[PDF] Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy | Semantic Scholar (2024)

The potential of radiolabeled sdAb 4AH29 as a radiotheranostic agent for FAP-positive cancers, warranting clinical evaluation, is confirmed.

It is concluded that [177Lu]Lu-FAP8-PEG3-IP-DOTA constitutes a promising and safe RPT candidate for FAPα-targeted radionuclide therapy of solid tumors, with minimal or no evidence of systemic toxicity.

In a preclinical model, FAP-targeted radiotherapy enhanced anti-PD-1-mediated TGI by modulating the TME and increasing the recruitment of tumor-infiltrating CD8^+ T cells.

The current (pre)clinical data on FAP TRT is reviewed and its perspective towards broader clinical implementation is discussed and it is hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer.

The superior affinity and faster tumor accumulation of eFAP-6 over FAPI-46 makes it a suitable compound for radionuclide imaging and after further optimization, the eFAP series has great potential for various oncological interventions, including fluorescent-guided surgery and effective targeted radionuclide theranostics.

A 177Lu-labeled anti-FAP antibody, PKU525, is reported as a therapeutic radiopharmaceutical for FAP-targeted radiotherapy and its tumor accumulation is rapid and high with a clean background, showing that it is promising for further clinical translational studies.

Developing [68Ga]Ga-DOTA-FD1 for same-day PET imaging of FAP dynamics and [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 for effective radioligand therapy of FAP-overexpressing tumors.

PNT6555 has potential for clinical translation as a theranostic agent in FAP-positive cancer and in therapeutic studies, all 3 177Lu-DOTA-FAPIs exhibited significant antitumor activity at well-tolerated doses, with 177Lu-PNT6555 producing the greatest tumor growth delay and animal survival.

This study demonstrates the successful synthesis and evaluation of a novel FAPI targeting probe, [68Ga]Ga-DOTA-GPFAPI-04, with a Gly-Pro sequence that shows favorable in vivo glioblastoma imaging properties and relatively long tumor retention, highlighting DOTA- GPF API-04 as a promising molecular scaffold for developing FAP targeting tumor theranostic agents.

This review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides in tumor imaging and therapy and incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

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FAPI-04 represents a promising tracer for both diagnostic imaging and, possibly, targeted therapy of malignant tumors with a high content of activated fibroblasts, such as breast cancer.

Although initial tumor uptake was high and FAPα-specific, RPS-309 also progressively cleared from tumors, and therefore serves as a platform for future structure-activity relationship studies and incorporates multiple sites in which structural diversity can be introduced.

Favorable radiochemical properties, rapid clearance from organs and soft tissues, and intense tumor uptake validate 68Ga-OncoFAP as a powerful alternative to currently available FAP tracers.

The results show the potential of ESC11 and ESC14 as potent radioimmunoconjugates or antibody–drug conjugates for diagnostic and therapeutic use in patients with FAP-expressing tumors.

99mTc-FAPI-34 represents a powerful tracer for diagnostic scintigraphy, especially when PET imaging is not available and the chelator used in this compound allows labeling with the therapeutic nuclide 188Re, which is planned for the near future.

A high potential for the clinical use of 68Ga-FAPI-PET/CT for patients diagnosed with sarcoma is suggested, based on the preliminary findings of this retrospective study.

Development of OncoFAP, an ultra-high-affinity ligand of fibroblast activation protein (FAP) for targeting applications with pan-tumoral potential, and various fluorescent and radiolabeled derivatives of On coFAP are generated in order to study biodistribution properties and tumor-targeting performance in preclinical models are described.

Radiolabeled FAPIs allow fast imaging with very high contrast in tumors having a high stromal content and may therefore serve as pantumor agents.

Two new (4-quinolinoyl)-glycyl-2-cyanopyrrolidine-based small molecules for imaging of FAP, QCP01 and [111In]QCP02, using optical and single-photon computed tomography/CT, respectively, have been synthesized and characterized.

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