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Angiotensin II type 1 receptors (AT1R) blocker losartan is used in patients with renal and cardiovascular diseases. [18F]fluoropyridine‐losartan has shown favorable binding profile for quantitative renal PET imaging of AT1R with selective binding in rats and pigs, low interference of radiometabolites and appropriate dosimetry for clinical translation. A new approach was developed to produce [18F]fluoropyridine‐losartan in very high molar activity. Automated radiosynthesis was performed in a three‐step, two‐pot, and two‐HPLC‐purification procedure within 2 h. Pure [18F]FPyKYNE was obtained by radiofluorination of NO2PyKYNE 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 [18F]fluoropyridine‐losartan in 11 ± 2% (decay‐corrected from [18F]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 [18F]FPyKYNE to the unprotected losartan azide afforded [18F]fluoropyridine‐losartan in similar yields (11 ± 3%, decay‐corrected from [18F]fluoride, EOB). Reverse‐phase HPLC was optimized by reducing the pH of the mobile phase to achieve complete purification and high molar activities (467 ± 60 GBq/μmol). The use of radioprotectants prevented tracer radiolysis for 10 h (RCP > 99%). The product passed the quality control testing. This reproducible automated radiosynthesis process will allow in vivo PET imaging of AT1R expression in several diseases. [ABSTRACT FROM AUTHOR]

Candesartan is a clinically approved angiotensin II type 1 receptor (AT1R)‐blocker that selectively binds AT1Rs in high affinity. We report here the radiosynthesis and automation of the novel [18F]fluorobenzyl derivative of Candesartan using the Sonogashira cross‐coupling reaction. [18F]Fluorobenzyl‐Candesartan ([18F]7) was developed from 4‐[18F]fluoroiodobenzene ([18F]FIB) that was conjugated with alkyne‐trityl‐candesartan with the assistance of a Pd (PPh3)4/CuI catalyst followed by acid deprotection. The three‐step two‐reactor 2‐HPLC purification process was automated resulting in >90% pure [18F]7 in a RCY of 4.6 ± 1.1% (decay corrected from EOB) and molar activities of 1,406‐5,513 GBq/mmol. [18F]FIB was reproducibly obtained by direct radiofluorination of the mono‐iodinated triphenylsulfonium salt in the presence of K222/K2CO3 in an ~30% yield (decay‐corrected). [18F]7 was stable (>97%) up to 4 h in solution and up to 1 h in rat plasma at 37°C. However, the use of Sonogashira cross‐coupling reaction to produce [18F]7 in high yields and molar activities was found to be challenging for routine use in radiochemistry labs. [ABSTRACT FROM AUTHOR]

Neprilysin, also known as neutral endopeptidase, is a cell surface membrane metalo‐endopeptidase that cleaves various peptides. Altered neprilysin expression has been correlated with various cancers and cardiovascular diseases. In this work, we present the radiosynthesis of the novel O‐11C‐methylated derivative of LBQ657 (a potent neprilysin inhibitor). (2R,4S)‐5‐(Biphenyl‐4‐yl)‐4‐[(3‐carboxypropionyl)amino]‐2‐methylpentanoic acid [11C]methyl ester ([11C]MeOLBQ) is an analog of sacubitril where the alkyl ester is a 11C‐methyl instead of an ethyl. [11C]MeOLBQ was produced in a one‐pot two‐step synthesis. The O‐11C‐methylation of the pentanoic acid part was done with [11C]methyl triflate followed by the deprotection of the tert‐butyl ester precursor in acidic conditions. [11C]MeOLBQ ([11C]7) was produced in 9.5 ± 2.5% RCY (25 ± 6% decay‐corrected from [11C]CO2, n = 3) high molar activity 348 ± 100 GBq/μmol (9425 ± 2720 mCi/μmol) at EOS, in high chemical (>95%) and radiochemical (>99%) purities. The total synthesis time including HPLC purification and reformulation was 29 minutes. To our knowledge, this is the first PET‐labeled analog of the clinically used NEP inhibitor sacubitril. [ABSTRACT FROM AUTHOR]

[18F]DCFPyL is a clinical‐stage PET radiotracer used to image prostate cancer. This report details the efficient production of [18F]DCFPyL using single‐step direct radiofluorination, without the use of carboxylic acid‐protecting groups. Radiolabeling reaction optimization studies revealed an inverse correlation between the amount of precursor used and the radiochemical yield. This simplified approach enabled automated preparation of [18F]DCFPyL within 28 minutes using HPLC purification (26% ± 6%, at EOS, n = 4), which was then scaled up for large‐batch production to generate 1.46 ± 0.23 Ci of [18F]DCFPyL at EOS (n = 7) in high molar activity (37 933 ± 4158 mCi/μmol, 1403 ± 153 GBq/μmol, at EOS, n = 7). Further, this work enabled the development of [18F]DCFPyL production in 21 minutes using an easy cartridge‐based purification (25% ± 9% radiochemical yield, at EOS, n = 3). [ABSTRACT FROM AUTHOR]