RRC ID 78714
Author Aso A, Nabetani H, Matsuura Y, Kadonaga Y, Shirakami Y, Watabe T, Yoshiya T, Mochizuki M, Ooe K, Kawakami A, Jinno N, Toyoshima A, Haba H, Wang Y, Cardinale J, Giesel FL, Shimoyama A, Kaneda-Nakashima K, Fukase K.
Title Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.
Journal Int J Mol Sci
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.
Volume 24(10)
Published 2023-5-12
DOI 10.3390/ijms24108701
PII ijms24108701
PMID 37240044
PMC PMC10218645
MeSH Animals Fibroblasts* Gallium Radioisotopes HEK293 Cells Humans Mice Piperazine / pharmacology Polyethylene Glycols* / pharmacology Positron Emission Tomography Computed Tomography
Human and Animal Cells 293(RCB1637) A549