Targeting the folate receptor (FR): Imaging and cytotoxicity of Re I conjugates in FR-overexpressing cancer cells

Nerissa Viola-Villegas, Amy E. Rabideau, Justin Cesnavicious, Jon Zubieta, Robert P. Doyle

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


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 IC50 values of 189 and 78 μM at 6 and 24 h, respectively, toward the FR-positive cell line. This is in contrast to the IC50 value of 502 μM at 6 h and 84 mu;M 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.

Original languageEnglish (US)
Pages (from-to)1387-1394
Number of pages8
Issue number9
StatePublished - Sep 15 2008


  • Confocal microscopy
  • Cytotoxicity
  • DNA
  • Folate
  • Rhenium

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry


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