A Fast-Binding, Functionally Reversible, COX-2 Radiotracer for CNS PET Imaging.

Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In the central nervous system (CNS), COX-2 is implicated in neurodegenerative and psychiatric disorders as a potential therapeutic target and biomarker. However, clinical studies with COX-2 have yielded inconsistent results, partly due to limited mechanistic understanding of how COX-2 activity relates to CNS pathology. Therefore, developing COX-2 positron emission tomography (PET) radiotracers for human neuroimaging is of interest. This study introduces [11C]BRD1158, which is a potent and uniquely fast-binding, selective COX-2 PET radiotracer. [11C]BRD1158 was developed by prioritizing potency at COX-2, isoform selectivity over COX-1, fast binding kinetics, and free fraction in the brain. Evaluated through in vivo PET neuroimaging in rodent models with human COX-2 overexpression, [11C]BRD1158 demonstrated high brain uptake, fast target-engagement, functional reversibility, and excellent specific binding, which is advantageous for human imaging applications. Lastly, post-mortem samples from Huntington's disease (HD) patients and preclinical HD mouse models showed that COX-2 levels were elevated specifically in disease-affected brain regions, primarily from increased expression in microglia. These findings indicate that COX-2 holds promise as a novel clinical marker of HD onset and progression, one of many potential applications of [11C]BRD1158 human PET.

Review of interventions that improve uptake of lung cancer screening: a cataloging of strategies that have been shown to work (or not).

TOPIC OF IMPORTANCE: Lung cancer screening (LCS) has the potential to decrease mortality from lung cancer by 20%. Yet, more than a decade since LCS was established as an evidence-based practice, < 20% of the eligible population in the US has been screened. This review focuses on critically appraising interventions that have been designed to increase the initial uptake of LCS, including how they address known barriers to LCS and their effectiveness in overcoming these barriers. REVIEW FINDINGS: Studies were categorized based on the primary barriers which they addressed: 1) identifying eligible patients (including enhancing awareness through smoking history collection, outreach, and education), 2) SDM-related interventions, and 3) patient navigation interventions. Four of the studies included multi-component interventions, which often included patient navigation as one of the components. Overall, the effectiveness of the studies reviewed at improving LCS uptake was generally modest and was limited by the multi-level barriers that need to be overcome. Multi-component interventions were generally more effective at improving LCS uptake but most studies still had relatively low completion of screening. SUMMARY: Improving uptake of LCS requires learning from prior interventions to design multi-level interventions that address barriers to LCS at key steps and identifying which components of these interventions are effective and generalizable.

Radiocaine: An Imaging Marker of Neuropathic Injury.

Voltage-gated sodium channels (Navs) play a crucial electrical signaling role in neurons. Nav-isoforms present in peripheral sensory neurons and dorsal root ganglia of the spinal cord are critically involved in pain perception and transmission. While these isoforms, particularly Nav1.7, are implicated in neuropathic pain disorders, changes in the functional state and expression levels of these channels have not been extensively studied in vivo. Radiocaine, a fluorine-18 radiotracer based on the local anesthetic lidocaine, a non-selective Nav blocker, has previously been used for cardiac Nav1.5 imaging using positron-emission tomography (PET). In the present study, we used Radiocaine to visualize changes in neuronal Nav expression after neuropathic injury. In rats that underwent unilateral spinal nerve ligation, PET/MR imaging demonstrated significantly higher uptake of Radiocaine into the injured sciatic nerve, as compared to the uninjured sciatic nerve, for up to 32 days post-surgery. Radiocaine, due to its high translational potential, may serve as a novel diagnostic tool for neuropathic pain conditions using PET imaging.