Imaging histamine H3 receptors with [18 F]FMH3: Test-retest and occupancy studies in the non-human primate.

A positron emission tomography (PET) radioligand, [18 F]FMH3, has been developed to interrogate histamine receptor subtype 3 (H3R), where dysfunction at this site is linked with obesity, sleep abnormality, and cognitive disorders. [18 F]FMH3 was evaluated for imaging central H3R sites in non-human primates through test-retest (TRT) and dose-receptor occupancy studies with two selective H3R antagonists in order to support clinical investigations. Two adult female baboons underwent [18 F]FMH3 PET brain scans in the HR+, at repeated baseline (n = 7) and following administration of escalating doses of ABT-239 (0.003-0.1m/kg, n = 4) and ciproxifan (0.5-2.1 mg/kg, n = 7). Volume of distribution (VT ) in brain regions was estimated using the 2-tissue compartment model. TRT variability of VT across repeated baseline scans was reported as % coefficient of variation (COV). ABT-239 and ciproxifan occupancy at H3R was estimated using the occupancy plot, and the relationship of occupancy with dose and plasma levels was determined. In baboons, distribution of [18 F]FMH3 was high in the striatum, intermediate in cortical regions, and low in the brain stem. COV of baseline VT was 7.0 ± 3.5%, averaged across regions and animals. Dose-dependent effects of ABT-239 and ciproxifan measured the brain. ED50 and EC50, respectively, were 0.011 mg/kg and 0.942 ng/ml for ABT-239 and 0.73 mg/kg and 208.3 ng/ml for ciproxifan. [18 F]FMH3 demonstrated high TRT reliability and can be used to measure occupancy of H3R-targeted drugs. Validation in non-human primates support [18 F]FMH3 PET studies toward clinical investigations of H3R.

Sexually violent predator evaluations: empirical evidence, strategies for professionals, and research directions.

Several states have passed civil commitment laws that allow the precautionary detention of sex offenders who have completed their criminal sentences. Over 2,500 sex offenders have been committed across states with such statutes and several thousand more sex offenders have been evaluated. Most statutes call for an evaluation of risk by a mental health professional and, although each state statute is worded differently, three main elements common to sexually violent predator evaluations are used to guide evaluators: mental abnormality, volitional capacity, and likelihood of future sexual violence. The current article presents empirical evidence for the main tenants of these forensic evaluations, provides recommendations for evaluators in light of current limitations of evidence, and offers suggestions for future research in this area of forensic assessment.