Synthesis of M₄IDP and optimum labeling conditions of ⁹⁹Tc^m-M₄IDP

1-Hydroxy-2-(4-methyl-¹H-imidazoleyl)-ethylidene-1, 1-bisphosphonic (M₄IDP) was prepared by three steps of N-alkylation, ester hydrolation and phosphoric acid acylation from the raw material 4-methyl-¹H-imidazole. The structures of intermediate and target compounds were identified by Elemental Analysis, IR, MS and ¹H NMR. Then M₄IDP was directly labeled by Na ⁹⁹Tc^m O₄ to afford ⁹⁹Tc^m-M₄IDP. The results showed that the best labeling conditions were 30 minutes reaction time, pH 6, 100 μg SnCl₂ · 2H₂O, and 5 mg M₄IDP. In this condition, the labeling yield was more than 95% and ⁹⁹Tc^m-M₄IDP showed good biological stability in vitro. (authors)