FAP-2286 is a potent and selective FAP-binding peptide conjugated to a radionuclide chelator with a mean IC50 value of 2.7 ± 0.9nM for inhibiting human FAP protease activity. Fibroblast activation protein (FAP) is a membrane-bound protease highly expressed on cancer-associated fibroblasts (CAFs) and some tumor cells, with limited expression in normal adult tissues. The high binding affinity FAP-2286 enables the attachment of radionuclides for imaging and therapeutic use in oncology[1][2].
In vitro, [13xLa]La-FAP-2286 (1-100nM) incubated HEK-FAP+ and CHO FAP- cells confirming the strong affinity of the radiolabeled complex to the FAPI-expressing human cell line[3].
In vivo, 177Lu-FAP-2286 (30 or 60MBq/nmol) was administrated into HEK-FAP xenograft mouse model via Intravenous injection. Signifcant antitumor activity was observed with tumor growth inhibition (TGI) of 111% and 113% respectively on day 14[1]. [13xLa]La-FAP-2286 (200µL, 7.4MBq) were intravenously (i.v.) injected into both normal and HEK FAP+ tumor-bearing mice through their tail vein. The biodistribution of [13xLa]La-FAP-2286 in tumor-bearing mice showed the significant accumulation of the radiolabeled compound in tumors and kidney[3]. FAP-2286-modified LNP-based nano vector (20mg/kg) was administered via intravenous injection in subcutaneous RM-1 tumor model. Tumor accumulation was significantly increased at each time point (3, 6, 9, 12, and 24 hours after injection), with 2.1-fold, 3.2-fold, 9.2-fold, and 10.5-fold increases, respectively camparing to unmodified LNP[4].
References:
[1] Zboralski D, Hoehne A, Bredenbeck A, et al. Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. Eur J Nucl Med Mol Imaging. 2022 Sep;49(11):3651-3667.
[2] Pang Y C, Zhao L, Meng T H, et al. PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using 68Ga-FAP-2286: Comparison with 18F-FDG and 68Ga-FAPI-46 in a Single-Center, Prospective Study. J Nucl Med. 2023 Mar;64(3):386-394.
[3] Shirpour A, Hadadi A, Zolghadri S,et al. Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein. Sci Rep. 2025 Mar 3;15(1):7475.
[4] Qi F, Fu D, Cai H Z, et al. Metabolic Reprogramming of Cancer-Associated Fibroblasts: Transforming Tumor Accomplices into Immunotherapeutic Allies. Adv. Funct. Mater. 2024, 2418240