Evaluation of [18F]FPyKYNE-losartan as a novel PET tracer for imaging kidney AT1 receptors in rats

330 Objectives The renin-angiotensin-system (RAS) is known to play an important role in the development and progression of cardiovascular disorders. In particular, angiotensin II type-1 receptor (AT1R) expression is altered in myocardial infarction, heart failure, chronic kidney disease and diabetes. The aim of this work was to evaluate the binding selectivity of [18F]FPyKYNE-losartan for quantifying renal AT1R in rats using micro-PET. Methods Male Sprague-Dawley rats (n=7) were administered i.v. [18F]FPyKYNE-losartan (0.4-1mCi) and imaged for 60 min with the Siemens Inveon PET scanner. Distribution volume (DV) was determined with Logan graphical analysis at 5-60 minutes, using the left atrial cavity for blood input function. Test-retest studies (n=4) were conducted within 7 days to assess process reproducibility. Subsets of rats (n=3-5) were co-injected with different doses of the AT1R antagonist, candesartan (2.5, 5 and 10 mg/kg). Another rat group (n=3) was injected with the AT2R antagonist, PD123,319 (5mg/kg) 5 min prior. Results PET images of normal rats displayed high renal uptake (SUV=1.52±0.58) and DV values from left kidney were 2.85±0.4 ml/g. The DVs test-retest variability was of (10.2±0.1%) exhibiting reproducibility. A significant (p Conclusions [18F]FPyKYNE-losartan displayed high kidney contrast PET images with reproducible DV values. A dose-response blockade with candesartan confirmed specific binding to renal AT1R. These findings support the use of this tracer for renal AT1R quantification with imaging. Research Support Ontario Preclinical Imaging Consortium, Ontario Research Foundation Canadian Institutes of Health Research