Tc-99m-HYNIC-folate: A novel receptor-based targeted radiopharmaceutical for tumor imaging

The folate receptor is overexpressed in a wide variety of human tumors. Con jugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In this study, a novel radiopharmaceutical, Tc-99 m-6-hydrazinonicotinamido-hydrazido (HYNIC)-folate, was synthesized and eva luated for its efficacy as a targeted agent for the imaging of tumors that overexpress the folate receptor. Methods: HYNIC-folate was synthesized and radiolabeled with Tc-99m using tricine and trisodium triphenylphosphine-3,3 ',3 "-trisulfonate as coligands. The receptor binding properties of Tc-99m- HYNIC-folate were studied in cultured tumor cells that overexpress the fola te receptor. The tumor-localizing properties of 99mTc-HYNIC-folate were the n evaluated in C57BL/6 mice bearing subcutaneously implanted folate recepto r-positive syngeneic tumors. Tissue distribution was determined at two diff erent time points, and gamma camera images were collected on two animals. R esults: The folate receptor-mediated uptake of Tc-99m-HYNIC-folate by cultu red tumor cells was approximately 300 times higher than the nonspecific bin ding determined in the presence of 1 mmol/L free folic acid. Excellent tumo r selectivity was also shown in the animal model; tumor-to-blood ratios rea ched 55 +/- 19 and 81 +/- 6 at 4 and 24 h after injection, respectively. Tu mor uptake of the radiotracer was blocked by the co-injection of 100 mu g f ree folate. Tumors were clearly identifiable on the gamma camera images, wi th the kidneys and the bladder as the only normal organs showing high level s of the radiotracer. Conclusion: Tc-99m-HYNIC-folate is a promising, novel receptor-specific radiopharmaceutical with potential applications in the i maging of human tumors.