Preparation and Evaluation of ⁹⁹Tc^m-HL91 Derivatives for Tumor Hypoxia Imaging

In order to find the optimum hypoxia imaging agent, two derivatives of HL91－4, 9-diaza-3, 10-dimethyl-dodecane-2, 11-dione dioxime (TMBAO) and N, N’-bis (2-hydroxyimino propionyl)-1, 4-diaminobutane(H₂Pab)—were synthesized and labeled with ⁹⁹Tc^m. Evaluation of these complexes as tumor hypoxia markers were performed both in vitroand in vivocompared with ⁹⁹Tc^m-HL91—a putative hypoxic tracer. The tumor cell experiment and the biodistribution in mice bearing EMT-6 tumor show that the two derivatives—⁹⁹Tc^m-TMBAO and ⁹⁹Tc^m-H₂Pab have less hypoxic selectivity than ⁹⁹Tc^m-HL91 in despite of their lower liver uptake.