Seminars in Nuclear Medicine
Volume 32, Issue 2 , Pages 97-109 , April 2002

Cholecystokinin-B/gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies

  • Thomas M. Behr

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Thomas M. Behr, MD, Department of Nuclear Medicine, Philipps-University of Marburg, Baldingerstr., D-35043 Marburg/Lahn, Germany
    • ,
  • Martin P. Béhé

References 

  1. Reubi JC, Landolt AM. High density of somatostatin receptors in pituitary tumors from acromegalic patients. J Clin Endocrinol Metab. 1984;59:1148–1151
  2. Behr TM, Béhé M, Becker W. Diagnostic applications of radiolabeled peptides in nuclear endocrinology. Q J Nucl Med. 1999;43:268–280
  3. Behr TM, Gotthardt M, Barth A, et al. Imaging tumors with peptide-based radioligands. Q J Nucl Med. 2001;45:189–200
  4. Behr TM, Goldenberg DM, Becker WS. Radioimmunotherapy of solid tumors: A review “Of Mice and Men”. Hybridoma. 1997;16:101–107
  5. Reubi JC. Regulatory peptide receptors as molecular targets for cancer diagnosis and therapy. Q J Nucl Med. 1997;41:63–70
  6. Reubi JC. Neuropeptide receptors in health and disease: The molecular basis for in vivo imaging. J Nucl Med. 1995;36:1825–1835
  7. Lamberts SW, Koper JW, Reubi JC. Potential role of somatostatin analogues in the treatment of cancer. Eur J Clin Invest. 1987;17:281–287
  8. Krenning EP, Kwekkeboom DJ, Pauwels S, et al. Somatostatin receptor scintigraphy. In: Freeman LM editors. Nuclear Medicine Annual 1995. New York, NY: Raven Press; 1995;p. 1–50
  9. Krenning EP, Bakker WH, Breeman WA, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet. 1989;1:242–244
  10. Lamberts SW, Bakker WH, Reubi JC, et al. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med. 1990;323:1246–1249
  11. 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;20:716–731
  12. Krenning EP, Kwekkeboom DJ, Oei HY, et al. Somatostatin-receptor scintigraphy in gastro-enteropancreatic tumors. An overview of European results. Ann N Y Acad Sci. 1994;733:416–424
  13. Cerulus G, Lenoard JP. A comparison of 111In-octreotide and 67Ga scintigraphy in malignant lymphoma. Nucl Med Commun. 1997;18:616–622
  14. Ivancevic V, Wörmann B, Nauck C, et al. Somatostatin receptor scintigraphy in the staging of lymphomas. Leuk Lymphoma. 1997;26:107–114
  15. Behr TM, Gratz S, Markus PM, et al. Anticarcinoembryonic antigen antibodies versus somatostatin analogs in the detection of metastatic medullary thyroid carcinoma: Are carcinoembryonic antigen and somatostatin receptor expression prognostic factors?. Cancer. 1997;80:2436–2457
  16. Bohuslavizki KH, Brenner W, Gunther M, et al. Somatostatin receptor scintigraphy in the staging of small cell lung cancer. Nucl Med Commun. 1996;17:191–196
  17. 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;331:1116–1121
  18. Hennig IM, Laissue JA, Horisberger U, et al. Substance P receptors in human primary neoplasms. Int J Cancer. 1995;61:786–792
  19. Van Hagen PM, Breeman WAP, Reubi JC, et al. Visualization of the thymus by substance P receptor scintigraphy in man. Eur J Nucl Med. 1996;23:1508–1513
  20. Otte A, Mueller-Brand J, Dellas S, et al. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet. 1998;351:417–418
  21. 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;12:941–945
  22. Breeman WA, de Jong M, Kwekkeboom DJ, et al. Somatostatin receptor-mediated imaging and therapy: Basic science, current knowledge, limitations and future perspectives. Eur J Nucl Med. 2001;28:1421–1429
  23. Krenning EP, de Jong M. Therapeutic use of radiolabelled peptides. Ann Oncol. 2000;11(suppl 3):267–271
  24. Smith-Jones PM, Bischof C, Leimer M, et al. DOTA-lanreotide: A novel somatostatin analog for tumor diagnosis and therapy. Endocrinology. 1999;140:5136–5148
  25. Paganelli G, Zoboli S, Cremonesi M, et al. Recptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide. Eur J Nucl Med. 2001;28:434
  26. Behr TM, Sharkey RM, Juweid ME, et al. Reduction of the renal uptake of radiolabeled monoclonal antibody fragments by cationic amino acids and their derivatives. Cancer Res. 1995;55:3825–3834
  27. De Jong M, Rolleman EJ, Bernard BF, et al. Inhibition of renal uptake of indium-111-DTPA-octreotide in vivo. J Nucl Med. 1996;37:1388–1392
  28. Behr TM, Goldenber DM, Becker W. Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: Present status, future prospects and limitations. Eur J Nucl Med. 1998;25:201–212
  29. Behr TM, Beeker W. Imaging in meduallary thyroid cancer. In: Biersack HJ, Grünwald F editor. Thyroid Cancer. Berlin: Springer-Verlag; 2001;p. 251–273
  30. Hazard JB, Hawk WA, Crile G. Medullary (solid) carcinoma of the thyroid: A clinicopathological entity. J Clin Endocrinol Metab. 1959;19:152
  31. Pearse AG. The calcitonin secreting C cells and their relationship to the APUD cell series. J Endocrinol. 1969;45:13–14
  32. Pears AG. Common cytochemical properties of cells producing polypeptide hormones, with particular reference to calcitonin and the thyroid C cells. Vet Rec. 1966;79:587–590
  33. Williams ED. Histogenesis of medullary carcinoma of the thyroid. J Clin Pathol. 1966;19:114
  34. Wells SA, Baylin SB, Linehan WM, et al. Provocative agents and the diagnosis of medullary carcinoma of the thyroid gland. Ann Surg. 1978;188:139
  35. Pacini F, Basolo F, Elisei R, et al. Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens. Am J Clin Pathol. 1991;95:300–308
  36. Becker W, Spiegel W, Reiners C, et al. Besonderheiten bei der Nachsorge des C-Zell-Karzinons. Nuklearmediziner. 1986;9:167–181
  37. Samaan NA, Schultz PN, Hickey RC. Medullary thyroid carcinoma: Prognosis of familial versus sporadic disease and the role of radiotherapy. J Clin Endocrinol Metal. 1988;67:801–808
  38. O'Riordain DS, O'Brien T, Weaver AL, et al. Medullary thyroid carcinoma in multiple endocrine neoplasia types 2A and 2B. Surgery. 1994;116:1017
  39. Pacini F, Fontanelli M, Fugazzola L, et al. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab. 1994;78:826–829
  40. Bergholm U, Bergström R, Ekbom A. Long-term follow-up of patients with medullary carcinoma of the thyroid. Cancer. 1997;79:132–138
  41. Kameda Y, Ikeda K, Ikeda A. Uptake of radioiodine in follicles of dog C-cell complexes studied by autoradiograph and immunoperoxidase staining. Anat Rec. 1981;200:461–470
  42. Jensen RT. Overview of chronic diarrhea caused by functional neuroendocrine neoplasms. Semin Gastrointest Dis. 1999;10:156–172
  43. Behr TM, Becker W. Erhöhte Serum-CEA-Spiegel als Erstmanifestation eines medullären Schilddrüsenkarzinomas. Dtsch Med Woehenschr. 1999;124:303–304
  44. Behr TM, Gratz S, Markus PM, et al. Enhanced bilateral somatostatin receptor expression in mediastinal lymph nodes (“chimney sign”) in occult metastatic medullary thyroid cancer: A typical sign of tumor manifestation. Eur J Nucl Med. 1997;24:184–191
  45. Behr TM, Becker W. Metabolic and receptor imaging of metastatic medullary thyroid cancer. Does anti-CEA and somatostatin-receptor scintigraphy allow for diagnostic predictions. Eur J Nucl Med. 1999;26:70–71
  46. Juweid ME, Sharkey RM, Behr T, et al. Radioimmunotherapy of medullary thyroid carcinoma with 131I-labeled anti-CEA antibodies. J Nucl Med. 1996;37:875–881
  47. Behr TM, Wulst E, Radezky S, et al. Improved treatment of medullary thyroid cancer in a nude mouse model by combined radioimmunochemotherapy: Doxorubicin potentiates the therapeutic efficacy of radiolabeled antibodies in a radioresistant tumor type. Cancer Res. 1997;57:5309–5319
  48. Hajjar G, Sharkey RM, Burton J, et al. Interim results of an ongoing phase I trial for the treatment of medullary thyroid cancer with radioimmunotherapy combined with doxorubicin. J Nucl Med. 2001;42(suppl):157P–158P
  49. Bläker M, de Weerth A, Tometten M, et al. Expression of the CCK2-receptor in normal human thyroid gland and medullary thyroid carcinoma. Eur J Endocrinol. 2002;146:89–96
  50. Reubi JC, Waser B. Unexpected high incidence of cholecystokinin/gastrin receptors in human medullary thyroid carcinomas. Int J Cancer. 1996;67:644–647
  51. Reubi JC, Schaer JC, Waser B. Cholecystokinin (CCK)-A and CCK-B/gastrin receptors in human tumors. Cancer Res. 1997;57:1377–1386
  52. Weinberg DS, Ruggeri B, Barber MT, et al. Cholecystokinin A and B receptors are differently expressed in normal pancreas and pancreatic adenocarcinoma. J Clin Invest. 1997;100:597–603
  53. Behr TM, Jenner N, Radetzky S, et al. Targeting of cholecystokinin-B/gastrin receptors in vivo: Preclinical and initial clinical evaluation of the diagnostic and therapeutic potential of radiolabeled gastrin. Eur J Nucl Med. 1998;25:424–430
  54. Behr TM, Jenner N, Béhé M, et al. Radiolabeled peptides for targeting of cholecystokinin-B/gastrin, receptor expressing tumors: From preclinical development to initial clinical results. J Nucl Med. 1999;40:1029–1044
  55. Behr TM, Béhé M, Angerstein G, et al. Cholecystokinin-B/gastrin receptor binding peptides: Preclinical development and evaluation of their diagnostic and therapeutic potential. Clin Cancer Res. 1999;5:3124–3138
  56. Béhé M, Behr TM, Angerstein C, et al. Stabilized DTPA chelator as an alternative to the DOTA chelator exemplified with minigastrin. J Nucl Med. 2000;41(suppl):120p
  57. Behr TM, Béhé MP, Angerstein C, et al. Radiopeptide therapy with cholecystokinin (CCK)-B/gastrin receptor ligands: Toxicity and theraputic efficacy of Auger e− versus α or β emitters. J Nucl Med. 2001;42(suppl):68P
  58. Béhé M, Becker W, Behr TM. Internalisation properties of 111In-DTPA-d-Glu1-minigastrin. Eur J Nucl Med. 2001;28:968
  59. 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;40:2081–2087
  60. Kwekkeboom DJ, Bakker WH, Kooij PP, et al. Cholecystokinin receptor imaging using an octapeptide DTPA-CCK analogue in patients with medullary thyroid carcinoma. Eur J Nucl Med. 2000;27:1312–1317
  61. Behr TM, Béhé MP, Angerstein C, et al. Cholecystokinin (CCK)-B/gastrin-receptor binding peptides for diagnosis and therapy of metastatic medullary thyroid cancer. J Nucl Med. 2001;42(suppl):157P
  62. Schmitz F, Otte JM, Stechele HU, et al. CCK-B/gastrin receptors in human colorectal cancer. Eur J Clin Invest. 2001;31:812–820
  63. Smith AM, Watson SA. Gastrin and gastrin receptor activation: An early event in the adenoma-carcinoma sequence. Gut. 2000;47:820–824
  64. Hellmich MR, Rui XL, Hellmich HL, et al. Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth. J Biol Chem. 2000;275:32122–32128
  65. Kermorgant S, Lehy T. Glycine-extended gastrin promotes the invasiveness of human colon cancer cells. Biochem Biophys Res Commun. 2001;285:136–141
  66. Prigge ST, Kolhekar AS, Eipper BA, et al. Amidation of bioactive peptides: the structure of peptidylglycine alpha-hydroxylating monooxygenase. Science. 1997;278:1300–1305

PII: S0001-2998(02)80028-9

doi: 10.1053/snuc.2002.31028

Seminars in Nuclear Medicine
Volume 32, Issue 2 , Pages 97-109 , April 2002

Article Tools