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

✍ Scribed by Nerissa Viola-Villegas; Amy E. Rabideau; Justin Cesnavicious; Jon Zubieta; Robert P. Doyle

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 360 KB
• Volume: 3
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.200800125

✦ Synopsis

Abstract

The synthesis, characterization, in vitro imaging, and cytotoxic properties of a new folate conjugate of rhenium(I) are reported. The conjugate [FA‐PEG‐BQAV‐Re(CO)~3~]^+^ (γ‐4) was screened against an adriamycin‐ and cisplatin‐resistant human ovarian cancer cell line (A2780/AD) that overexpresses the folate receptor (FR). Compound γ‐4 was internalized by a folate‐receptor‐mediated 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 μM at 6 and 24 h, respectively, toward the FR‐positive cell line. This is in contrast to the IC~50~ value of 502 μM at 6 h and 84 μM at 24 h for cisplatin in the same cell line, with a significantly greater toxicity at the earlier time point. The cytotoxicity of γ‐4 as explained by interactions that occur between the rhenium(I) complex moiety and DNA is described.