Abstract
5 Objectives The novel PET tracer C-11 KR31173 (KR) binds specifically to the Angiotensin II type I receptor (AT1R), and has been successfully used in animals for imaging of healthy and post-infarction hearts. We aimed to study the global and regional myocardial retention, binding specificity and imaging feasibility of KR in the human heart, and to compare these characteristics with prior results from pig studies. Methods Four healthy volunteers (HV) were imaged at baseline using a 40-min dynamic PET acquisition after KR injection(740 MBq). To determine the specificity of myocardial uptake, 2 HV returned 24 hrs later and received a single 40mg dose of Olmesartan, 3 hrs prior to KR. Three healthy pigs from a previous protocol were used for comparison. Results Myocardial uptake of KR was stable over time both in the human and porcine heart. A global myocardial KR retention(KR-ret) index was obtained, which was 1.27±0.09 in HV, and decreased to 0.63±0.17%/min (51% blockage) after Olmesartan. In pigs, global KR-ret was significantly higher (2.64±0.81%/min,P=0.018) compared to HV. While regional retention was homogeneous in the porcine heart, KR-ret was significantly higher in the inferior wall than in the anterior wall in HV (1.54±0.25 vs. 1.04±0.07%/min). This difference was associated with intense liver activity in close proximity to the heart, resulting in scatter and spillover problems. Conclusions In this translational study, noninvasive imaging suggests higher global myocardial AT1R expression in pigs when compared to humans. There is regional heterogeneity in the human heart, associated with intense KR liver activity, which may impose a major limitation in humans. However, KR may still be feasible for evaluation of conditions where AT1R expression is expected to be globally abnormal. Functional and/or anatomical species differences are often overlooked in translational research, the presented data underscore the importance of such studies
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