Preparation of Hypoxic Imaging Agents ⁹⁹Tc^m-MNLS and ⁹⁹Tc^m-MLS and Their Biodistribution in Mice

To develop ⁹⁹Tc^m labeled hypoxic agents, two phosphate-based chelating agents were coupled to metronidazole, 2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MNLS) and its analog 2-（2-methyl-1H-imidazol-1-yl）ethyl dihydrogen phosphate（MLS）were synthesized based on the mechanism of prodrug. Labeling yield of these ⁹⁹Tc^m complexes were more than 90% as proved by TLC. Paper electrophoresis showed that these complexes were neutral. Biodistribution of these complexes in tumor-bearing mice showed that the uptake of ⁹⁹Tc^m-MNLS (120 min, 2.99±0.25 ID%/g) in tumor was higher than that of ⁹⁹Tc^m-HL91(120 min, 0.93±0.13 ID%/g) and ⁹⁹Tc^m-MLS(120 min, 1.61±0.13 ID%/g), and the uptake ratio of tumor to muscle and tumor to liver of ⁹⁹Tc^m-MNLS (120 min, 5.90， 1.03) were higher than that of ⁹⁹Tc^m-HL91(120 min, 3.59， 017) and ⁹⁹Tc^m-MLS(120 min, 5.40， 0.13）. The higher tumor uptake for ⁹⁹Tc^m-MNLS than ⁹⁹Tc^m-MLS suggested that nitroimidazole was a key group for tumor accumulation. ⁹⁹Tc^m-MNLS had higher tumor uptake and lower liver uptake, which had the potential for tumor imaging and was worth of further vestigation.