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[64Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent being investigated in clinical trials for malignant brain tumors. For the quality management of [64Cu]Cu-ATSM, understanding trace metal impurities' effects on the chelate formation of 64Cu and ATSM is important. In this study, we conducted coordination chemistry studies on metal–ATSM complexes. First, the effects of nonradioactive metal ions (Cu2+, Ni2+, Zn2+, and Fe2+) on the formation of [64Cu]Cu-ATSM were evaluated. When the amount of Cu2+ or Ni2+ added was 1.2 mol or 288 mol, equivalent to ATSM, the labeling yield of [64Cu]Cu-ATSM fell below 90%. Little effect was observed even when excess amounts of Zn2+ or Fe2+ were added to the ATSM. Second, these metals were reacted with ATSM, and chelate formation was measured using ultraviolet–visible (UV-Vis) absorption spectra. UV-Vis spectra showed a rapid formation of Cu2+ and the ATSM complex upon mixing. The rate of chelate formation by Ni2+ and ATSM was lower than that by Cu-ATSM. Zn2+ and Fe2+ showed much slower reactions with the ATSM than Ni2+. Trace amounts of Ni2+, Zn2+, and Fe2+ showed little effect on [64Cu]Cu-ATSM' quality, while the concentration of impurity Cu2+ must be controlled. These results can provide process management tools for radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Introduction Recently, 6-[(1-cyclobutylpiperidin-4-yl)oxy]-1-(6-[ 11 C]methoxypyridin-3-yl)-3,4-dihydroquinolin-2(1 H )-one ([ 11 C]TASP457, [ 11 C] 2 ) has been developed as a novel PET ligand for histamine H 3 receptors in brain. [ 11 C] 2 is potentially suitable for imaging H 3 receptors in rat and monkey brains, which has motivated us to perform first-in-human study of [ 11 C] 2 for qualifying H 3 receptors in human brain. In this paper, we report an efficient radiosynthesis of [ 11 C] 2 to obtain sufficient radioactivity and high quality for clinical application. Methods In manual synthesis, we optimized the reaction conditions of desmethyl precursor 1 , which contains a 2-hydroxypyridine moiety, with [ 11 C]MeI or [ 11 C]MeOTf. After optimization, we performed automated synthesis and quality control of [ 11 C] 2 . Results Bubbling [ 11 C]MeOTf into a heated mixture of precursor 1 and cesium carbonate in DMF at 100 °C for 90 s produced [ 11 C] 2 with decay-corrected radiochemical yields of (based on [ 11 C]CO 2 ) 7.9 ± 1.8% ( n = 78). The specific activity of [ 11 C] 2 was 156 ± 52 GBq/μmol ( n = 78) at the end of synthesis. The total synthesis time was approximately 35 min from the end of bombardment. All the quality control results of [ 11 C] 2 were in compliance with our in-house quality control/assurance specifications. Conclusion We radiosynthesized [ 11 C]TASP457 ([ 11 C] 2 ) with sufficient amounts of radioactivity and high quality for clinical usefulness. This radioligand is being used for PET assessment of H 3 receptors in human brain in our facility. [ABSTRACT FROM AUTHOR]

We report a novel labeling method for the rapid radiochlorination of aromatic compounds using no-carrier-added short-half-life radioactive chloride ions ([38,39Cl]Cl− and [34mCl]Cl−) and OXONE® (Sigma-Aldrich, Japan) as an oxidation reagent. The reaction of radioactive chloride ions with anisole in the presence of OXONE gave a mixture of p-[*Cl]chloroanisole and o-[*Cl]-chloroanisole, with a radiochemical conversion yield of more than 85% (not decay corrected) and selectivity of 7:3, within 10 min. Regioselective radioactive chlorination was achieved by chlorodestannylation of tributylstannyl compounds to afford the corresponding radiochlorinated compounds ( p-chloroanisole and m-chloroanisole) in satisfactory radiochemical yields (80-95% and 46-65%, respectively). Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Correction for ‘Developing native peptide-based radiotracers for PD-L1 PET imaging and improving imaging contrast by pegylation’ by Kuan Hu et al., Chem. Commun., 2019, DOI: URL10.1039/c9cc00445a/URL. [ABSTRACT FROM AUTHOR]

We have developed 8‐amino‐3‐(2S,5R‐dimethyl‐1‐piperidyl)‐[1,2,4]triazolo[4,3‐a]pyrazine‐5‐[11C]carbonitrile ([11C]MTP38) as a positron emission tomography (PET) tracer for the imaging of phosphodiesterase 7. For the fully automated production of [11C]MTP38 routinely and efficiently for clinical applications, we determined the radiosynthesis procedure of [11C]MTP38 using [11C]hydrogen cyanide ([11C]HCN) as a PET radiopharmaceutical. Radiosynthesis of [11C]MTP38 was performed using an automated 11C‐labeling synthesizer developed in‐house within 40 min after the end of irradiation. [11C]MTP38 was obtained with a relatively high radiochemical yield (33 ± 5.5% based on [11C]CO2 at the end of irradiation, decay‐corrected, n = 15), radiochemical purity (>97%, n = 15), and molar activity (47 ± 12 GBq/μmol at the end of synthesis, n = 15). All the results of the quality control (QC) testing for the [11C]MTP38 injection complied with our in‐house QC and quality assurance specifications. We successfully automated the radiosynthesis of [11C]MTP38 for clinical applications using an 11C‐labeling synthesizer and sterile isolator. Taken together, this protocol provides a new radiopharmaceutical [11C]MTP38 suitable for clinical applications. [ABSTRACT FROM AUTHOR]

Background: [18F]Fluoromisonidazole ([18F]FMISO) and 1-[18F]fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([18F]PM-PBB3 or [18F]APN-1607) are clinically used radiotracers for imaging hypoxia and tau pathology, respectively. Both radiotracers were produced by direct 18F-fluorination using the corresponding tosylate precursors 1 or 2 and [18F]F−, followed by the removal of protecting groups. In this study, we synthesized [18F]FMISO and [18F]PM-PBB3 by 18F-fluoroalkylation using [18F]epifluorohydrin ([18F]5) for clinical applications. Results: First, [18F]5 was synthesized by the reaction of 1,2-epoxypropyl tosylate (8) with [18F]F− and was purified by distillation. Subsequently, [18F]5 was reacted with 2-nitroimidazole (6) or PBB3 (7) as a precursor for 18F-labeling, and each reaction mixture was purified by preparative high-performance liquid chromatography and formulated to obtain the [18F]FMISO or [18F]PM-PBB3 injection. All synthetic sequences were performed using an automated 18F-labeling synthesizer. The obtained [18F]FMISO showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis (EOS); n = 8) with appropriate radiochemical yield based on [18F]F− (26 ± 7.5 % at EOS, decay-corrected; n = 8). The obtained [18F]PM-PBB3 also showed sufficient radioactivity (0.79 ± 0.10 GBq at EOS; n = 11) with appropriate radiochemical yield based on [18F]F− (16 ± 3.2 % at EOS, decay-corrected; n = 11). Conclusions: Both [18F]FMISO and [18F]PM-PBB3 injections were successfully synthesized with sufficient radioactivity by 18F-fluoroalkylation using [18F]5. [ABSTRACT FROM AUTHOR]

Abstract: In the present Letter, a fast and reproducible method for the synthesis of N-[13N]nitrosamines is reported. The labeling strategy is based on trapping [13N] in an anion exchange resin. The reaction with secondary amines in the presence of Ph3P and Br2 led to the formation of the desired nitrosamines in short reaction times (2min) with excellent radiochemical conversion (>45%). Final radiotracers were obtained after purification in good radiochemical yields (>30%, decay corrected). Radiochemical purity was above 99% in all cases. [Copyright &y& Elsevier]

Abstract We developed a new apparatus for the routine production of 64Cu in clinical use. The apparatus has many disposable parts that stabilize the product quality (such that there is a low deviation of the concentrations of impurity metals in the product) and reduce the work load of preparation for routine production. We also developed a new evaporator using near-infrared heaters for disposable use. We conducted a production test using the new apparatus and evaluated product quality. The product yield was 6.3 ± 0.32 GBq (end of bombardment) (N = 4), the product quality in terms of the concentrations of impurity metals (Cu2+, Ni2+, Fe3+, Zn2+, Mn2+) was as good as that usually achieved, likely on the order of parts per billion, and the preparation time was reduced from 2 days to 1 day. Highlights • An easy-handling separation system was developed using many disposable parts. • The concentration of impurity metals was likely on the order of parts per billion. • This quality was as good as that of our usually obtained product. • A new disposable evaporator was developed using a near-infrared heater. • The preparation time was reduced from 2 days to 1 day. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract DAA1106 (N -(2,5-dimethoxybenzyl)- N -(5-fluoro-2-phenoxyphenyl)acetamide), is a potent and selective ligand for the translocator protein (18 kDa, TSPO) in brain mitochondrial fractions of rats and monkey (K i = 0.043 and 0.188 nM, respectively). In this study, to translate [18F]DAA1106 for clinical studies, we performed automated syntheses of [18F]DAA1106 using the spirocyclic iodonium ylide (1) as a radiolabelling precursor and conducted preclinical studies including positron emission tomography (PET) imaging of TSPO in ischemic rat brains. Radiofluorination of the ylide precursor 1 with [18F]F−, followed by HPLC separation and formulation, produced the [18F]DAA1106 solution for injection in 6% average (n = 10) radiochemical yield (based on [18F]F−) with >98% radiochemical purity and molar activity of 60–100 GBq/μmol at the end of synthesis. The synthesis time was 87 min from the end of bombardment. The automated synthesis achieved [18F]DAA1106 with sufficient radioactivity available for preclinical and clinical use. Biodistribution study of [18F]DAA1106 showed a low uptake of radioactivity in the mouse bones. Metabolite analysis showed that >96% of total radioactivity in the mouse brain at 60 min after the radiotracer injection was unmetabolized [18F]DAA1106. PET study of ischemic rat brains visualized ischemic areas with a high uptake ratio (1.9 ± 0.3) compared with the contralateral side. We have provided evidence that [18F]DAA1106 could be routinely produced for clinical studies. [ABSTRACT FROM AUTHOR]

Introduction Copper-67 is an attractive beta emitter for targeted radionuclide therapy. However, the availability of 67 Cu limits its potential use in a wide range of applications. In this study, we propose an easy small-scale production of 67 Cu using 64 Ni target for a preclinical study. Methods 67 Cu was produced from an electrodeposited 64 Ni target via the 64 Ni(α, p) 67 Cu-reaction with a 36 MeV alpha beam at 15 eμA (electrical microampere) conducted for 7 h. The chemical separation process of 67 Cu from the 64 Ni target was performed following by our routine procedure of 64 Cu production using cation exchange resin, AG50W-X8, with minor modification. The target and its holder were redesigned in the preparation. Results The 67 Cu product was obtained with a yield of 55 ± 10 MBq at the end of bombardment (EOB), and the yield was 527 ± 96 kBq/μAh at the EOB. The copper impurity in the product was low (0.71 ± 0.21 μg) and the product was suitable for a preclinical study. Conclusions We produced 67 Cu with sufficient activity and quality for a preclinical study using a 64 Ni-target. This production method also showed advantages as a routine method, i.e., shorten the processing time, reducing the radiation exposure and ready target recycling, when compared with that of a conventional Zn-target used for 67 Cu production. [ABSTRACT FROM AUTHOR]

Introduction Copper-64 is an attractive radionuclide for positron emission tomography and is emerging as a radiotherapeutic agent. The demand of 64 Cu with low metallic impurities has increased because of its wide applications when incorporated with antibodies, peptides, and proteins. In this study, we propose a new separation method to produce high-quality 64 Cu using a cation exchange column, as well as an automated separation system suitable for large-scale production. Methods 64 Cu was produced from an electrodeposited 64 Ni target via the 64 Ni(p,n)-reaction with a 24 MeV HH+ beam at 10 eμA (electrical microampere) conducted for 1–3 h. The irradiated target was transported to a hot cell and disassembled remotely. 64 Cu was separated by a solvent mixture of HCl and acetone on a cation-exchange resin, AG50W-X8. The chemical purity of 64 Cu final product was evaluated using ion-chromatography coupled with a UV detector and inductively coupled plasma mass spectroscopy for quality as well as metallic impurities. Results We obtained 64 Cu in dried form at a yield of 5.2–13 GBq at the end of separation, or 521 ± 12 MBq/eμA h as the final product within 2.5 h of processing time. The metallic impurities were a satisfactory low level in the order of ppb. Major contaminants of Co and Ni were lower than those samples obtained by a widely accepted separation using an anion-exchange resin. Conclusion Using a cation-exchange resin and a systematic operation, we successfully reduced the contamination level of the 64 Cu product. As a straightforward separation method, which shortened the entire processing time, we obtained a satisfactory amount of high-quality 64 Cu available for routine use. [ABSTRACT FROM AUTHOR]

[ Thiocarbonyl -11C]disulfiram ([11C]DSF) was synthesized via iodine oxidation of [11C]diethylcarbamodithioic acid ([11C]DETC), which was prepared from [11C]carbon disulfide and diethylamine. The decay-corrected isolated radiochemical yield (RCY) of [11C]DSF was greatly affected by the addition of unlabeled carbon disulfide. In the presence of carbon disulfide, the RCY was increased up to 22% with low molar activity (A m , 0.27 GBq/μmol). On the other hand, [11C]DSF was obtained in 0.4% RCY with a high A m value (95 GBq/μmol) in the absence of carbon disulfide. The radiochemical purity of [11C]DSF was always >98%. The first PET study on [11C]DSF was performed in mice. A high uptake of radioactivity was observed in the liver, kidneys, and gallbladder. The uptake level and distribution pattern in mice were not significantly affected by the A m value of the [11C]DSF sample used. In vivo metabolite analysis showed the rapid decomposition of [11C]DSF in mouse plasma. [ABSTRACT FROM AUTHOR]