Imaging agents for nicotinic α4β2 receptors in the brain have been underway for studying various CNS disorders. Previous studies from our laboratories have reported the successful development of agonist, 18F-nifene. In attempts to develop potential antagonists, 18F-nifrolidine and 18F-nifzetidine were previously reported. Further optimization of these fluoropropyl derivatives has now been carried out resulting in 3-(2-(S)-3,4-dehydropyrrolinylmethoxy)-5-(3′-Fluoropropyl)pyridine (nifrolene) as a new high affinity agent for nicotinic α4β2 receptors. Nifrolene in rat brain homogenate assays—labeled with 3H-cytisine—exhibited a binding affinity of 0.36 nM. The fluorine-18 analog, 18F-nifrolene, was synthesized in approximately 10–20% yield and specific activity was estimated to be >2000 Ci/mmol. Rat brain slices indicated selective binding to anterior thalamic nuclei, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. This selective binding was displaced >90% by 300 µM nicotine. Thalamus to cerebellum ratio (>10) was the highest for 18F-nifrolene with several other regions showing selective binding. In vivo rat PET studies exhibited rapid uptake of 18F-nifrolene in the brain with specific retention in the thalamus and other brain regions while clearing out from the cerebellum. Thalamus to cerebellum ratio value in the rat was >4. Administration of nicotine caused a rapid decline in the thalamic 18F-nifrolene suggesting reversible binding to nicotinic receptors. PET imaging studies of 18F-nifrolene in anesthetized rhesus monkey revealed highest binding in the thalamus followed by regions of the lateral cingulated and temporal cortex. Cerebellum showed the least binding. Thalamus to cerebellum ratio in the monkey brain was >3 at 120 min. These ratios of 18F-nifrolene are higher than measured for 18F-nifrolidine and 18F-nifzetidine. 18F-Nifrolene thus shows promise as a new PET imaging agent for α4β2 nAChR.
Systemic lupus erythematosus (SLE) is an autoimmune disorder which can affect multiple organs and clinical presentation is often a myriad of symptoms; therefore, the index of suspicion should rise when evaluating patients with multiorgan symptomatology. Lupus enteritis is a distinct subset of SLE, defined as either vasculitis or inflammation of the small bowel, with supportive image and/or biopsy findings. The clinical picture of lupus enteritis is often nonspecific, with mild to severe abdominal pain, diarrhea, and vomiting being the cardinal manifestations. Although considered a form of visceral or serosal vasculitis, lupus enteritis is seldom confirmed on histology, making computerized tomography (CT) the gold standard for diagnosis. Lupus enteritis is generally steroid-responsive, and the route of administration is based on clinical status and organ involvement, with preference for intravenous (IV) route in flares with significant tissue edema. The following case describes a young woman presenting with lupus enteritis and lupus panniculitis as an initial manifestation of SLE, the utilization of abdominal CT in diagnosis, and current treatment protocols used for lupus enteritis.
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