S. Wang et al., SYNTHESIS, PURIFICATION, AND TUMOR-CELL UPTAKE OF GA-67-DEFEROXAMINE-FOLATE, A POTENTIAL RADIOPHARMACEUTICAL FOR TUMOR IMAGING, Bioconjugate chemistry, 7(1), 1996, pp. 56-62
The vitamin folic acid was covalently linked to the chelating agent de
feroxamine (DF) via an amide bond using a simple carbodiimide coupling
reaction. A mixture of two isomers, DF-folate(a) 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 re
ceptor on KB cells, interacting with an affinity comparable to unconju
gated folic acid. The DF-folate conjugates were radiolabeled with the
gamma-emitting radionuclide Ga-67(3+) and tested for uptake by culture
d KB cells overexpressing the folate receptor. The cellular accumulati
on of Ga-67-DF-folate(gamma) complex was found to be time-, temperatur
e-, and concentration-dependent. The Ga-67-DF-folate(gamma) tracer exh
ibited rapid uptake kinetics in cell culture with a t(1/2) of similar
to 3 min. The KB cell association of (GaDF)-Ga-67-folate(gamma) was co
mpetitively blocked by free folic acid, indicating that uptake of the
Ga-67-DF-folate(gamma) was specifically mediated by the folate recepto
r. Since the folate receptor is overexpressed on the surfaces of many
neoplastic cells, these results suggest that Ga-67-DF-folate(gamma) co
mplex might be useful as a diagnostic agent for noninvasive imaging of
folate receptor-positing tumors.