A facile synthesis of precursor for the σ-1 receptor PET radioligand [18 F]FTC-146 and its radiofluorination.

The σ-1 receptor is a non-opioid transmembrane protein involved in various human pathologies including neurodegenerative diseases, inflammation, and cancer. The previously published ligand [18 F]FTC-146 is among the most promising tools for σ-1 molecular imaging by positron emission tomography (PET), with a potential for application in clinical diagnostics and research. However, the published six- or four-step synthesis of the tosyl ester precursor for its radiosynthesis is complicated and time-consuming. Herein, we present a simple one-step precursor synthesis followed by a one-step fluorine-18 labeling procedure that streamlines the preparation of [18 F]FTC-146. Instead of a tosyl-based precursor, we developed a one-step synthesis of the precursor analog AM-16 containing a chloride leaving group for the SN 2 reaction with 18 F-fluoride. 18 F-fluorination of AM-16 led to a moderate decay-corrected radiochemical yield (RCY = 7.5%) with molar activity (Am ) of 45.9 GBq/µmol. Further optimization of this procedure should enable routine radiopharmaceutical production of this promising PET tracer.

From impact to recovery: tracking mild traumatic brain injury with MRI-a pilot study and case series.

Background: Diagnosis and recovery tracking of mild traumatic brain injury (mTBI) is often challenging due to the lack of clear findings on routine imaging techniques. This also complicates defining safe points for returning to activities. Hypothesis/purpose: Quantitative susceptibility mapping (QSM) can provide information about cerebral venous oxygen saturation (CSvO2) in the context of brain injury. We tested the prediction that these imaging modalities would enable the detection of changes and recovery patterns in the brains of patients with mTBI. Study design: In a case-control study, we recruited a cohort of 24 contact sport athletes for baseline QSM and resting-state functional MRI (rs-fMRI) scanning. Two of those who subsequently experienced head impact with significant post-injury symptoms underwent scans at 3, 7, 14 and 28 days post-injury; one had a boxing match without classical mTBI symptoms were also followed-up on. Results: The cohort baseline QSM measurements of the straight sinus were established. The two injured athletes with post-impact symptoms consistent with mTBI had susceptibility results at days 3 and 7 post-impact that fell below the 25th percentile of the baseline values. The per cent amplitude fluctuation quantified from rs-fMRI agreed with the susceptibility trends in the straight sinus. Conclusion: QSM holds promise as a diagnostic tool for tracking mTBI progression or recovery in contact sport head injury.

Diffusion tensor imaging and plasma immunological biomarker panel in a rat traumatic brain injury (TBI) model and in human clinical TBI.

Introduction: Neuroinflammatory reactions play a significant role in the pathology and long-term consequences of traumatic brain injury (TBI) and may mediate salutogenic processes that white matter integrity. This study aimed to investigate the relationship between inflammatory markers and white matter integrity following TBI in both a rat TBI model and clinical TBI cases. Methods: In the rat model, blood samples were collected following a controlled cortical impact (CCI) to assess a panel of inflammatory markers; MR-based diffusion tensor imaging (DTI) was employed to evaluate white matter integrity 60 days post-injury. 15 clinical TBI patients were similarly assessed for a panel of inflammatory markers and DTI post-intensive care unit discharge. Blood samples from healthy controls were used for comparison of the inflammatory markers. Results: Time-dependent elevations in immunological markers were observed in TBI rats, with a correlation to preserved fractional anisotropy (FA) in white matter. Specifically, TBI-induced increased plasma levels of IL-1ß, IL-6, G-CSF, CCL3, CCL5, and TNF-α were associated with higher white matter integrity, as measured by FA. Clinical cases had similar findings: elevated inflammatory markers (relative to controls) were associated with preservation of FA in vulnerable white matter regions. Discussion: Inflammatory markers in post-TBI plasma samples are ambivalent with respect to prediction of favourable outcome versus a progression to more pervasive pathology and morbidity.