Automated radiosynthesis and clinical experience of [<sup>18</sup>F]SMBT-1 PET imaging for <i>in vivo</i> evaluation of reactive astrocyte in Parkinson's disease: a pilot study.

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BackgroundNeuroinflammation plays an important role in progression of Parkinson disease (PD). [18F]SMBT-1 is a promising novel radiotracer for in vivo evaluation of reactive astrogliosis.MethodsThe automated radiosynthesis of [18F]SMBT-1 was optimized and performed production by using the Synthra RNplus synthesizer module, and the quality of the labeled tracer was evaluated. Total 5 participants, 2 PD and 3 Healthy Control were enrolled. Cognitive assessments were performed in all participants while H&Y scales and MDS-UPDRS were performed only in PD. All participants underwent [18F]SMBT-1 PET/MRI and [18F]FDOPA PET/CT within 2-week intervals. Demographic and imaging data were collected. The correlation between [18F]FDOPA uptake and [18F]SMBT-1 uptake was analyzed by Spearman's correlation.Results[18F]SMBT-1 was successfully synthesized via nucleophilic substitution of a tosylate precursor, followed by a deprotection step. After purification and formulation, [18F]SMBT-1 was obtained with an average decay-corrected radiochemical yield of 36.56 ± 11.55% and molar activity as 396 Gbq/μmol at the end of synthesis (n = 7). Moderate PD defined by the [18F]FDOPA showed increased [18F]SMBT-1 in prefrontal cortex, temporal lobes, striatum, thalamus, pons, medullar, and midbrain while severe PD showed globally increased [1⁸F]SMBT-1. Healthy control also showed globally increased [18F]SMBT-1 uptake. There was no significant correlation between the degree of [18F]FDOPA uptake and [18F]SMBT-1 uptake in any brain region.ConclusionThe automated radiosynthesis of [18F]SMBT-1 are suitable for routine production without any immediate complication reported after administration. Moderate PD shows decreased astrocyte function as they lose neuroprotective astrocytes while severe PD shows increased astrocyte function as increased neurotoxic astrocytes.

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