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

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

Research output: Contribution to journalArticle

210 Citations (Scopus)

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
StatePublished - 1996
Externally publishedYes

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Deferoxamine
Radiopharmaceuticals
Folic Acid
Purification
Tumors
Cells
Imaging techniques
Acids
Isomers
Neoplasms
Vitamins
Chelation
Chromatography
Amides
Cell culture
Radioisotopes
KB Cells
Ion exchange
Negative ions
Association reactions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Clinical Biochemistry
  • Chemistry(all)
  • Organic Chemistry

Cite this

Synthesis, purification, and tumor cell uptake of67Ga-deferoxamine-folate, a potential radiopharmaceutical for tumor imaging. / Wang, Susan; Lee, Robert J.; Mathias, Carla J.; Green, Mark; Low, Philip S.

In: Bioconjugate Chemistry, Vol. 7, No. 1, 1996, p. 56-62.

Research output: Contribution to journalArticle

Wang, Susan ; Lee, Robert J. ; Mathias, Carla J. ; Green, Mark ; Low, Philip S. / Synthesis, purification, and tumor cell uptake of67Ga-deferoxamine-folate, a potential radiopharmaceutical for tumor imaging. In: Bioconjugate Chemistry. 1996 ; Vol. 7, No. 1. pp. 56-62.
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