Why the study?
The RAAS regulates blood pressure and electrolyte balance, and novel 18F-labeled irbesartan derivatives were sought for in vivo PET imaging of AT1R expression.
Does an 18F-labeled derivative of irbesartan allow for specific in vivo PET imaging of AT1R expression in healthy rats and pigs?
Does an 18F-labeled derivative of irbesartan allow for specific in vivo PET imaging of AT1R expression in healthy rats and pigs?
A novel 18F-labeled irbesartan derivative demonstrates preserved AT1R binding affinity and specific in vivo renal uptake, suggesting potential for PET imaging of AT1R expression.
Facilitates preclinical AT1R PET imaging; leaves open clinical translation in hypertension and HF.
The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18 F‐labeled derivative of the drug irbesartan, one of the most prescribed angiotensin II type 1 receptor (AT 1 R) antagonists, for in vivo positron emission tomography (PET). This allows the in vivo measurement of AT 1 R expression, and thus the evaluation of functional changes in its expression under pathophysiological conditions. We followed various synthetic approaches optimized for the introduction of fluorine into different positions of the aliphatic side chain of irbesartan. Radioligand binding studies revealed that fluorine atoms at specified positions (α‐position (IC 50 =6.6 n m ) and δ‐position (IC 50 =8.5 n m ) of the aliphatic side chain) do not alter the binding properties of irbesartan (IC 50 =1.6 n m ). After successful radiolabeling with fluorine‐18 in a radiochemical yield of 11 %, we observed high renal uptake in healthy rats and pigs, which could be decreased by pretreatment with the parent compound irbesartan.
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Hoffmann et al. (2018) studied this question.
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