Synthesis of [(99m)Tc]DTPA-folate and its evaluation as a folate-receptor-targeted radiopharmaceutical.
A DTPA-folate conjugate was radiolabeled with (99m)Tc by stannous chloride reduction of [(99m)Tc]sodium pertechnetate in an aqueous solution of DTPA-folate. The radiochemical purity of the product consistently exceeded 97%, as assessed by thin-layer chromatography employing conditions analogous to those for radiochemical quality control of the radiopharmaceutical [(99m)Tc]DTPA. HPLC demonstrated that the radiolabeled product resulted from the intact DTPA-folate conjugate and not unconjugated DTPA. The ability of [(99m)Tc]DTPA-folate to target folate receptors in vivo was assessed in biodistribution studies with athymic mice bearing subcutaneous folate-receptor-positive human KB cell tumors. As an internal control, previously studied [(111)In]DTPA-folate was coinjected with the [(99m)Tc]DTPA-folate, along with varying amounts of DTPA-folate (0.38 mg/kg, 1.6 mg/kg, or 14 mg/kg). At each DTPA-folate dose, [(99m)Tc]DTPA-folate exhibited tumor uptake comparable to that of the coadministered [(111)In]DTPA-folate, with radiotracer levels declining at the higher DTPA-folate doses due to competitive receptor binding of the unlabeled conjugate. Tumor uptake of both tracers was also competitively blocked by preadministered folic acid dihydrate (2.9 mg/kg). Tumor-to-background tissue contrast obtained with [(99m)Tc]DTPA-folate was generally similar to that obtained with [(111)In]DTPA-folate. The (99m)Tc-labeled DTPA-folate conjugate may have utility as a targeted radiopharmaceutical for imaging neoplastic tissues known to overexpress the folate receptor.
Mathias
C J
CJ
Department of Medicinal Chemistry and Molecular Pharmacology, 1333 Pharmacy Building, and Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-1333, USA.
Hubers
D
D
Low
P S
PS
Green
M A
MA
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D005069:Evaluation Studies as Topic; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011956:Receptors, Cell Surface; D016284:Technetium Tc 99m Pentetate / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface; D005492:Folic Acid; D016284:Technetium Tc 99m Pentetate