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

Authors :
Ayaka Aso
Hinako Nabetani
Yoshifumi Matsuura
Yuichiro Kadonaga
Yoshifumi Shirakami
Tadashi Watabe
Taku Yoshiya
Masayoshi Mochizuki
Kazuhiro Ooe
Atsuko Kawakami
Naoya Jinno
Atsushi Toyoshima
Hiromitsu Haba
Yang Wang
Jens Cardinale
Frederik Lars Giesel
Atsushi Shimoyama
Kazuko Kaneda-Nakashima
Koichi Fukase
Source :
International Journal of Molecular Sciences; Volume 24; Issue 10; Pages: 8701
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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 211At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and 211At-attaching moieties. 211At-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, 211At was superior to 131I 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.

Details

ISSN :
14220067
Volume :
24
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....fce9c06fd84ec23e7586a7e051493d00