Synthesis and biological evaluation of PET tracers designed for imaging of calcium activated potassium channel 3.1 (KCa3.1) channels in vivo

Expression of the Ca²⁺ activated potassium channel 3.1 (K_Ca3.1) channel (also known as the Gàrdos channel) is dysregulated in many tumor entities and has predictive power with respect to patient survival. Therefore, a positron emission tomography (PET) tracer targeting this ion channel could serve as a potential diagnostic tool by imaging the K_Ca3.1 channel in vivo. It was envisaged to synthesize [¹⁸F]senicapoc ([¹⁸F]1) since senicapoc (1) shows high affinity and excellent selectivity towards the K_Ca3.1 channels. Because problems occurred during ¹⁸F-fluorination, the [¹⁸F]fluoroethoxy senicapoc derivative [¹⁸F]28 was synthesized to generate an alternative PET tracer targeting the K_Ca3.1 channel. Inhibition of the K_Ca3.1 channel by 28 was confirmed by patch clamp experiments. In vitro stability in mouse and human serum was shown for 28. Furthermore, biodistribution experiments in wild type mice were performed. Since [¹⁸F]fluoride was detected in vivo after application of [¹⁸F]28, an in vitro metabolism study was conducted. A potential degradation route of fluoroethoxy derivatives in vivo was found which in general should be taken into account when designing new PET tracers for different targets with a [¹⁸F]fluoroethoxy moiety as well as when using the popular prosthetic group [¹⁸F]fluoroethyl tosylate for the alkylation of phenols.

Expression of the Ca²⁺ activated potassium channel 3.1 (K_Ca3.1) channel (also known as the Gàrdos channel) is dysregulated in many tumor entities and has predictive power with respect to patient survival.     

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long‐term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then consider the efficacy of bone marrow–derived mesenchymal stem/stromal cell (BM‐MSC) transplantation as a therapy for these injuries. Finally, we examine recent laboratory and clinical studies utilizing transplanted BM‐MSCs as antiinflammatory and neurorestorative treatments for stroke and TBI. Clinical trials of BM‐MSC transplants for stroke and TBI support their promising protective and regenerative properties. Future research is needed to allow for better comparison among trials and to elaborate on the emerging area of cell‐based combination treatments.     

A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres

Journal of Neurology - To identify the genetic cause of complex neuropathy in two siblings from a consanguineous family. The patients were recruited from our clinic. Muscle biopsy and whole-exome...