CCK receptors in human neuroendocrine tumors: clinical implications

Abstract

Receptors for gastrin and cholecystokinin have been shown to be expressed in several types of human cancers. CCK-B receptors for instance have been identified in several types of neuroendocrine tumors. One of the highest incidences of CCK-B receptors has been reported in medullary thyroid cancers at the protein and at the mRNA level using in vitro receptor autoradiography and RT-PCR. It is likely that these receptors mediate the stimulation of calcitonin secretion from neoplastic C-cells by pentagastrin, a well established clinical test to detect occult medullary thyroid cancers. In order to target these tumors in vivo in patients, several peptide radiopharmaceuticals such as DTPA-linked minigastrins or non-sulfated CCK-8 analogs radiolabeled with 111Indium or 90Yttrium have recently been developed. As a proof of concept, it could be demonstrated that a majority of medullary thyroid cancer primary tumors and metastases are visualized in vivo with CCK-B receptor scintigraphy using these radioligands. More recently, radiotherapy of CCK-B receptor expressing medullary thyroid cancers with radiolabeled minigastrin has been successfully reported in a small number of patients, giving support to the proposal that CCK-B receptors overexpressed in tumors represent a useful target for clinical application.