[¹⁸F]Fluoropyridine‐losartan: A new approach toward human Positron Emission Tomography imaging of Angiotensin II Type 1 receptors

Abstract

blocker losartan is used in patients with renal and cardiovascular diseases. [ 18 F]fluoropyridine-losartan has shown favorable binding profile for quantitative renal PET imaging of AT 1 R with selective binding in rats and pigs, low interference of radiometabolites and appropriate dosimetry for clinical translation. A new approach was developed to produce [ 18 F]fluoropyridine-losartan in very high molar activity. Automated radiosynthesis was performed in a three-step, two-pot, and two-HPLCpurification procedure within 2 h. Pure [ 18 F]FPyKYNE was obtained by radiofluorination of NO 2 PyKYNE and silica-gel-HPLC purification (40 ± 9%), preventing the formation of nitropyridine-losartan in the second step. Conjugation with trityl-losartan azide via click chemistry, followed by acid hydrolysis, C18-HPLC purification and reformulation provided [ 18 F]fluoropyridine-losartan in 11 ± 2% (decay-corrected from [ 18 F]fluoride, EOB). Using tris [(1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl)methyl]-amine (THPTA) as a Cu(I)stabilizing agent for coupling [ 18 F]FPyKYNE to the unprotected losartan azide afforded [ 18 F]fluoropyridine-losartan in similar yields (11 ± 3%, decaycorrected from [ 18 F]fluoride, EOB). Reverse-phase HPLC was optimized by reducing the pH of the mobile phase to achieve complete purification and high