Problem being addressed. Causing 4 million deaths in Europe annually, the Heart Failure (HF) epidemic caused by inflammation of the heart continues to rise, while long-term prognosis of this devastating disease remains poor. Alterations of hormonal cardiac conditions play a crucial role in HF development. Drugs targeting those underlying mechanism have opened the door for promising therapeutic approaches in HF treatment, but it remains unclear which patient may benefit the most. Why is it important for society? Costs attributable to HF are expected to triple within the next decade. Despite promising efforts in recent years, mortality and morbidity remain high. Thus, novel non-invasive strategies for the reliable assessment of altered hormonal conditions in HF have intensively been sought for and ideally, such novel biomarkers may pave the way for personalized treatment. As a novel imaging modality, molecular imaging allows for precise assessment of the current hormonal status of the heart. During this research project, we aimed to elucidate if such molecular imaging techniques can differentiate between different inflammation states of the heart and thereby allow for imaging-guided treatment optimization in HF patients. For this purpose a set of different molecular imaging probes (radiotracers) were studied in a small animal model of cardiac inflammation. Overall objectives. For a molecular imaging PET scan, a radioactive substance is injected and the patient is passed through the imaging device to detect energy emission of the radioactive substance within the body (e.g. to assess treatment response for an anti-cancer drug). Notably, as a counterpart to human PET scanners, small-animal molecular imaging PET systems have recently been introduced. Such systems allow for serial in-vivo imaging in rodents and facilitate translation of new imaging strategies from bench to bedside. In the present project, we established a rodent model of cardiac inflammation, which led to a broad range of immune cell activation. Thereafter, a set of radiotracers, which target alterations of hormonal cardiac conditions and activated macrophages, were investigated. First, we could prove that these radiotracers for imaging the cardiac hormonal status indeed mimic the physiological neuronal cell-cell interaction. Second, we were able to show that using these tracers, molecular imaging can differentiate between active and chronic inflammation in the heart. Notably, these PET-based imaging results were also further corroborated by histological analyses at each disease stage serving as reference standard. After completing these experiments at the American host institution, an extensive knowledge exchange to the German home institution has been conducted and thus, the European Research Area has been strengthened. Conclusions and Outlook. The obtained results of the current preclinical project are encouraging and demonstrate that molecular imaging could potentially be applied for risk stratification, e.g. by monitoring treatment response using anti-inflammatory medications. Nonetheless, further research is warranted to investigate the benefit of such a molecular cardiac imaging approach and to finally transfer it into a human setting.
