The cuprizone (CPZ) mouse model for multiple sclerosis enables researchers to investigate the underlying mechanisms of demyelination and remyelination, as well as the effect of therapeutic interventions thereon. Over the last five decades, research revealed detailed analyses of brain tissue derived from CPZ-fed animals at different times of de- and re-myelination. Yet, longitudinal analysis of the effects of a CPZ diet on locomotor performance, myelination and neuroinflammation over a two-month recovery period are still unexplored. In this study, we comprehensively examined behavioural and neuropathological changes in the CPZ mouse model for a follow-up period of two months. We combined a longitudinal PET imaging approach with a more traditional approach of obtaining tissue and performing immunohistochemistry and behavioural tests in cohorts. We found that mice fed with 0.2% CPZ for 5weeks showed transient motor deficits which recovered quickly after cuprizone was removed from the diet. Similarly, remyelination also promptly restored myelin content after CPZ toxic insult, as seen by PET imaging with [11C]MeDAS and myelin histological staining. Remarkably, five weeks of CPZ feeding led to persistent glial activation, especially in the corpus callosum, for at least two months. This effect was measured both with [11C]PK11195 PET and with immunohistochemical staining for microglia and astrocytes. Taken together, this longitudinal study reveals that a five-week CPZ diet leads to transient motor and loss of myelin, which recover quickly after CPZ is removed. In contrast, neuroinflammation persists for at least two months following exposure and is mainly driven by astrocyte activation. The study warrants deeper analysis of the sustained neuroinflammatory response in the context of demyelinating diseases.

To compare the diagnostic performance of [18F]FDG and [18F]PSMA‑1007 PET/CT for detecting primary tumors, regional lymph node involvement, and distant metastases in recently diagnosed muscle‑invasive bladder cancer (MIBC). Prospective single‑center cohort of six patients (ages 57-82). Both PET/CTs were acquired within 30days under EANM/SNMMI-conformant protocols, with blinded consensus readings and post-diuretic pelvic acquisitions. [18F]PSMA‑1007 identified 15 lesions versus 14 with [18F]FDG. Primary bladder lesions were detected in 5 of 6 patients, compared to 3 of 6 patients. Both tracers detected nodal metastases in three patients and bone metastases in one. An [18F]FDG‑avid pulmonary lesion near the spleen was not detected with [18F]PSMA‑1007 owing to physiological splenic uptake. Both tracers showed comparable sensitivity for metastatic disease. The hepatobiliary clearance of [18F]PSMA‑1007 improved visualization of intravesical disease, supporting its use in staging and potential theranostic strategies in selected MIBC patients. Such real-world findings inform refinements for future study procedures, logistics, and methodological design, which are essential for minimizing research waste by identifying potential problems early. Not applicable.

Fallypride is a widely used high affinity radioligand for quantification of D2-dopamine receptor binding in small animal PET imaging. To examine the effect of mass both [18F]fallypride and [11C]fallypride was injected in mice over a wide range of molar activity and the binding potential (BP) was compared. Eight mice (C57BL/6J) went through three PET measurements within two weeks. [11C]fallypride with the highest possible molar activity (MA) and [18F]fallypride with normal and lower molar activity (lowerMA). The binding of [11C]fallypride was highest with a BPND of 13.5 ± 1.1 BPND. The binding of [18F]fallypride was lower, 8.6 ± 2.2 BPND in the normal condition and 5.3 ± 1.3 BPND at the lowerMA condition. By consequence, BPND showed a strong negative correlation with injected mass (R2 = 0.95, P < 0.05). Binding data were entered in a Scatchard analysis yielding a Bmax of 62pmol/g and a KD of 0.25nM. In this PET study in mice the average radioligand occupancy was estimated to 19% even for 11C-labeled fallypride despite the high MA of 153.3GBq/µmol and low injected mass of 0.03 µg. Therefore, high affinity radioligands should be applied with care in small animal PET studies and radiochemistry has to be at its best to assure that tracer conditions are met in small animal imaging PET imaging.