CCK receptors in human neuroendocrine tumors: clinical implications

Area of Science:

• Oncology
• Nuclear Medicine
• Endocrinology

Background:

• Gastrin and cholecystokinin receptors are implicated in various human cancers.
• Cholecystokinin-B (CCK-B) receptors are notably found in neuroendocrine tumors, with high incidence in medullary thyroid cancers (MTCs).
• These receptors likely mediate pentagastrin stimulation of calcitonin secretion in MTCs, a phenomenon used in clinical diagnosis.

Purpose of the Study:

• To investigate the potential of CCK-B receptors as a therapeutic and diagnostic target in medullary thyroid cancers.
• To evaluate the efficacy of novel peptide radiopharmaceuticals for in vivo imaging and radiotherapy of CCK-B receptor-expressing MTCs.

Main Methods:

• In vitro receptor autoradiography and RT-PCR to confirm CCK-B receptor expression in MTCs.
• Development and application of peptide radiopharmaceuticals (e.g., DTPA-linked minigastrins, CCK-8 analogs) labeled with 111Indium or 90Yttrium for in vivo scintigraphy.
• Clinical trials assessing radiotherapy using radiolabeled minigastrin in MTC patients.

Main Results:

• High expression of CCK-B receptors confirmed at both protein and mRNA levels in medullary thyroid cancers.
• Successful in vivo visualization of MTC primary tumors and metastases using CCK-B receptor scintigraphy with developed radioligands.
• Positive outcomes reported in a small cohort of patients treated with radiotherapy targeting CCK-B receptors.

Conclusions:

• CCK-B receptors represent a significant and overexpressed target in medullary thyroid cancers.
• Peptide radiopharmaceuticals targeting CCK-B receptors are effective for in vivo diagnosis (scintigraphy) of MTC.
• Radiotherapy utilizing radiolabeled minigastrin demonstrates therapeutic potential for CCK-B receptor-positive MTCs, supporting clinical application.