D-Glu1-minigastrin used for therapy of metastatic medullary thyroid carcinoma and other neuroendocrine tumors: results of an ongoing dose-escalation study [abstract]. J Nucl Med 2003; 44: 137P

    Google Scholar 

  92. Laverman P, Behe M, Behr TM, et al. Synthesis and characterization of 99mTc-labeled Hynic-conjugated sulfated and nonsulfated Cholecystokinin-8 (CCK-8) [abstract]. J Nucl Med 2003; 44: 97P

    Google Scholar 

  93. Behr TM, Béhé MP, Angerstein C, et al. Cholecystokinin (CCK)-B/gastrin-receptor binding peptides for diagnosis and therapy of metastatic medullary thyroid cancer [abstract]. J Nucl Med 2001; 42: 157P

    Google Scholar 

  94. Behr TM, Béhé M, Angerstein C, et al. Development of cholecystokinin-B/gastrin-receptor binding peptides for diagnosis and therapy: results of a clinical phase-I/II study for the staging of known and occult metastatic medullary thyroid cancer [abstract]. Nucl Med Commun 2000; 21: 564–5

    Article  Google Scholar 

  95. Behr TM, Jenner N, Radetzky S. Targeting of cholecystokinin-B/gastrin receptors in vivo: preclinical and initial clinical evaluation of the diagnostic and therapeutic potential of radiolabelled gastrin. Eur J Nucl Med 1998; 25: 424–30

    Article  PubMed  CAS  Google Scholar 

  96. de Jong M, Bakker WH, Bernard BF, et al. Preclinical and initial clinical evaluation of 111In-labeled nonsulfated CCK8 analog: a peptide for CCK-B receptor-targeted scintigraphy and radionuclide therapy. J Nucl Med 1999; 40: 2081–7

    PubMed  Google Scholar 

  97. Raj GV, Partin AW, Polascik TJ. Clinical utility of Indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy. Cancer 2002; 94: 987–96

    Article  PubMed  Google Scholar 

  98. Cytogen Corp. ProstaScint product information [online]. Available from URL: http://www.cytogen.com/professional/prostascint/pi.php [Accessed 2005 May 8]

  99. Luu A, Lin KS, Gargari H, et al. 99mTc(CO)3-[DTPA0, Glu1, LyS3, Tyr4]BN: a new bombesin analog for imaging bombesin receptors [abstract]. J Nucl Med 2003; 44: 99P

    Google Scholar 

  100. Nock B, Nikolopoulou A, Chiotellis E, et al. [99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging. Eur J Nucl Med 2003; 30: 247–58

    Article  CAS  Google Scholar 

  101. Breeman WAP, de Jong M, Erion JL, et al. Preclinical comparison of 111In-Labeled DTPA-or DOTA-bombesin analogs for receptor-targeted scintigraphy and radionuclide therapy. J Nucl Med 2002; 43: 1650–6

    PubMed  CAS  Google Scholar 

  102. Van de Wiele C, Dumont F, Dierckx RA, et al. Biodistribution and dosimetry of 99mXc-RP527, a gastrin-releasing peptide (GRP) agonist for the visualization of GRP receptor-expressing malignancies. J Nucl Med 2001; 42: 1722–7

    PubMed  Google Scholar 

  103. Smith CJ, Gali H, Sieckman GL, et al. Radiochemical investigations of 99mTc-N3S-X-BBN[7-14]NH2: an in vitro/in vivo structure-activity relationship study where X = 0-, 3-, 5-, 8-, and 11-carbon tethering moieties. Bioconjug Chem 2003; 14: 93–102

    Article  PubMed  CAS  Google Scholar 

  104. Reilly RM, Kiarash R, Sandhu J, et al. A comparison of EGF and MAB528 labeled with 111In for imaging human breast cancer. J Nucl Med 2000; 41: 903–11

    PubMed  CAS  Google Scholar 

  105. Capala J, Barth RF, Bailey MQ, et al. Radiolabeling of epidermal growth factor with 99mTc and in vivo localization following intracerebral injection into normal and glioma-bearing rats. Bioconjug Chem 1997; 8: 289–95

    Article  PubMed  CAS  Google Scholar 

  106. Rusckowski M, Qu T, Chang F, et al. Technetium-99m labeled epidermal growth factor-tumor imaging in mice. J Pept Res 1997; 50: 393–401

    Article  PubMed  CAS  Google Scholar 

  107. Reilly RM, Kiarash R, Cameron RG, et al. 111In-labeled EGF is selectively radiotoxic to human breast cancer cells overexpressing EGFR. J Nucl Med 2000; 41: 429–38

    PubMed  CAS  Google Scholar 

  108. van Hagen PM, Breeman WA, Bernard HF, et al. Evaluation of a radiolabeled cyclic DTPA-RGD analogue for tumor imaging and radionuclide therapy. Int J Cancer 2000; 90: 186–98

    Article  PubMed  Google Scholar 

  109. Su Z-F, Liu G, Gupta S, et al. In vitro and in vivo evaluation of a Technetium-99m-labeled cyclic RGD peptide as a specific marker of αvβ3 integrin for tumor imaging. Bioconjug Chem 2002; 13: 561–70

    Article  PubMed  CAS  Google Scholar 

  110. Janssen ML, Oyen WJ, Dijkgraaf I, et al. Tumor targeting with radiolabeled αvβ3 integrin binding peptides in a nude mouse model. Cancer Res 2002; 62: 6146–51

    PubMed  CAS  Google Scholar 

  111. Chen JQ, Cheng Z, Owen NK, et al. Evaluation of an 111In-DOTA-Rhenium cyclized α-MSH analog: a novel cyclic-peptide analog with improved tumor-targeting properties. J Nucl Med 2001; 42: 1847–55

    PubMed  CAS  Google Scholar 

  112. Froidevaux S, Calame-Christe M, Tanner H, et al. A novel DOTA-α-Melanocyte-stimulating hormone analog for metastatic melanoma diagnosis. J Nucl Med 2002; 43: 1699–706

    PubMed  CAS  Google Scholar 

  113. Bergmann R, Scheunemann M, Heichert C, et al. Biodistribution and catabolism of 18F-Iabeled neurotensin(8-13) analogs. Nucl Med Biol 2002; 29: 61–72

    Article  PubMed  CAS  Google Scholar 

  114. Hillairet de Boisferon M, Raguin O, Thiercelin C, et al. Improved tumor selectivity of radiolabeled peptides by receptor and antigen dual targeting in the neurotensin receptor model. Bioconjug Chem 2002; 13: 654–62

    Article  CAS  Google Scholar 

  115. Jenkins SA, Kynaston HG, Davies ND, et al. Somatostatin analogs in oncology: a look to the future. Chemotherapy 2001; 47: 162–96

    Article  PubMed  CAS  Google Scholar 

  116. Wiseman GA, White CA, Stabin M, et al. Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin’s lymphoma. Eur J Nucl Med 2000; 27: 766–77

    Article  PubMed  CAS  Google Scholar 

  117. Kaminski MS, Estes J, Zasadny KR, et al. Radioimmunotherapy with Iodine 131I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood 2000; 96: 1259–66

    PubMed  CAS  Google Scholar 

  118. Valkema R, Pauwels S, Kvols L, et al. Survival in patients with neuroendocrine tumors after treatment with [Y-90-DOTA,Tyr3]octreotide in a phase-1 study [abstract]. J Nucl Med 2003; 44: 136P

    Google Scholar 

  119. Bushneil D, O’Dorisio T, Menda Y, et al. Evaluating the clinical effectiveness of 90Y-SMT 487 in patients with neuroendocrine tumors. J Nucl Med 2003; 44: 1556–60

    Google Scholar 

  120. Weiner RE, Spencer RP. erapeutic use of particulate radiopharmaceuticals. In: Arshady R, editor. Radiolabeled and magnetic particles in medicine & biology. London: Citus Books, 2001: 321–60

    Google Scholar 

  121. Silvester J. Consequences of Indium-111 decay in vivo: calculated absorbed radiation dose to cells labeled by Indium-111 oxine. J Lab Comp Radiopharm 1978; 19: 196–7

    Google Scholar 

  122. Michel RB, Brechbiel MW, Mattes MJ. A comparison of 4 radionuclides conjugated to antibodies for single-cell kill. J Nucl Med 2003; 44: 632–40

    PubMed  CAS  Google Scholar 

  123. Pouget J-P, Mather SJ. General aspects of the cellular response to low- and high-LET radiation. Eur J Nucl Med 2001; 28: 541–61

    Article  PubMed  CAS  Google Scholar 

  124. Thakur ML, Coss R, Howell R, et al. Role of lipid soluble complexes in targeted tumor therapy. J Nucl Med 2003; 44: 1293–300

    PubMed  CAS  Google Scholar 

  125. Eisenwiener K-P, Prata MIM, Buschmann I, et al. NODAGATOC, a new chelator-coupled somatostatin analogue labeled with [67/68Ga] and [111In] for SPECT, PET, and targeted therapeutic applications of somatostatin receptor (hsst2) expressing tumors. Bioconjug Chem 2002; 13: 530–41

    Article  PubMed  CAS  Google Scholar 

  126. Kwekkeboom DJ, Bakker WH, Kooij PPM, et al. [177Lu-DOTA0,Tyr3]octreotide: comparison with [111In-DTPA0]octreotide in patients. Eur J Nucl Med 2001; 28: 1319–25

    Article  PubMed  CAS  Google Scholar 

  127. Buscombe JR, Caplin ME, Hilson AJW. Long-term efficacy of high-activity 111In-pentetreotide therapy in patients with disseminated neuroendocrine tumors. J Nucl Med 2003; 44: 1–6

    PubMed  CAS  Google Scholar 

  128. Valkema R, de jong M, Bakker WH, et al. Phase I of peptide receptor radionuclide therapy with [111a-DTPA0] Octreotide: the Rotterdam experience. Semin Nucl Med 2002; 32: 110–22

    Article  PubMed  Google Scholar 

  129. Anthony LB, Woltering EA, Espenan GD. Indium-111-pentetreortide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med 2002; 32: 123–32

    Article  PubMed  Google Scholar 

  130. Argiris A, Peccerillo K, Murren JR, et al. Phase I/II trial with 111In-pentetreotide in patients with advanced malignancies [abstract]. Poster presentation at the Digestive Disease Week 2000, 2748P

  131. Rolleman EJ, Valkema R, de Jong M, et al. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med 2003; 30: 9–15

    Article  CAS  Google Scholar 

  132. Gehan E, Tefft MC. Will there be resistance to the RECIST (Response Evaluation Criteria In Solid Tumor)? J Natl Cancer Int 2000; 92: 179–81

    Article  CAS  Google Scholar 

  133. Cornelius EA, Murren J, Zoghbi S, et al. In-111-octreotide therapy: phase I-II trial [abstract]. J Nucl Med 1999; 40: 18P

    Google Scholar 

  134. Krenning BJ, Konings IR, Norenberg JP, et al. Long-term histological organ damage in animals following peptide receptor radionuclide therapy (PRRT) with high doses of 90Y- and 111In-labeled [DOTA0,Tyr3]octreotide (DOTATOC) [abstract]. J Nucl Med 2001; 42: 37P

    Google Scholar 

  135. Otte A, Jermann E, Béhé M, et al. DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy. Eur J Nucl Med 1997; 24: 792–5

    PubMed  CAS  Google Scholar 

  136. Otte A, Mueller-Brand J, Dellas S, et al. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet 1998; 351: 417–8

    Article  PubMed  CAS  Google Scholar 

  137. Förster GJ, Engelbach M, Brockmann J, et al. Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of 86Y-DOTATOC and 111In-DTPA-octreotide. Eur J Nucl Med 2001; 28: 1743–50

    Article  PubMed  CAS  Google Scholar 

  138. Otte A, Hermann R, Heppeler A, et al. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 1999; 26: 1439–47

    Article  PubMed  CAS  Google Scholar 

  139. Paganelli G, Bodei L, Junak DH, et al. 90Y-DOTA-D-Phe1-Try3-Octreotide in therapy of neuroendocrine malignancies. Biopolymers 2002; 66: 393–8

    Article  PubMed  CAS  Google Scholar 

  140. Waldherr C, Pless M, Maecke H, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq 90Y-DOTATOC. J Nucl Med 2002; 43: 610–6

    PubMed  CAS  Google Scholar 

  141. Bodei L, Cremonesi M, Zoboli S, et al. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med 2003; 30: 207–16

    Article  CAS  Google Scholar 

  142. Cybulla M, Weiner SM, Otte A. End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med 2001; 28: 1552–4

    Article  PubMed  CAS  Google Scholar 

  143. Jamar F, Barone R, Mathieu I, et al. 86Y-DOTA0-D-Phe1-Tyr3-octreotide (SMT487) -a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med 2003; 30: 510–8

    Article  CAS  Google Scholar 

  144. Virgolini I, Britton K, Buscombe J, et al. 111In and 90Y-DOTA-Lanreotide: results and implications of the MAURITIUS Trial. Semin Nucl Med 2002; 32: 146–55

    Google Scholar 

  145. Buscombe JR, Caplin ME, Watkinson AJ, et al. Treating advanced liver metastases of neuroendocrine tumors with intra-hepatic artery infusions of Y-90 lanreotide [abstract]. J Nucl Med 2003b; 44: 136P

    Google Scholar 

  146. de Jong M, Breeman WAP, Bernard BF, et al. [177Lu-DOTA0,Tyr3]octreotate for somatostatin receptor-targeted radionuclide therapy. Int J Cancer 2001; 92: 628–33

    Article  PubMed  Google Scholar 

  147. Kwekkeboom DJ, Bakker WH, Kam BL, et al. Treatment of patients with gastroenteropancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med 2003; 30: 417–22

    Article  CAS  Google Scholar 

  148. Anderson CJ, Dehdashti F, Cutler PD, et al. 64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. J Nucl Med 2001; 42: 213–21

    PubMed  CAS  Google Scholar 

  149. Boring C, Squires T, Tong T. Cancer statistics. CA Cancer J Clin 1993; 43: 7–26

    Article  PubMed  CAS  Google Scholar 

  150. Mulshine JL, Tockman MS, Smart CR. Considerations in the development of lung cancer screening tools. J Natl Cancer Inst 1989; 81: 900–6

    Article  PubMed  CAS  Google Scholar 

  151. Magram MY, Edelman MJ, Forero A, et al. A novel Rhenium-188 labelled somatostatin receptor (SSTR) targeting peptide, P2045, as potential targeted therapy for lung cancer [abstract]. J Nucl Med 2003; 44: 137P

    Google Scholar 

  152. Reilly RM, Scollard DA, Wang J, et al. A kit formulated under good manufacturing practices for labeling human epidermal growth factor receptor with 111In for radiotherapeutic applications. J Nucl Med 2004; 45: 701–8

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr Dik Kwekkeboom, at the Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, Netherlands, for generously providing images of a patient undergoing therapy with 177Lu-[DOTA0-Phe1-Tyr 3] Octreotide. We would also like to thank Drs Abraham, Schleif, and Lister-James of Berlex Inc., for providing the structure of the lung cancer treatment peptide, P2045. Dr R.Weiner is a consultant to Biogen Idec, Inc. The typing assistance of James Clarkin-Breslin and Kate Musselman is gratefully acknowledged.

No sources of funding were used to assist in the preparation of this review.

Author information

Authors and Affiliations

  1. Department of Diagnostic Imaging and Therapeutics, University of Connecticut Health Center, Farmington, Connecticut, USA

    Ronald E. Weiner

  2. Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA

    Mathew L. Thakur

  3. Division of Nuclear Medicine MC-2804, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06030-2804, USA

    Ronald E. Weiner

Authors
  1. Ronald E. Weiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mathew L. Thakur
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald E. Weiner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weiner, R.E., Thakur, M.L. Radiolabeled Peptides in Oncology. BioDrugs 19, 145–163 (2005). https://doi.org/10.2165/00063030-200519030-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-200519030-00002

Keywords

Search

Navigation