Synthesis of [99mTc]DTPA-Folate and Its Evaluation as a Folate-Receptor-Targeted Radiopharmaceutical

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Abstract
A DTPA−folate conjugate was radiolabeled with 99mTc by stannous chloride reduction of [99mTc]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 [99mTc]DTPA. HPLC demonstrated that the radiolabeled product resulted from the intact DTPA−folate conjugate and not unconjugated DTPA. The ability of [99mTc]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 [111In]DTPA−folate was coinjected with the [99mTc]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, [99mTc]DTPA−folate exhibited tumor uptake comparable to that of the coadministered [111In]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 [99mTc]DTPA−folate was generally similar to that obtained with [111In]DTPA−folate. The 99mTc-labeled DTPA−folate conjugate may have utility as a targeted radiopharmaceutical for imaging neoplastic tissues known to overexpress the folate receptor.