Microtubule (MT) dysfunction is a hallmark of neurodegenerative diseases, tauopathies, and genetic disorders. Positron emission tomography (PET) enables non-invasive assessment of MT dynamics in vivo, but current ¹¹C-labeled radiotracers are limited by the short half-life of carbon-11. Here, we report the radiosynthesis and in vitro evaluation of [¹⁸F]FE-MPC6827, an ¹⁸F-labeled derivative of the brain-penetrant MT-destabilizing agent MPC-6827 (verubulin). Radiosynthesis from the corresponding tosylate precursor afforded [¹⁸F]FE-MPC6827 in 60±3% radiochemical yields (n=22), >99% radiochemical purities, and molar activities up to 475 GBq/µmol. Physicochemical profiling revealed a logD_7.4 value of 3.37±0.05 and favorable CNS-MPO, BBB, and CNS-PET-MPO scores, indicating suitable properties for brain imaging. In HEK293T cells, MT destabilization significantly increased tracer accumulation, whereas MT stabilization significantly reduced uptake. Overexpression of MT-associated proteins (TAU, SPASTIN, MARK, α-tubulin) produced directionally consistent but statistically non-significant changes in tracer uptake concordant with effects on MT mass or stability. Across experiments, tracer uptake correlated inversely with MT stability. These findings suggest that [¹⁸F]FE-MPC6827 preferentially binds to depolymerized tubulin and responds to global shifts in MT dynamics, but may be less sensitive to subtle or localized cytoskeletal changes. Taken together, [¹⁸F]FE-MPC6827 is a promising first-in-class radiofluorinated PET tracer for imaging MT dynamics in the central nervous system.

Tryptophan (Trp) is the precursor for serotonin synthesis and other biologically relevant metabolites. We evaluated the novel radiotracer 7-[ ¹⁸ F]Fluorotryptophan (7-[ ¹⁸ F]FTrp) to assess its biodistribution, dosimetry, and potential for imaging brain Trp metabolism in humans. Six healthy volunteers underwent whole-body PET/CT imaging over 5.5 hours following intravenous injection of 7-[ ¹⁸ F]FTrp. An additional four subjects underwent dynamic brain PET imaging for 2 hours. Time-activity curves (TACs) were extracted for source organs using VOIs defined on co-registered CT and PET images, and dosimetry was calculated using OLINDA software. The radiotracer showed rapid uptake and distribution, with highest activity observed in the liver, pancreas, salivary glands, in combination with urinary excretion. Brain pharmacokinetic analyses with image-derived input function (IDIF) determined that Patlak analyses were the best fit for brain image analyses. Brain uptake was modest, with highest region-specific accumulation in the pineal gland, which is a known site for serotonin synthesis. The estimated effective dose was within the expected range for ¹⁸ F-labeled compounds (14.1 ± 0.2 μSv/MBq). Our findings indicate that 7-[ ¹⁸ F]FTrp is safe for human use, demonstrates favorable kinetics for studying both brain and peripheral Trp metabolism, and warrants further exploration in patients with serotonin metabolism disorders.