Synthesis and evaluation of [18F]FEtLos and [18F]AMBF3Los as novel 18F-labelled losartan derivatives for molecular imaging of angiotensin II type 1 receptors
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Losartan is widely used in clinics to treat cardiovascular related diseases by selectively
blocking the angiotensin II type 1 receptors (AT1Rs), which regulate the renin-angiotensin system
(RAS). Therefore, monitoring the physiological and pathological biodistribution of AT1R using
positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS.
Herein, we describe the synthesis and characterization of two novel losartan derivatives PET
tracers, [18F]fluoroethyl-losartan ([18F]FEtLos) and [18F]ammoniomethyltrifluoroborate-losartan
([18F]AMBF3Los). [18F]FEtLos was radiolabeled by 18F-fluoroalkylation of losartan potassium using
the prosthetic group 2-[18F]fluoroethyl tosylate; whereas [18F]AMBF3Los was prepared following an
one-step 18F-19F isotopic exchange reaction, in an overall yield of 2.7 ± 0.9% and 11 ± 4%, respectively,
with high radiochemical purity (>95%). Binding competition assays in AT1R-expressing membranes
showed that AMBF3Los presented an almost equivalent binding affinity (Ki 7.9 nM) as the cold
reference Losartan (Ki 1.5 nM), unlike FEtLos (Ki 2000 nM). In vitro and in vivo assays showed that
[18F]AMBF3Los displayed a good binding affinity for AT1R-overexpressing CHO cells and was able
to specifically bind to renal AT1R. Hence, our data demonstrate [18F]AMBF3Los as a new tool for PET
imaging of AT1R with possible applications for the diagnosis of cardiovascular, inflammatory and
cancer diseases.
Como referenciar
PIJEIRA, MARTHA S.O.; NUNES, PAULO S.G.; SANTOS, SOFIA N. dos; ZHANG, ZHENGXING; NARIO, ARIAN P.; PERINI, EFRAIN A.; TURATO, WALTER M.; RIERA, ZALUA R.; CHAMMAS, ROGER; ELSINGA, PHILIP H.; LIN, KUO-SHYAN; CARVALHO, IVONE; BERNARDES, EMERSON S. Synthesis and evaluation of [18F]FEtLos and [18F]AMBF3Los as novel 18F-labelled losartan derivatives for molecular imaging of angiotensin II type 1 receptors. Molecules, v. 25, n. 8, p. 1-21, 2020. DOI: 10.3390/molecules25081872. Disponível em: http://repositorio.ipen.br/handle/123456789/31407. Acesso em: 31 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.