Synthesis, purification, and tumor cell uptake of 67Ga-deferoxamine--folate, a potential radiopharmaceutical for tumor imaging

Bioconjug Chem. 1996 Jan-Feb;7(1):56-62. doi: 10.1021/bc9500709.


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(alpha) and DF--folate(gamma), was produced involving the alpha- and gamma-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(gamma) 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 gamma-emitting radionuclide 67Ga3+ and tested for uptake by cultured KB cells overexpressing the folate receptor. The cellular accumulation of 67Ga-DF-folate(gamma) tracer exhibited rapid uptake kinetics in cell culture with a t1/2 of approximately 3 min. The KB cell association of 67Ga-DF--folate(gamma) was competitively blocked by free folic acid, indicating that uptake of the 67Ga-DF--folate(gamma) 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(gamma) complex might be useful as a diagnostic agent for noninvasive imaging of folate receptor-positing tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Carrier Proteins / metabolism
  • Cell Line
  • Chromatography, Ion Exchange
  • Deferoxamine* / analogs & derivatives*
  • Deferoxamine* / chemical synthesis
  • Deferoxamine* / isolation & purification
  • Deferoxamine* / metabolism
  • Folate Receptors, GPI-Anchored
  • Folic Acid* / analogs & derivatives*
  • Folic Acid* / chemical synthesis
  • Folic Acid* / isolation & purification
  • Folic Acid* / metabolism
  • Gallium Radioisotopes*
  • Humans
  • KB Cells
  • Kinetics
  • Lung
  • Neoplasms / diagnostic imaging
  • Radioimmunodetection
  • Receptors, Cell Surface*
  • Spectrometry, Mass, Fast Atom Bombardment


  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Gallium Radioisotopes
  • Receptors, Cell Surface
  • deferoxamine-gamma-folate conjugate
  • Folic Acid
  • Deferoxamine