Analysis of [11C]methyl-candesartan kinetics in the rat kidney for the assessment of angiotensin II type 1 receptor density in vivo with PET

Introduction: Angiotensin II type 1 (AT1) receptors play a key role in the regulation of renal and cardiovascular functions and have been implicated in the pathogenesis of many diseases. The aim of this study was to assess binding of the novel radioligand [11C]methyl-candesartan to AT1 receptors in the rat kidney in vivo with PET. Methods: Dynamic PET images were acquired for 60 min at baseline, with coinjection of candesartan (5 mg/kg), and after injection of PD123,319 (5 mg/kg). Volumes of distribution (RC∙ VT) were estimated with a two-compartment model, by Logan analysis, and by taking the tissue-to-plasma activity ratio at 50–60 min post-injection. Results: The two-compartment model did not describe the kinetics at baseline adequately and the baseline scans were too short to obtain accurate estimates of RC∙ VT with the Logan approach. Based on the tissue-to-plasma ratios, roughly one-third of VT at baseline could be attributed to AT1 receptor binding. There were no indications of AT2 receptor binding in the rat kidney. Conclusion: It may be possible to detect changes in AT1 receptor density in the rat kidney in vivo with [11C]methyl-candesartan and PET. Imaging AT1 receptors with PET may provide valuable information on the role of these receptors in the pathogenesis of diseases such as hypertension, diabetic nephropathy, ventricular remodeling, and heart failure