Key result
The novel PET tracer [18F]FV45 demonstrated an AT1 receptor binding affinity of 14.6 nM, comparable to valsartan, and showed specific, blockable kidney uptake in rats.
[18F]FV45 is a novel PET tracer derived from valsartan that successfully visualizes AT1 receptor distribution in vivo, offering a potential new tool for assessing renin-angiotensin system function.
May advance preclinical RAS imaging research; leaves open human validation for cardiovascular use.
High Resolution Image Download MS PowerPoint Slide Renin–angiotensin system (RAS) plays an important role in the regulation of blood pressure and hormonal balance. Using positron emission tomography (PET) technology, it is possible to monitor the physiological and pathological distribution of angiotensin II type 1 receptors (AT 1 ), which reflects the functionality of RAS. A new 18 F-labeled PET tracer derived from the clinically used AT 1 antagonist valsartan showing the least possible chemical alteration from the valsartan structure has been designed and synthesized with several strategies, which can be applied for the syntheses of further derivatives. Radioligand binding study showed that the cold reference FV45 ( K i 14.6 nM) has almost equivalent binding affinity as its lead valsartan ( K i 11.8 nM) and angiotensin II ( K i 1.7 nM). Successful radiolabeling of FV45 in a one-pot radiofluorination followed by the deprotection procedure with 21.8 ± 8.5% radiochemical yield and >99% radiochemical purity ( n = 5) enabled a distribution study in rats and opened a path to straightforward large-scale production. A fast and clear kidney uptake could be observed, and this renal uptake could be selectively blocked by pretreatment with AT 1 -selective antagonist valsartan. Overall, as the first 18 F-labeled PET tracer based on a derivation from clinically used drug valsartan with almost identical chemical structure, [ 18 F]FV45 will be a new tool for assessing the RAS function by visualizing AT 1 receptor distributions and providing further information regarding cardiovascular system malfunction as well as possible applications in inflammation research and cancer diagnosis.
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Chen et al. (2018) studied Healthy. [18F]FV45 vs. Valsartan pretreatment was evaluated on Binding affinity (Ki) to human AT1 receptors. The novel PET tracer [18F]FV45 demonstrated an AT1 receptor binding affinity of 14.6 nM, comparable to valsartan, and showed specific, blockable kidney uptake in rats.
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