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A new method for the synthesis of the highly selective delta opioid receptor (DOR) antagonist radiotracer N1 '-([11 C]methyl)naltrindole ([11 C]MeNTI) is described. The original synthesis required hydrogenation of a benzyl protecting group after 11 C-labeling, which is challenging in modern radiochemistry laboratories that tend to be heavily automated and operate according to current good manufacturing practice. To address this challenge, we describe development of a novel MeNTI precursor bearing a methoxymethyl acetal (MOM) protecting group, which is easily removed with HCl, and employ it in an updated synthesis of [11 C]MeNTI. The new synthesis is fully automated and validated for clinical use. The total synthesis time is 45 min and provides [11 C]MeNTI in good activity yield (49 ± 8 mCi), molar activity (3,926 ± 326 Ci/mmol) and radiochemical purity (97% ± 2%).

When utilizing [18F]tetrabutylammonium fluoride ([18F]TBAF) in the synthesis of 18F-labeled radiotracers for clinical positron emission tomography (PET) imaging, it is necessary to confirm that residual TBA levels in formulated doses do not exceed established specifications (≤2.6 mg per patient dose). Historically this has been accomplished using HPLC, but this is time consuming for short-lived PET radiotracers and limited by the need for expensive equipment. This motivated us to introduce a TLC spot test for determining residual TBA, and we have developed a new method which employs the Dragendorff reagent. Herein we report details of the TLC method and use it to quantify residual TBA in different formulations of 6-[18F]fluoro-DOPA.

A new method for the synthesis of the highly selective delta opioid receptor (DOR) antagonist radiotracer N

Background In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research Committee (RDRC) as long as certain requirements are met. Firstly, the research must be for basic science and cannot be intended for immediate therapeutic or diagnostic purposes, or to determine the safety and effectiveness of the PET radiotracer. Secondly, the PET radiotracer must be generally recognized as safe and effective. Specifically, the mass dose to be administered must not cause any clinically detectable pharmacological effect in humans, and the radiation dose to be administered must be the smallest dose practical to perform the study and not exceed regulatory dose limits within a 1-year period. In our experience, the main barrier to using a PET radiotracer under RDRC approval is accessing the required information about mass and radioactive dosing. Results The University of Michigan (UM) has a long history of using PET radiotracers in clinical research studies. Herein we provide dosing information for 55 radiotracers that will enable other PET Centers to use them under the approval of their own RDRC committees. Conclusions The data provided herein will streamline future RDRC approval, and facilitate further basic science investigation of 55 PET radiotracers that target functionally relevant biomarkers in high impact disease states.

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