Background and Purpose: The cannabinoid type 2 receptors (CB2R) represent a target of increasing importance in neuroimaging due to its upregulation under various neuropathological conditions. Previous evaluation of [18F]JHU94620 for the non-invasive assessment of the CB2R availability by positron emission tomography (PET) revealed favourable binding properties and brain uptake, however rapid metabolism, and generation of brain-penetrating radiometabolites have been its main limitations. To reduce the bias of CB2R quantification by blood-brain barrier (BBB)-penetrating radiometabolites, we aimed to improve the metabolic stability by developing d4 and -d8 deuterated isotopologues of [18F]JHU94620. Experimental Approach: [18F]JHU94620-d8 was further evaluated to characterize its binding properties, metabolic stability, formation of BBB-penetrant radiometabolites and biodistribution in mice and rats. Key Results: The deuterated [18F]JHU94620 isotopologues showed improved metabolic stability avoiding the accumulation of BBB-penetrating radiometabolites in the brain over time. CB2R-specific binding with KD values in the low nanomolar range was determined across species. Dynamic PET studies revealed a CB2R-specific and reversible uptake of [18F]JHU94620-d8 in the spleen and to a local hCB2R(D80N) protein overexpression in the striatal region in rats. Conclusion and Implications: These results support further investigations of [18F]JHU94620-d8 in pathological models and tissues with a CB2R overexpression as a prerequisite for clinical translation.

Liquid-phase adsorption has hardly been established in micro-flow, although this constitutes an industrially vital method for product separation. A micro-flow UV-photo isomerization process converts cis-cyclooctene partly into trans-cyclooctene, leaving an isomeric mixture. Trans-cyclooctene adsorption and thus separation was achieved in a fixed-bed micro-flow reactor, packed with AgNO3/SiO2 powder, while the cis-isomer stays in the flow. The closed-loop recycling-flow has been presented as systemic approach to enrich the trans-cyclooctene from its cis-isomer. In-flow adsorption in recycling-mode has hardly been reported so that a full theoretical study has been conducted. This insight is used to evaluate three process design options to reach an optimum yield of trans-cyclooctene. These differ firstly in the variation of the individual residence times in the reactor and separator, the additional process option of refreshing the adsorption column under use, and the periodicity of the recycle flow.