Abstract:
: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 (AT1 R) antagonists, for in vivo positron emission tomography (PET). This allows the in vivo measurement of AT1 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 (IC50 =6.6 nm) and δ-position (IC50 =8.5 nm) of the aliphatic side chain) do not alter the binding properties of irbesartan (IC50 =1.6 nm). 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.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Hoffmann M,Chen X,Hirano M,Arimitsu K,Kimura H,Higuchi T,Decker Mdoi
10.1002/cmdc.201800638subject
Has Abstractpub_date
2018-12-06 00:00:00pages
2546-2557issue
23eissn
1860-7179issn
1860-7187journal_volume
13pub_type
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