Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of Re~I Conjugates in FR-Overexpressing Cancer Cells

摘要

The synthesis, characterization, in vitro imaging, and cytotoxic properties of a new folate conjugate of rhenium(I) are leporled. The conjugate [FA-PEG-BQAV-Re(CO)3]~+ (γ-4) was screened against an adriamycin- and cisplolin-resistant human ovarian cancel cell line (A2780/AD) that overexpresses the folate receptor (FR). Compound γ-4 was internalized by a folate-receptor-medi-ated endocytotic pathway, which results in internal accumulation of γ-4. This was contrasted with a FR-negative Chinese hamster ovary cell line in which no internalization of γ-4 was observed. γ-4 was found to be cytotoxic with IC_(50) values of 189 and 78 μм at 6 and 24 h, respectively, loward the FR-positive cell line. This is in contrast to the IC_(50) value of 502 μм or 6h and 84 μм at 24 h for cisplatin in the same cell line, with a significantly greater tox-icity at the earlier lime point. The cytotoxicity of γ-4 as explained by interactions that occur between the rhenium(I) complex moiety and DNA is described.