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Histone deacetylases (HDACs) mediate epigenetic mechanisms implicated in a broad range of central nervous system dysfunction, including neurodegenerative diseases and neuropsychiatric disorders. [11C]Martinostat allows in vivo quantification of class I/IIb HDACs and may be useful for the quantification of drug–occupancy relationship, facilitating drug development for disease modifying therapies. The present study reports a radiosynthesis of [11C]martinostat using [11C]methyl triflate in ethanol, as opposed to the originally described synthesis using [11C]methyl iodide and DMSO. [11C]Methyl triflate is trapped in a solution of 2 mg of precursor 1 dissolved in anhydrous ethanol (400 μl), reacted at ambient temperature for 5 min and purified by high‐performance liquid chromatography; 1.5–1.8 GBq (41–48 mCi; n = 3) of formulated [11C]martinostat was obtained from solid‐phase extraction using a hydrophilic–lipophilic cartridge in a radiochemical yield of 11.4% ± 1.1% (nondecay corrected to trapped [11C]MeI), with a molar activity of 369 ± 53 GBq/μmol (9.97 ± 1.3 Ci/μmol) at the end of synthesis (40 min) and validated for human use. This methodology was used at our production site to produce [11C]martinostat in sufficient quantities of activity to scan humans, including losses incurred from decay during pre‐release quality control testing. [ABSTRACT FROM AUTHOR]

Current challenges facing us in developing dedicated position emission tomography (PET) system for metabolic breast mammography (PEM) and small animal (ANIPET) are to achieve high spatial resolution (less than 2 mm) and high efficiency. It is also crucial to extend the sensitive areas of PEM detectors to their periphery in order to overcome the difficulty in imaging near a patient's chest wall. This limitation of the periphery dead region was revealed in the clinical trials of our previously developed PEM-I system. In the new study, we developed prototype detectors by using position-sensitive photomultiplier tubes (PS-PMTs) and pixelated bismuth germanate (BGO) crystals with depth encoding scheme to detect and localize gamma rays. The procedures in crystal processing include cutting, polishing, encapsulating, separating, and re-gluing. We also developed front-end electronic circuits including high-voltage dividers, anode resistor chains, position readout circuits, and last dynode timing circuits. Methods for combining four PS-PMTs with simple X+, X-, Y+, Y- outputs have been developed to further simplify the position recording. The detectors were constructed in the structure of array (two in the system)--module (four in each array)--unit (four in each module). The basic unit of one crystal and one PS-PMT can be field replaceable. Our new prototype detectors show that the proposed PEM-II system has a spatial resolution of 1.8 mm (versus 2.8 mm in PEM-I), a timing resolution of 10.3 ns (versus 12 ns in PEM-I), and a field-of-view of 88 mm x 88 mm (versus 64 mm x 56 mm in PEM-I). Compared with our previous PEM-I system, it demonstrates that the design improves the spatial resolution, enhances the detector field-of-view, and significantly reduces the peripheral dead regions. Index Terms--Bismuth germanate (BGO) crystal, position-sensitive photomultiplier tube (PS-PMT), positron emission mammography (PEM), positron emission tomography (PET).

Pittsburgh compound B ([11C]PiB) is the gold standard positron emission tomography (PET) tracer for the in vivo imaging of amyloid plaques. Currently, it is synthesized by either solution chemistry or using a 'dry loop' approach followed by HPLC purification within 30 minutes starting from [11C]CO2. Here, we report a novel, highly efficient solid phase supported carbon-11 radiolabeling procedure using commercially available disposable tC18 cartridge as a '3-in-1' entity: reactor, purifier, and solvent replacement system. [11C]PiB is synthesized by passing gaseous [11C]CH3OTf through a tC18 cartridge preloaded with a solution of precursor. Successive elution with aqueous ethanol solutions allows for nearly quantitative separation of the reaction mixture to provide chemically and radiochemically pure PET tracer. [11C]PiB suitable for human injection is produced within 10 minutes starting from [11C]CH3OTf (20 min from [11C]CO2) in 22% isolated yield not corrected for decay and molar activity of 190 GBq/μmol using 0.2 mg of precursor. This technique reduces the amount of precursor and other supplies, avoids use of preparative HPLC and toxic solvents, and decreases the time between consecutive production batches. Solid phase supported technique can facilitate [11C]PiB production compliant with Good Manufacturing Practice (GMP) and improve synthesis reliability. [ABSTRACT FROM AUTHOR]

Current challenges facing us in developing dedicated position emission tomography (PET) system for metabolic breast mammography (PEM) and small animal (ANIPET) are to achieve high spatial resolution (less than 2 mm) and high efficiency. It is also crucial to extend the sensitive areas of PEM detectors to their periphery in order to overcome the difficulty in imaging near a patient's chest wall. This limitation of the periphery dead region was revealed in the clinical trials of our previously developed PEM-I system. In the new study, we developed prototype detectors by using position-sensitive photomultiplier tubes (PS-PMTs) and pixelated bismuth germanate (BGO) crystals with depth encoding scheme to detect and localize gamma rays. The procedures in crystal processing include cutting, polishing, encapsulating, separating, and re-gluing. We also developed front-end electronic circuits including high-voltage dividers, anode resistor chains, position readout circuits, and last dynode timing circuits. Methods for combining four PS-PMTs with simple X+, X-, Y+, Y- outputs have been developed to further simplify the position recording. The detectors were constructed in the structure of array (two in the system)--module (four in each array)--unit (four in each module). The basic unit of one crystal and one PS-PMT can be field replaceable. Our new prototype detectors show that the proposed PEM-II system has a spatial resolution of 1.8 mm (versus 2.8 mm in PEM-I), a timing resolution of 10.3 ns (versus 12 ns in PEM-I), and a field-of-view of 88 mm x 88 mm (versus 64 mm x 56 mm in PEM-I). Compared with our previous PEM-I system, it demonstrates that the design improves the spatial... [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Radiolabeling is critical in complex chemical reactions involving positron emission tomography (PET) radiotracer production. The process is now automated within a synthesis module to enhance efficiency and reduce radiation exposure. The key to this automation is the use of radiation detectors to monitor radioactivity transfer and ensure the progression of reactions. However, the high cost of these detectors has motivated the need for a more affordable alternative.This study aimed to develop a compact and cost‐efficient detector using scintillating fibers and silicon photomultipliers (SiPMs) to track radioactivity throughout PET radiotracer production.Monte Carlo simulations were performed with the Geant4‐based M‐TAG software for four detector geometries (single fiber, single fiber with bolus, 16‐fiber bundle, and spiral) to optimize the detector construction for better detection efficiency. The simulations scored the energy deposited into the scintillating fibers per simulated particle, which was used to estimate the expected voltage pulse height from the SiPM considering the total light collection efficiency. Based on the simulation results, two detector configurations (16‐fiber bundle and spiral fiber) were constructed using plastic scintillating fibers, optical fibers, a 6 mm ×$\times$ 6 mm SiPM, and commonly available electronic components. The detectors were calibrated using a Fluorine‐18 (18F$^{18}{\rm F}$) source with typical activity levels used in radiotracer production. Detector performances were subsequently evaluated through linearity tests and measurement uncertainty assessments. Errors up to ±5%$\pm 5\%$ were considered acceptable for troubleshooting purposes.The calibration curves showed a linear response with changing activity for both detectors. The calibrated detectors offered real‐time activity measurements ranging from 0.10 to 49.41 GBq, with a 3‐s refresh rate. In the activity range above 0.145 GBq, the uncertainties were less than 5%$5\%$ for both the 16‐fiber and spiral configurations. The spiral detector recorded a signal with a half‐life of 105.88±0.40$105.88 \pm 0.40$ min, closely aligning with the reference half‐life of 18F$^{18}{\rm F}$.Cost‐efficient plastic scintillation fiber detectors were developed to facilitate the troubleshooting of automated synthesis of PET radiotracers. [ABSTRACT FROM AUTHOR]

Abstract: We synthesized [11C]methyl azide ([11C]MeA) by reacting [11C]methyl iodide ([11C]MeI) in situ with an azide-donor and used it in the synthesis of 11C-labeled 1,2,3-triazoles. A one-pot click approach comprised the infusion of gaseous [11C]MeI into a mixture of NaN3, ethynylbenzene, and CuI in water at a temperature of 100°C yielding the 11C-triazole in radiochemical yields (RCY) of 25%. In a two-step labeling protocol, we synthesized the [11C]MeA in acetonitrile in advance to the click step. Using the more soluble complex as source of , a much higher trapping efficiency of [11C]MeI in this solvent ensured an almost quantitative conversion of [11C]MeI to [11C]MeA within 5–10min at room temperature. The [11C]MeA was thereafter reacted with ethynylbenzene at 100°C yielding 1-[11C]methyl-4-phenyl-1H-1,2,3-triazole in preparative RCY of 60%. As a final proof of applicability, we used 11C-click-chemistry for the labeling of N-terminal 4-ethynylbenzene derivatized d-Glu–d-Tyr–[Cys–Tyr–Trp–Lys–Thr–Cys]–Thr, a cyclic water-soluble Tyr3-octreotate derivative. [Copyright &y& Elsevier]

Abstract: Introduction: The central benzodiazepine receptor (cBZR)–gamma-aminobutyric acid (GABAA) receptor complex in the human brain plays an important role in many neurological and psychiatric disorders. 18F-Labeled flumazenil ([18F]FZ) provides a potentially useful tracer to investigate those disorders by means of positron emission tomography (PET). Methods: [18F]Flumazenil was synthesized from its nitro-precursor Ro 15-2344 in DMF at high temperatures between 150°C and 160°C. Other solvents like acetonitrile and dimethylsulfoxide were also investigated as reaction media. A new HPLC method for the final purification of [18F]FZ was developed to circumvent some difficulties associated with a previously published procedure sometimes led to a contamination of [18F]FZ with Ro 15-2344. The final purification of the radiotracer was achieved using a Waters Symmetry Prep C18 HPLC column with elution with 0.05 M sodium acetate (NaOAc) buffer (pH 5)/THF/MeOH (80:10:10). Results: [18F]FZ could be synthesized in reproducible radiochemical yields (RCYs) of 15–20% (decay corrected to EOB) after 80 min overall synthesis time. The synthesized [18F]FZ was applied for the first time in a human PET study in a patient with ischemic right middle cerebral artery stroke using the HRRT high-resolution research scanner (Siemens Medical Solution, Knoxville, TN, USA). Conclusions: [18F]FZ is a potentially useful GABA receptor-binding PET ligand. A modified procedure for its preparation in reproducibly high radiochemical yields has been described and the [18F]FZ thus produced has been used successfully in a pilot clinical study. [Copyright &y& Elsevier]