Purpose: Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in a high percentage of medullary thyroid carcinomas (MTC). Analogous to somatostatin receptors, CCK-2 receptors might be viable targets for radionuclide scintigraphy and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed, and some have been carried through into clinical studies. However, these studies are mostly limited and difficult to compare. The aim of this study was to evaluate the diagnostic and therapeutic potential of three promising CCK-2 receptor-binding radiopeptides in patients with MTC. Methods: 111In-DOTA-(D)Asp-Tyr-Nle-Gly-Trp-Nle- Asp-Phe-NH2 (111In-DOTA-CCK), a CCK analogue, and the gastrin-based ligands 99mTc-N4-Gly-(D)Glu-(Glu) 5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (99mTc- demogastrin 2) and 111In-DOTA-(D)Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe- NH2 (111In-DOTA-MG11) were each administered to the same group of six patients. Planar images made at 3-5, 7 and 24 h p.i. were used for comparison of tumour visualisation and renal uptake. Results: 99mTc-demogastrin 2 scintigraphy visualised all known lesions and new lesions in four of six patients. 111In-DOTA-CCK and 111In-DOTA-MG11 on the other hand missed several lesions; tumour uptake of these two radiopharmaceuticals was quite low. Comparison of retention of renal activity showed no major differences between the three radiopeptides. Conclusion: 99mTc-demogastrin 2 scintigraphy appeared most promising as a diagnostic tool in patients with MTC. Further studies are required to evaluate its value in patient management. Direct comparisons of the compounds studied strongly suggests that 111In-DOTA-CCK and 111In-DOTA-MG11 have less potential as imaging agents than 99mTc-demogastrin 2. These DOTA-linked compounds are considered unlikely to be useful for radionuclide therapy because of low tumour uptake.

1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid cholecystokinin 2 in 111, 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid mg 11 in 111, CCK-2 receptor, Cholecystokinin, Medullary thyroid carcinoma, Minigastrin, adolescent, adult, aged, amino acid sequence, article, brain stem tumor, calcitonin blood level, cancer diagnosis, chemistry, chest tightness, cholecystokinin B receptor, clinical article, comparative study, demograstin 2 tc 99 m, diagnostic agent, diagnostic imaging, diagnostic value, distant metastasis, dizziness, dose kidney function relation, female, flushing, heart rate, high performance liquid chromatography, human, indium, isotope labeling, male, metabolism, middle aged, nausea, oligopeptide, paresthesia, radioactivity, radiopharmaceutical agent, receptor binding, scintiscanning, side effect, spleen, thin layer chromatography, thyroid medullary carcinoma, thyroid scintiscanning, thyroid tumor, tissue distribution, unclassified drug, vomiting
dx.doi.org/10.1007/s00259-009-1098-9, hdl.handle.net/1765/17696
European Journal of Nuclear Medicine and Molecular Imaging
Erasmus MC: University Medical Center Rotterdam

Fröberg, A.C, de Jong, M, Nock, B.A, Breeman, W.A.P, Erion, J.L, Maina, T, … Krenning, E.P. (2009). Comparison of three radiolabelled peptide analogues for CCK-2 receptor scintigraphy in medullary thyroid carcinoma. European Journal of Nuclear Medicine and Molecular Imaging, 36(8), 1265–1272. doi:10.1007/s00259-009-1098-9