CCKBR expression

As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.

Proglumide is an older drug that is orally bioavailable and being repurposed for liver conditions. These findings support a promising therapeutic intervention applicable to patients to prevent the development of HCC and decrease hepatic fibrosis.

Nevertheless, dermal fibroblasts/myofibroblasts, known also to express CCK2R, increased gastrin-induced cancer cell invasion. Our data suggest that in a subset of melanoma patients, an elevated serum gastrin concentration is a risk factor for melanoma tumor progression, and that gastrin may act on both melanoma and adjacent stromal cells through CCK2 receptors to promote mechanisms of tumor migration and invasion.

In 2018, the FDA approved Lutathera for the first-in-class peptide receptor radionuclide therapy of gastroenteropancreatic and neuroendocrine tumors. More recently, Pluvicto was approved for the treatment of metastatic prostate cancers...In vivo, pharmacological inhibition of mTORC1 by RAD001 or 5HT3R by ondansetron significantly enhanced uptake of [177Lu]Lu-PP-F11N selectively in tumors without altering uptake in healthy organs such as the kidney or stomach. Furthermore, RAD001 enhanced the therapeutic efficacy of [177Lu]Lu-PP-F11N in CCKBR-tumor-bearing mice without adverse effects suggesting further development of the combinatory treatment for clinical applications.ConclusionOur study established a screen-based workflow suitable for identifying molecular targets for enhanced uptake or radiolabeled ligands. The follow-up study demonstrates the potential of mTORC1 inhibitor RAD001 to substantially increase tumor uptake and therapeutic efficacy of radiolabeled minigastrin in CCKBR-positive cancers, feasible for clinical development.