CCKBR (Cholecystokinin B Receptor)

Efficacy studies revealed a reduction in mean tumor volume of up to 65% in two independent orthotopic mouse models, with no tumor evident in some of the animals treated with the CCK2p-boundPAPTP construct. Our data suggest that tumor-specific targeting of small molecules may be a promising strategy for precision medicine against PDAC.

This review summarises clinical evidence, translational advances, and future perspectives for PRRT as a cornerstone of precision nuclear oncology. Emphasis is placed on expanding indications, integrating α-emitters, improving safety and dosimetry, and developing novel theragnostic ligands that enable personalised treatment strategies for NETs patients.

In the first patient with SCLC treated with four cycles of [177Lu]Lu-DOTA-MGS5 with a total activity of 17.2 GBq, an improvement in clinical symptoms was observed. The preclinical and clinical results confirm the feasibility of [177Lu]Lu-DOTA-MGS5 PRRT in patients with SCLC and support further clinical studies investigating the therapeutic value and clinical applicability of this new CCK2R-targeted theranostic approach in larger patient cohorts.

In xenograft studies, 20 MBq doses of gastramide compounds extended median survival by 22-23.5 days versus only 6 days for CP04. These results establish gastramide theranostics as an effective approach to CCK2R-targeted therapy, addressing current limitations and providing an improved treatment option for neuroendocrine tumors with substantially enhanced therapeutic outcomes.

These experiments combine transcriptomic profiling with functional validation to provide a comprehensive analysis of how targeting CCK-BR interrupts the cross-communication between cancer cells and fibroblasts. Blockade or downregulation of the CCK-BR on pancreatic fibroblasts may provide a strategy to disrupt oncogenic signaling pathways and reprogram the tumor microenvironment.

We report a novel role for G-cell-derived gastrin in ulcer healing. Hypogastrinaemia is a risk factor for poor ulcer healing, corpus atrophy and potentially cancer, while physiological gastrin responses are protective. PPI-induced hypergastrinaemia plays a key role in ulcer healing, and gastrin signalling may prevent gastric preneoplasia.

This review offers a comprehensive overview of the current landscape in cancer radiotheranostics, exploring the role of CCK2R in cancer biology and summarizing the latest advancements in the development of CCK2R-targeted radiopharmaceuticals. Using these advancements as a case study, we systematically examine key aspects of next-generation radiopharmaceutical design, from target selection and ligand engineering to pharmacokinetic optimization and clinical translation, providing a multidimensional framework for future innovation in cancer radiotheranostics.

Furthermore, we combined [177Lu]Lu-DOTA-CCK2R-dimer with the mTOR inhibitor RAD001 and used single-cell RNA sequencing (scRNA-seq) to investigate the mechanisms of radiosensitization... DOTA-CCK2R-dimer exhibits favorable in vivo stability, notable tumor retention, and excellent imaging performance. Combining this agent with mTOR inhibition offers a synergistic strategy to sensitize tumors to radiotherapy, providing a promising approach for treating refractory CCK2R-positive malignancies.

In patients with non-MTC NETs, 68Ga-DOTA-MGS5 PET/CT showed possible applicability in patients with BP-NETs, which needs to be verified in a larger patient cohort. In contrast, 68Ga-DOTA-MGS5 PET/CT seemed to be of limited value in patients with GEP-NETs.

In conclusion, c-myc overexpression makes adolescents and young adults breast cancer more aggressive through multifaceted roles including relevantly expressed cholecystokinin B receptor. Clinical trial registration: This study is not a clinical trial.

The INER-PP-F11N radiopharmaceutical was superior as a theragnostic agent compared with the current PP-F11N. Our study suggests that INER-PP-F11N may be an innovative radiopharmaceutical agent for CCK2R-overexpressing tumors.

Procalcitonin concentrations after CP04 stimulation were highly correlated with calcitonin concentrations. Unlabeled CP04, if available commercially, may be considered an alternative stimulating agent in MTC patients, even in lower mass amounts. Further studies, including healthy controls, are required to prove this concept and calculate the diagnostic thresholds.