Synthesis, purification, and tumor cell uptake of67Ga-deferoxamine-folate, a potential radiopharmaceutical for tumor imaging

Susan Wang, Robert J. Lee, Carla J. Mathias, Mark A. Green, Philip S. Low

Research output: Contribution to journalArticle

216 Scopus citations

Abstract

The vitamin folic acid was covalently linked to the chelating agent deferoxamine (DF) via an amide bond using a simple carbodiimide coupling reaction. A mixture of two isomers, DF - folate(α) and DF - folate(γ), was produced involving the α- and γ-carboxyl group of folic acid, respectively. These two isomers were separated by anion-exchange chromatography using a NH4HCO3 gradient. Competitive binding studies revealed that only the DF-folate(γ) is recognized by the folate receptor on KB cells, interacting with an affinity comparable to unconjugated folic acid. The DF - folate conjugates were radiolabeled with the γ-emitting radionuclide 67Ga3+ and tested for uptake by cultured KB cells overexpressing the folate receptor. The cellular accumulation of 67Ga-DF - folate(γ) complex was found to be time-, temperature-, and concentration-dependent. The 67Ga-DF - folate(γ) tracer exhibited rapid uptake kinetics in cell culture with a t1/2 of ∼3 min. The KB cell association of 67Ga-DF - folat(γ) was competitively blocked by free folic acid, indicating that uptake of the 67Ga-DF -folate(γ) was specifically mediated by the folate receptor. Since the folate receptor is overexpressed on the surfaces of many neoplastic cells, these results suggest that 67Ga-DF - folate(γ) complex might be useful as a diagnostic agent for noninvasive imaging of folate receptor-positing tumors.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalBioconjugate Chemistry
Volume7
Issue number1
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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