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
FAP-2286是一种强效且选择性的FAP结合肽，与放射性核素螯合剂相连，抑制人FAP蛋白酶活性的平均IC50值为2.7 ± 0.9nM。成纤维细胞激活蛋白（FAP）是一种膜结合蛋白酶，在癌症相关成纤维细胞（CAFs）和某些肿瘤细胞上高表达，而在正常成人组织中表达有限。FAP-2286的高结合亲和力使其能够连接放射性核素，用于肿瘤学中的成像和治疗应用[1][2]。
在体外实验中，[13xLa]La-FAP-2286（1-100nM）与HEK-FAP+和CHO FAP-细胞孵育，证实了放射性标记复合物对表达FAP的细胞系具有强大的亲和力[3]。
在体内实验中，将177Lu-FAP-2286（30或60MBq/nmol）腹腔注射到HEK-FAP异种移植小鼠模型中。抗肿瘤活性显著，第14天肿瘤生长抑制（TGI）分别为111%和113%[1]。[13xLa]La-FAP-2286（200µL，7.4MBq）通过尾静脉静脉注射进入正常小鼠和HEK FAP+肿瘤荷载小鼠体内。在荷瘤小鼠中，FAP-2286的生物分布显示出放射性标记化合物在肿瘤和肾脏中的显著积累[3]。FAP-2286修饰的基于LNP的纳米载体（20mg/kg）通过静脉注射给药至皮下RM-1肿瘤模型。在注射后3、6、9、12和24h的每个时间点，肿瘤积累显著增加，分别比未修饰的LNP增加了2.1倍、3.2倍、9.2倍和10.5倍[4].