Title:Cholecystokinin-2 Receptor Targeting with Radiolabeled Peptides: Current Status and Future Directions
Volume: 27
Issue: 41
关键词:
胆囊收缩素2受体，分子成像，靶向放射治疗，胃泌素，胆囊收缩素，放射性金属。
摘要: A wide variety of radiolabeled peptide analogs for specific targeting of cholecystokinin-
2 receptors (CCK2R) has been developed in the last decades. Peptide probes based
on the natural ligands Minigastrin (MG) and Cholecystokinin (CCK) have a high potential for
molecular imaging and targeted radiotherapy of different human tumors, such as Medullary
Thyroid Carcinoma (MTC) and Small Cell Lung Cancer (SCLC). MG analogs with high persistent
uptake in CCK2R expressing tumors have been preferably used for the development of
radiolabeled peptide analogs. The clinical translation of CCK2R targeting has been prevented
due to high kidney uptake or low metabolic stability of the different radiopeptides developed.
Great efforts in radiopharmaceutical development have been undertaken to overcome these
limitations. Various modifications in the linear peptide sequence of MG have been introduced
mainly with the aim to reduce kidney retention. Furthermore, improved tumor uptake could be
obtained by in situ stabilization of the radiopeptide against enzymatic degradation through coinjection
of peptidase inhibitors. Recent developments focusing on the stabilization of the Cterminal
receptor binding sequence (Trp-Met-Asp-Phe-NH2) have led to new radiolabeled
MG analogs with highly improved tumor uptake and tumor-to-kidney ratio. In this review, all
the different aspects in the radiopharmaceutical development of CCK2R targeting peptide
probes are covered, giving also an overview on the clinical investigations performed so far.
The recent development of radiolabeled MG analogs, which are highly stabilized against enzymatic
degradation in vivo, promises to have a high impact on the clinical management of
patients with CCK2R expressing tumors in the near future.
