Cardiovascular Molecular Imaging for Personalized Medicine
Cardiology, Angiology
Final Report Abstract
Generally intelligible overview of the obtained results and potential applications: Congestive Heart Failure (HF), mainly caused by coronary artery disease, is one of the most frequent causes of death among elder patients: more than 50,000 patients die annually from HF. A dramatic increase of this disease is envisaged in the near future and might affect almost every second patient in 2030. In the current project, we aimed to elucidate the underlying mechanisms of coronary artery disease and HF by using a dedicated assay of novel molecular, radiolabeled imaging agents. To assess the different underlying mechanism of HF, highly specific targeting radiotracers were investigated. In brief, a dedicated HF rat model in combination with small-animal imaging devices, namely micro-positron emission tomography (PET), was utilized. By using those highly targeting radionuclides, we obtained further insights into essential pathophysiological mechanisms of HF, such as a potential malfunction of the cardiac nervous system: an assay of different radiotracers in an HF rat model revealed novel aspects regarding the damage of innervation in the heart along with its recovery mechanism. Of note, the observed injury to cardiac sympathetic neurons after myocardial infarction was even larger than the perfusion defect (=area of less blood supply). The herein obtained data of our research might be helpful in detecting patient at risk at an earlier time point of disease onset or in identifying patients which are at high risk of HF-related sudden cardiac death. Moreover, by understanding the underlying concept of cardiac sympathetic nerve damage and restoration after myocardial infarction, a personalized treatment approach could be envisaged in the near future, as an appropriate time point of treatment could be determined. Additionally, this radionuclide-based assessment could potentially be applied in investigating the association between HF and other diseases, e.g. in patients suffering from depression. “Surprising results“: The concept of perfusion defect after myocardial infarction and HF is well-known. Moreover, several therapeutic approaches such as stenting the occlusion of a coronary artery (cardiac catheterization) in order to re-establish a constant blood supply to the heart muscle are routinely assessed in clinical practice. However, the high impact of damage to the cardiac sympathetic nerve system after myocardial infarction has not been expected and was quite surprising: it was even larger than the observed perfusion defect. Hence, injury to neurons in the heart seems to be even “more“ severe than a reduced blood flow to the heart muscle. This novel finding should be further confirmed in human hearts and might guide other treatments beyond re-establishing a constant blood supply of the coronary artery. Reports in the public media, such as in the Newsletter of the Comprehensive Heart Failure Center of the University Hospital Würzburg, highlighted the obtained results and the concept of cardiac molecular imaging.
Publications
- Retention Kinetics of the 18F-labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with 11C-HED and 123I-MIBG. J Nucl Med. 2015;Sep 56(9):1429-33
Werner RA, Rischpler C, Onthank D, Lapa C, Robinson S, Samnick S, Javadi M, Schwaiger M, Nekolla GS, Higuchi T
(See online at https://dx.doi.org/10.2967/jnumed.115.158493) - 11C-methionine PET of myocardial inflammation in a rat model of experimental autoimmune myocarditis. J Nucl Med. 2016 Dec;57(12):1985-1990
Maya Y, Werner RA, Schütz C, Wakabayashi H, Samnich S, Lapa C, Zechmeister C, Jahns R, Jahns V, Higuchi T
(See online at https://doi.org/10.2967/jnumed.116.174045) - Assessment of Coronary Flow Reserve using a Combination of Planar First-pass Angiography and Myocardial SPECT: Comparison with Myocardial 15O-Water PET. Int J Cardiol. 2016 Jul 29;222:209-212
Nose N, Fukushima K, Lapa C, Werner RA, Javadi MS, Taki J, Higuchi T
(See online at https://doi.org/10.1016/j.ijcard.2016.07.183) - Initial preclinical evaluation of 18F-fluorodesoxysorbitol as a Novel Functional Renal Imaging Agent. J Nucl Med. 2016 Oct;57(10):1625-1628
Wakabayashi H, Werner RA, Hayakawa N, Javadi MS, Xinyu C, Herrmann K, Rowe SP, Lapa C, Higuchi T
(See online at https://doi.org/10.2967/jnumed.116.172718) - Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by 11C-hydroxyephedrine. Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):312-8
Werner RA, Maya Y, Rischpler C, Javadi MS, Fukushima K, Lapa C, Herrmann K, Higuchi T
(See online at https://doi.org/10.1007/s00259-015-3171-x) - Impact of tissue photon attenuation in small animal cardiac PET imaging. Int J Cardiol. 2017 Jan 15;227:257-260
Hayakawa N, Yamane T, Arias-Loza PA, Shinaji T, Wakabayashi H, Lapa C, Werner RA, Mehrbod SJ, Pelzer T, Higuchi T
(See online at https://doi.org/10.1016/j.ijcard.2016.11.119) - Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model of Type 2 Diabetes Mellitus. Sci Rep. 2017 Dez 1
Lapa C, Arias-Loza P, Hayakawa N, Wakabayashi N, Werner RA, Chen X, Shinaji T, Herrmann K, Pelzer T, Higuchi T
(See online at https://doi.org/10.1038/s41598-017-17148-w)
