FAP (Fibroblast activation protein, alpha)

RIH is a novel animal model that suggests there can be significant water retention after only a few hours of hyponatremia a day provided this situation is repeated over time. Such water retention translates into a greater brain water accumulation and astroglial activation in the GM.

Nearly half of the patients demonstrated disease stabilization, almost exclusively in sarcomas. Our findings support the role of FAP-directed radiopharmaceutical therapy in patients with metastatic sarcoma.

Further prospective studies are needed to evaluate and establish the role of 18F‑FDG and FAPI-PET in personalized treatment strategies and sarcoma management.

A therapy experiment in immunocompetent mice bearing low FAP-expressing tumors showed that the combination with L19-hIL2 potentiated the antitumoral activity of 177Lu-OncoFAP-23 and OncoFAP-GlyPro-MMAE. These results provided the motivation for the clinical development of these combinations for treating FAP-positive solid tumors.

Importantly, rhDCN-related normalization of active CAFs features was persistent through cellular passaging, and was not accompanied by cytotoxicity. Together, these findings have revealed rhDCN as a promising anti-breast cancer therapeutic cytokine through suppression of the non-cell-autonomous cancer-promoting effects of active CAFs.

MFAP-5 expression in human HCC samples and conserved signaling pathways between mice and humans underscore the translational relevance of this target. Our findings highlight the therapeutic potential of CAF-targeted siRNA delivery using polycarbonate-based nanogels to inhibit stromal-driven angiogenesis and tumor progression in HCC.

Treatment achieved ~62% tumor growth inhibition, prolonged survival beyond 28 days, and induced partial (50%) or complete (17%) responses without systemic toxicity. These findings highlight Macropa as a robust chelation strategy and support Sibrotuzumab-based α-immunoconjugates for precise targeting of FAP-positive desmoplastic tumors.

This review summarizes the biology of FAP expression in the nephro-urological tract and synthesizes emerging evidence on oncological and non-oncological applications of FAP-targeted PET, with a focus on refining lesion characterization, guiding personalised management, and identifying novel theranostic opportunities in nephro-urology. Taken together, current evidence suggests that FAP-targeted PET may become a valuable complement to existing imaging strategies in nephro-urology, although its standalone clinical utility remains uncertain and requires confirmation in larger, prospective, disease-specific studies before routine adoption.

[18F] AlF-NOTA-FAPI-04 PET/CT uptake variables reflected the expression of CAF-related biomarkers. Higher baseline SUVmean on [18F] AlF-NOTA-FAPI-04 PET/CT scans was associated with poor response to nCRT for LARC.

hmFAP2 markedly enhances FAP-targeting efficiency, providing higher binding affinity, improved tumor uptake, and reduced nonspecific distribution compared with its monomeric counterpart. The favorable imaging properties of hmFAP2 position it as a promising candidate for translation into clinical PET imaging and as a potential scaffold for developing FAP-targeted theranostic agents.

18F-NOTA-R49 demonstrates high affinity and specificity and excellent tumor-targeting properties. It shows better diagnostic efficacy than 18F-FDG in various malignant tumors, indicating a significant clinical translation potential.

Additionally, FAPα+ macrophages accelerated T cell senescence by secreting soluble FAPα. Collectively, our findings demonstrate that FAPα+ macrophages mediate MM immune evasion via dual mechanisms, positioning them as promising therapeutic targets to potentiate anti-tumor immunotherapies.