Synthesis of 99m Tc-DOTMP and Its Preclinical Evaluation as a Multidentate Imaging Agent for Skeletal Metastases

Abstract

The convenient synthetic methodology and in vivo stability of the bone-seeking γ-radiation-emitting compound, ^99mTc-DOTMP are described in this paper. The radiolabeling efficiency was found to be >97%, and the stability in serum indicated that ^99mTc remained bound to the chelate, DOTMP, for up to 24 hours. Blood clearance showed a quick washout from the circulation, and biologic half-life was found to be t_1/2(F) = 25 min; t_1/2(S) = 6 hours 5 minutes. The LD₅₀ was found to be 70 mg/kg, as determined by toxicity studies in BALB/c mice. Biodistribution characteristics of ^99mTc-DOTMP were examined in BALB/c mice. The drug was excreted mainly through renal routes and the accumulation of ^99mTc-DOTMP in bone was 9.06 ± 0.75 percent injected dose per gram at 1 hour. Visual image analysis of ^99mTc-DOTMP was clinically comparable to the interpretation of imaging studies with conventional ^99mTc-MDP and other phosphonate derivatives. ^99mTc-DOTMP injected into Balb/c mice showed prominent bone localization and rapid clearance from blood and other organs, thereby making it a promising candidate as a diagnostic pharmaceutical of bone metastases.