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Abstract: Introduction: Two 7-fluoroimidazobenzodiazepines (AH114726 and GEH120348), analogs of flumazenil, were labeled with fluorine-18 and evaluated as alternative radioligands for in vivo imaging of the GABAA/benzodiazepine receptor by comparing them to [11C]flumazenil in rhesus monkey. Methods: Radiotracers were prepared from the corresponding nitro-precursors in an automated synthesis module, and primate imaging studies were conducted on a Concorde MicroPET P4 scanner. The brain was imaged for 60 (12×5min frames) or 90min (18×5min frames), and data was reconstructed using the 3D MAP algorithm. Specificity of [18F]AH114726 and [18F]GEH120348 was confirmed by displacement studies using unlabeled flumazenil. Results: [18F]GEH120348 and [18F]AH114726 were obtained in 13–24% yields (end of synthesis) with high chemical (>95%) and radiochemical (>99%) purities, and high specific activities (2061±985Ci/mmol). The in vivo pharmacokinetics of [18F]AH114726 and [18F]GEH120348 were determined in a non-human primate and directly compared with [11C]flumazenil. Both fluorine-18 radioligands showed time-dependent regional brain distributions that correlated with the distribution of [11C]flumazenil and the known concentrations of GABAA/benzodiazepine receptors in the monkey brain. [18F]AH114726 exhibited maximal brain uptake and tissue time-radioactivity curves that were most similar to [11C]flumazenil. In contrast, [18F]GEH120348 showed higher initial brain uptake but very different pharmacokinetics with continued accumulation of radioactivity into the cortical regions of high GABA/benzodiazepine receptor concentrations and very little clearance from the regions of low receptor densities. Rapid washout of both radiotracers occurred upon treatment with unlabeled flumazenil. Conclusion: The ease of the radiochemical synthesis, together with in vivo brain pharmacokinetics most similar to [11C]flumazenil, support that [18F]AH114726 is a suitable option for imaging the GABAA receptor. [Copyright &y& Elsevier]

Introduction: A novel one-pot method for preparing [18F]fluoromethylcholine ([18F]FCH) via in situ generation of [18F]fluoromethyl tosylate ([18F]FCH2OTs), and subsequent [18F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed. Methods: [18F]FCH was prepared using a GE TRACERlab FXFN, although the method should be readily adaptable to any other fluorine-18 synthesis module. Initially ditosylmethane was fluorinated to generate [18F]FCH2OTs. DMAE was then added and the reaction was heated at 120°C for 10min to generate [18F]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C18-Plus and CM-Light Sep-Pak cartridges to provide [18F]FCH formulated in USP saline. The formulated product was passed through a 0.22µm filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25h from end-of-bombardment. Results: Typical non-decay-corrected yields of [18F]FCH prepared using this method were 91mCi (7% non-decay corrected based upon ∼1.3Ci [18F]fluoride), and doses passed all other quality control (QC) tests. Conclusion: A one-pot liquid-phase synthesis of [18F]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6µg/10mL dose or ∼3ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies. [ABSTRACT FROM AUTHOR]

Purpose: To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods: Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2–0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use. Results: The decay corrected yield of 68Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined 66/67Ga) for a practical clinical product shelf-life. The activity yield of [68Ga]GaCl3 was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA). Conclusion: Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators. [ABSTRACT FROM AUTHOR]

Recent developments in 68 Ga-radiopharmaceuticals, including a number of regulatory approvals for clinical use, has created a hitherto unprecedented demand for 68 Ga. Reliable access to enough 68 Ga to meet growing clinical demand using only 68 Ge/ 68 Ga generators has been problematic in recent years. To address this challenge, we have optimized the direct production of 68 Ga on a cyclotron via the 68 Zn(p,n) 68 Ga reaction using a liquid target. This protocol describes the cyclotron-based production of [ 68 Ga]GaCl 3 implemented at the University of Michigan using a liquid target on GE PETtrace instrumentation. The protocol provides 56 ± 4 mCi (n = 3) of [ 68 Ga]GaCl 3 that meets the necessary quality control criteria to use for the preparation of 68 Ga-radiopharmaceuticals for human use., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Radiolabeled erythrocytes have multiple applications in nuclear medicine, including blood pool imaging. Historically they have been labeled with SPECT radionuclides. A PET blood pool imaging agent is highly desirable as it would improve clinical applications with better image quality and resolution, higher sensitivity, and dynamic scanning capabilities. With the coming of age of modern 68 Ge/ 68 Ga generator systems, gallium-68 is now widely accessible. In this paper we describe an updated method for the preparation of 68 Ga-labeled erythrocytes and their preliminary use in rodent blood pool imaging. A novel automated synthesis of [ 68 Ga]oxine using a 68 Ga/ 68 Ge generator and automated synthesis module is reported. [ 68 Ga]Oxine was synthesized in 50 ± 5% ( n = 3) non-decay corrected radiochemical yield and >99% radiochemical purity. Rat and human erythrocytes were successfully labeled with the complex in 42% RCY, and the 68 Ga-labeled erythrocytes have been shown to clearly image the blood pool in a healthy rat. Human erythrocytes labelled with [ 68 Ga]oxine were shown to be viable up to 2 hours post-labelling, and washout of the radiolabel was minimal up to 1 hour post-labelling. Further optimization of the labeling method to translate for use in human cardiac and oncologic blood pool PET imaging studies, is underway.