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CURRENT ISSUETHE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING

A Journal on Nuclear Medicine and Molecular Imaging


A Journal on Nuclear Medicine and Molecular Imaging
Affiliated to the Society of Radiopharmaceutical Sciences and to the International Research Group of Immunoscintigraphy
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index (SciSearch), Scopus
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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2015 September;59(3):287-302

RADIOPHARMACOLOGY - RECENT DEVELOPMENTS IN THE FIELD OF RADIOPHARMACEUTICALS 

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Radiolabeled gastrin/CCK analogs in tumor diagnosis: towards higher stability and improved tumor targeting

Kaloudi A. 1, Nock B. A. 1, Krenning E. P. 2, Maina T. 1, De Jong M. 2, 3

1 Molecular Radiopharmacy, INRASTES National Center for Scientific Research, “Demokritos”, Athens, Greece;
2 Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands;
3 Department of Radiology, Erasmus MC, Rotterdam, The Netherlands

Cholecystokinin subtype 2 receptors (CCK2R) are overexpressed in several human cancers, including medullary thyroid carcinoma. Gastrin and cholecystokinin (CCK) peptides that bind with high affinity and specificity to CCK2R can be used as carriers of radioactivity to CCK2R-expressing tumor sites. Several gastrin and CCK related peptides have been proposed for diagnostic imaging and radionuclide therapy of primary and metastatic CCK2R-positive human tumors. Their clinical application has been restricted to a great extent by their fast in vivo degradation that eventually compromises tumor uptake. This problem has been addressed by structural modifications of gastrin and CCK motifs, which, however, often lead to suboptimal pharmacokinetic profiles. A major enzyme implicated in the catabolism of gastrin and CCK based peptides is neutral endopeptidase (NEP), which is widely distributed in the body. Coinjection of the NEP inhibitor phosphoramidon (PA) with radiolabeled gastrin and other peptide analogs has been recently proposed as a new promising strategy to increase bioavailability and tumor-localization of radiopeptides in tumor sites. Specifically, co-administration of PA with the truncated gastrin analog [111In-DOTA]MG11 ([(111In-DOTA)DGlu10]gastrin(10-17)) impressively enhanced the levels of intact radiopeptide in mouse circulation and has led to an 8-fold increase of CCK2R-positive tumor uptake in SCID mice. This increased tumor uptake, visualized also by SPECT/CT imaging, is expected to eventually translate into higher diagnostic sensitivity and improved therapeutic efficacy of radiolabeled gastrin analogs in CCK2R-expressing cancer patients.

language: English


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