RT Journal Article
SR Electronic
T1 Myocardial infarction is associated with neuroinflammation - a systemic analysis using TSPO-targeted molecular imaging.
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 404
OP 404
VO 57
IS supplement 2
A1 Henri Christopher Hupe
A1 James Thackeray
A1 Johannes Postema
A1 Yong Wang
A1 Tobias Ludwig Ross
A1 Kai Wollert
A1 Jens Bankstahl
A1 Frank Bengel
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/404.abstract
AB 404Objectives Acute myocardial infarction (MI) evokes local and systemic inflammation, which may contribute to heart failure progression and cognitive decline. We aimed to assess heart-brain interaction after MI using the translocator protein (TSPO) ligand 18F-GE180 to serially image inflammation in both organs.Methods C57Bl/6 mice underwent coronary artery ligation (n=13) or sham procedure (n=6). Serial whole-body 18F-GE180 PET (11±2 MBq) was performed at 3d, 7d, 4 weeks and 8 weeks post-MI. Tracer binding was tested by coinjection of unlabeled compound. Infarct size and LV contractile function was evaluated by ECG-gated myocardial perfusion SPECT.Results MI mice exhibited a perfusion defect affecting 28±11% of the LV, and a progressive decline of LV ejection fraction (%, sham: 67±4; 1wk: 45±8; 4wk: 35±7; 8wk: 31±12, p<0.05). Uniform myocardial 18F-GE180 uptake was observed in sham operated mice and was stable over 8wks after surgery. At 3d post-MI, mice displayed elevated 18F-GE180 uptake in the infarct region in combination with elevated diffuse uptake by remote myocardium which was effectively blocked by coadministration of cold compound. Autoradiography confirmed the specific binding and regional pattern of 18F-GE180. Global myocardial uptake was elevated at 3d post-MI compared to matched sham mice (%ID/g, 7.7±1.1 vs 4.4±0.5, p<0.01). This was paralleled by an increase in whole brain TSPO binding (1.8±0.4 vs 1.3±0.5, p<0.01). The difference was mitigated at 4 wks post-surgery in myocardium (5.9±2.1, p=NS) and brain (1.3±0.4, p=NS). However, by 8wks, when EF was severely impaired (31±12%), enhanced TSPO signal recurred in global myocardium (7.0±2.0, p<0.01) and in whole brain (1.6±0.3, p=0.03). Heart and brain uptake of 18F-GE180 showed a significant correlation (r=0.78, p<0.01), reflecting the interaction of myocardial and neural inflammation. A mild correlation was identified between late 18F-GE180 myocardial uptake and EF (r=0.68, p=0.09).Conclusions TSPO is a useful target to study regional and systemic inflammation following MI. Myocardial inflammation is associated with neuroinflammation in a biphasic pattern, with increased TSPO binding in not only the acute phase after MI, but also in the chronic phase of heart failure, providing a potential rationale for the linkage between ischemic heart disease and cognitive decline.