Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

• Published in: International journal of molecular sciences Vol. 24; no. 10; p. 8701
• Main Authors: Aso, Ayaka, Nabetani, Hinako, Matsuura, Yoshifumi, Kadonaga, Yuichiro, Shirakami, Yoshifumi, Watabe, Tadashi, Yoshiya, Taku, Mochizuki, Masayoshi, Ooe, Kazuhiro, Kawakami, Atsuko, Jinno, Naoya, Toyoshima, Atsushi, Haba, Hiromitsu, Wang, Yang, Cardinale, Jens, Giesel, Frederik Lars, Shimoyama, Atsushi, Kaneda-Nakashima, Kazuko, Fukase, Koichi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.05.2023; MDPI
• Subjects: Animals; Antitumor activity; Astatine; astatine-211; Cancer; Care and treatment; Comparative analysis; FAP alpha; Feces; Fibroblast activation protein; Fibroblasts; Gallium Radioisotopes; HEK293 Cells; Humans; Inhibitors; Iodine; iodine-131; Labeling; Lung cancer; Medical research; Mice; Nuclear medicine; Nuclides; PEG-linker; Piperazine; Piperazine - pharmacology; piperazine-linker; Polyethylene glycol; Polyethylene Glycols - pharmacology; Positron Emission Tomography Computed Tomography; Prevention; Proteins; Radiation therapy; Radioisotopes; Stroma; theranostics; Thyroid gland; Tomography; Tumors; Urination; Urine; Japan; astatine-211; PEG-linker; piperazine-linker; FAP alpha; theranostics; cancer; iodine-131
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24108701

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and At-attaching moieties. At-FAPI(s) and piperazine (PIP) linker FAPI exhibited distinct FAP selectivity and uptake in FAPII-overexpressing HEK293 cells and the lung cancer cell line A549. The complexity of the PEG linker did not significantly affect selectivity. The efficiencies of both linkers were almost the same. Comparing the two nuclides, At was superior to I in tumor accumulation. In the mouse model, the antitumor effects of the PEG and PIP linkers were almost the same. Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.