Synthesis and biological evaluation of (99m)Tc-DTPA-bis(His) as a potential probe for tumor imaging with SPECT.

(99m)Tc-DTPA-bis(His) conjugate has been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compound was synthesized by the covalent coupling of DTPA bis(anhydride) with L-histidine and was characterized on the basis of infrared, nuclear magnetic resonance, and mass spectroscopy. (99m)Tc-labeled compound was found stable for about 24 hour under physiologic conditions with a more than 96% radiolabeling yield. A blood kinetic study of this complex showed a biexponential pattern as well as quick washout from the blood circulation. The biologic t(1/2)(F) and t(1/2)(S) was found to be 45 +/- 0.041 minutes and 6.5 hours +/- 0.039 minutes, respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in the right thigh. The EAT tumors in the mice were readily visible in the gamma-images and showed major accumulation of the radiotracer in the kidney. Biodistribution studies revealed a high accumulation at the tumor site. Tumor-to-muscle ratios were 5.07 +/- 0.08 and 4.2 +/- 0.01 at 1 and 4 hours, respectively. The receptor binding of the (99m)Tc-DTPA-bis(His) by an established human tumor cell line (U87-MG) showed K(D) = 1.08 nM. The preliminary studies of the (99m)Tc-DTPA-bis(His) are encouraging to carrying out further in vivo experiments for targeted tumor imaging.