Redefining AT1 Receptor PET Imaging: Introducing the Radiotracer [¹⁸F]DR29

AT1R (angiotensin II type 1 receptors) are central to the renin-angiotensin system and are involved in regulating blood pressure and renal physiology. This study introduces [¹⁸F]DR29, a fluorine-18-labeled radiotracer for positron emission tomography imaging, to enable noninvasive visualization of AT1R expression. Its potential applications in understanding AT1R-associated renal processes are explored in healthy and hypertensive rat models.

Radiolabeling was established, and biodistribution studies were conducted on healthy Wistar rats with and without the AT1R antagonist candesartan and transporter inhibitors. Dynamic positron emission tomography imaging assessed tracer specificity, and feasibility for renal AT1R quantification was explored using a hypertensive rat model.

[¹⁸F]DR29 was radiolabeled with a yield of 36±6%. High kidney uptake was observed, significantly reduced by candesartan (kidney-to-blood ratio, 0.43±0.01 versus 4.54±1.59 in vehicle, where vehicle refers to saline without any treatment). Transporter inhibition protocols targeting organic anion transporting polypeptides (liver) and organic anion transporters (kidneys) successfully reduced radiotracer clearance, increasing the specific accumulation of [¹⁸F]DR29 in the kidneys and improving renal imaging contrast. Positron emission tomography imaging revealed rapid kidney uptake and stable retention over 2 hours. In hypertensive rats, kidney uptake was higher, aligning with AT1R expression levels.

These results support [¹⁸F]DR29 as a promising tool for the noninvasive evaluation of renal AT1R expression in healthy and diseased states. The findings lay the groundwork for clinical translation, offering potential applications in diagnosing and managing kidney-related diseases, including hypertension and other conditions involving AT1R dysregulation.