Cardiovascular Molecular Imaging for Personalized Medicine

• Applicant: Professor Dr. Takahiro Higuchi
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Cardiology, Angiology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 262632242

The prevalence of heart failure caused by myocardial infarction has steadily increased while mortality decreased due to improved medical therapy with beta-blockers, and Renin-Angiotensin-Aldosteronesystem (RASS) blockers. In current clinical practice high-dose blockade is used for patients with acute myocardial infarction. It is initiated at incremental doses to avoid excessive hypotension. However, side effects are controversial with the incremental doses. Therefore, it would be ideal to have individual optimal-effective dose determination strategies.So far neurohumoral activation can be identified only systematically in the blood by circulating biomarkers. Our hypothesis is that in contrast the direct measurement of local cardiac neurohumoral activity will provide improved information for prognosis and therapy. The combination of noninvasive imaging with multiple radionuclides is an ideal approach for the analysis of neurohumoral activity, metabolism, and perfusion that may offer complementary information of the heart.Specifically, we will employ a rodent model of heart failure and radionuclide molecular imaging with dedicated high-resolution animal PET imaging system. Radionuclide tracers will include catecholamine analogues for sympathetic nervous system, AT-1 receptor antagonists for RAAS, and tracers for the analysis of perfusion and metabolism. The relationship between these biomarker alterations and subsequent left ventricular remodeling will be studied by serial scans. Finally, we will try to identify a minimal medication dose that blocks RAAS activation using titration via imaging. Thereby, the potential utilization of multimodality cardiovascular molecular imaging will be explored for personalizing medication dose of heart failure patients.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Stefan Frantz; Professor Dr. Ken Herrmann