Nonpeptidic Z360-Analogs Tagged with Trivalent Radiometals as Anti-CCK2R Cancer Theranostic Agents: A Preclinical Study

Nock et al.

In this study by Nock et al., preclinical SPECT-CT imaging is used to evaluate new anti-CCK2R theranostic agents. Total body SPECT-CT imaging was used as a non-invasive and quantitative screening tool, to select candidates for further clinical evaluation.

Research question

The cholecystokinin subtype 2 receptor (CCK2R) is overexpressed in a variety of human tumors (e.g. thyroid carcinoma, small cell lung cancer, stromal ovarian cancers, gastrointestinal stromal tumors, etc.).The challenge for many anti-CCK2R radioligands is the fast in vivo degradation of peptide based analogs. The goal of the current study is the development of nonpeptidic, antigonist based anti-CCK2R cancer theranostic agents and their preclinical non-invasive evaluation.


SPECT/CT imaging of 3 candidate compounds was done at 4 or 24h post-injection. Six mice bearing twin HEK293-CCK2i4svR and wtHEK293 tumors were injected in the tail vein with a bolus containing [111In]In-GAS1/2/3 (100 μL, 9–12 MBq associated with 3 nmol total injected analog). Normalization of images was performed (i.e., all images having the same color scale range values) to achieve a direct visual comparison between the different groups.


The researchers observed that radioactivity was selectively taken up only by the HEK293-CCK2i4svR tumors, with the receptor-negative tumors remaining devoid of radioactivity for all compounds. These results reveal that tumor uptake of [111In]In-GAS1/2/3 is a CCK2i4svR-mediated process. Furthermore, it was demonstrated that [111In]In-GAS3 displayed a superior pharmacokinetic profile.

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