Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-T807, which may be useful for imaging Alzheimer's disease and other tauopathies. Here in, we describe the first human brain images with [F-18]-T807.

IntroductionThe Biosimilars Forum conducted a survey through an independent organization from November 20, 2015 to January 4, 2016 in order to assess current levels of awareness, knowledge, and perceptions of biosimilars among US specialty physicians who already prescribe biologics. The survey was intended to provide a baseline level of knowledge about biosimilars and will be repeated in 2–3 years in order to monitor trends over time.MethodsA 19-question survey was created by the Biosimilars Forum and was administered by an independent third party.ResultsResponses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including dermatologists, gastroenterologists, hematologist-oncologists, medical oncologists, nephrologists, and rheumatologists.ConclusionsThe results of this survey highlight a significant need for evidence-based education about biosimilars for physicians across specialties. Five major knowledge gaps were identified: defining biologics, biosimilars, and biosimilarity; understanding the approval process and the use of “totality of evidence” to evaluate biosimilars; understanding that the safety and immunogenicity of a biosimilar are comparable to the originator biologic; understanding the rationale for extrapolation of indications; and defining interchangeability and the related rules regarding pharmacy-level substitution. Funding: Biosimilars Forum.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0431-5) contains supplementary material, which is available to authorized users.

Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have recently reported early clinical results of a novel PHF-tau targeting PET imaging agent, [F18]-T807. Since then, we have investigated a second novel PHF-tau targeting PET imaging agent, [F18]-T808, with different pharmacokinetic characteristics, which may be favorable for imaging Alzheimer's disease and other tauopathies. Here, we describe the first human brain images with [F18]-T808.

Standardized uptake value (SUV) normalized by lean body mass ([LBM] SUL) is becoming a popular metric for quantitative assessment of clinical PET. Sex-specific quantitative effects of different LBM formulations on liver SUV have not been well studied. Methods 18F-FDG PET/CT scans from 1,033 consecutive adult (501 women, 532 men) studies were reviewed. Liver SUV was measured with a 3-cm-diameter spheric region of interest in the right hepatic lobe and corrected for LBM using the sex-specific James and Janmahasatian formulations. Results Body weight was 71.0 ± 20.7 kg (range, 18.0–175.0 kg) and 82.9 ± 18.6 kg (range, 23.0–159.0 kg) for women and men, respectively. SUV, based on body weight, has a significantly positive correlation with weight for both women (r = 0.58, P < 0.0001) and men (r = 0.54, P < 0.0001). This correlation is reduced in men (r = 0.11, P = 0.01) and becomes negative for women (r = −0.35, P = 0.0001) with the James formulation of SUL. This negative correlation was eliminated when the very obese women (body mass index ≥ 35) were excluded from the analysis (r = 0.13, P = 0.8). The Janmahasatian formulation annuls the correlation between SUL and weight for women (r = 0.04, P = 0.4) and decreases it for men (r = 0.13, P = 0.003). Conclusion Hepatic correction with the more common James formulation for body lean mass breaks down and shows low SUL values in very obese patients. The adoption of the Janmahasatian formula for estimation of LBM in modern PET scanners and display workstations is recommended, in view of the increasing frequency of obesity.

Venetoclax is a selective, first-in-class, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in several hematological malignancies. Two studies evaluated the relative bioavailability of venetoclax in healthy subjects: (1) a bioequivalence study to compare the bioavailability of the film-coated tablet with that of an earlier uncoated tablet and (2) a food effect study to evaluate the effect of food on venetoclax pharmacokinetics. Both studies were open-label, single-dose, crossover studies. In the bioequivalence study, 15 subjects received a single dose of venetoclax 50 mg under nonfasting conditions, in each of 2 periods; one period used the uncoated tablet, and the other used the film-coated tablet. In the food effect study, 24 subjects received a single dose of venetoclax film-coated 100-mg tablet under fasting conditions, after a low-fat breakfast or after a high-fat breakfast in different periods. The venetoclax film-coated tablet was bioequivalent to the uncoated tablet, which indicates that the film coating does not affect bioavailability. The median T of venetoclax was delayed by about 2 hours when administered with food. Compared with fasting conditions, C and AUC increased by approximately 3.4-fold following a low-fat breakfast. High-fat meals increased C and AUC by approximately 50% relative to low-fat meals. The mean terminal half-life was comparable between the high-fat meal and fasting conditions (19.1 versus 16.1 hours). Based on these results and the venetoclax exposure-response profile, venetoclax should be administered with food and without specific recommendations for fat content to ensure adequate and consistent bioavailability.