99ᵐTc-DTPA-OM: Cardiac-myosin targeted SPECT agent for non-invasive myocardial infarction imaging.

Effective molecular imaging of myocardial infarction (MI) requires small, selective agents that can access damaged tissue and bind to intracellular biomarkers exposed during necrosis. Here, we report the development of 99mTc-DTPA-OM, a novel small-molecule radiotracer designed for the noninvasive imaging of Myocardial Infarction (MI). The tracer was synthesized by conjugating the DTPA chelator to a cardiac myosin activator analog, OM. Initial in vitro functional assays confirmed that this modification did not compromise the molecule's intrinsic mechanism of action, retaining its ability to induce a positive inotropic effect via direct sarcomere activation. Optimization of the radiolabeling procedure yielded 99mTc-DTPA-OM, with high radiochemical purity. Functional verification confirmed that the radiolabeling process did not impair molecular targeting, with substantial 99mTc-DTPA-OM activity bound to cardiac myosin. The tracer demonstrated excellent stability under physiological conditions and hemocompatibility. The diagnostic capability was evaluated in a surgical mouse MI model. Planar and SPECT imaging at 1 h post-injection revealed significant radiotracer uptake specifically in the MI mouse. Biodistribution confirmed this specificity, showing elevated heart uptake in MI mice coupled with reduced non-specific uptake in clearance organs (liver, kidney, stomach). Finally, a strong correlation was established between the SPECT uptake area and the region of myocardial necrosis confirmed by TTC staining of harvested hearts. These findings establish 99mTc-DTPA-OM as a promising targeted imaging agent for MI diagnosis and therapeutic monitoring.