Development of a 68Ga-based tracer for myocardial imaging

Coronary heart disease (CHD), with its chronic progression, is the most common cause of death in industrialized nations. The myocardial perfusion imaging (MPI) is an important non-invasive method for the diagnosis of CHD. Hence, SPECT tracers like 99mTc-sestamibi, 99mTc-tetrofosmin and PET tracers like [82Rb]RbCl, [13N]NH3 and [15O]H2O are routinely used for heart perfusion and myocard cell damage imaging. To perform PET studies for patients, independent from an on-site cyclotron, it would be desirable to develop a myocardial tracer with a generator-produced nuclide. Due to its favorable nuclide properties and its high availability 68Ga is an ideal candidate for such a project.

Thus, we follow two paths for the development of such a heart tracer in our group:

Mitochondria, with the respiratory chain occurring there, are the power plants of cells and are increased in tissues with high energy requirements such as the heart. Complex I, the NADH dehydrogenase, is the first enzyme of the mitochondrial complex (MC) and therefore a potential target for MPI tracer. Insecticides such as rotenone or pyridaben are well known MC-I inhibitors and therefore interesting lead structures, to which a classical gallium chelator - like DOTA - could be coupled. Some 18F-labeled insecticides already showed good affinities for the enzyme and a high heart uptake.

Another approach uses hexadentate bis(salicylaldimine) chelators, which form positive lipophilic complexes by labeling with 68Ga and have the ability to penetrate the mitochondrial membrane, where they are enriched due to their cationic properties.

Figure 1: 68Ga-PET picture for visualization the myocard