[(18)F]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD.

Senile plaques and neurofibrillary tangles are prominent neuropathological hallmarks in Alzheimer's disease and are considered to be targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. While there are a number of amyloid-β positron emission tomography (PET) tracers currently in different stages of clinical development and commercialization, there have been very few reports on imaging agents selectively targeting tau aggregates. In search of [18F]-PET tracers that possess great binding affinity and selectivity toward tau tangles, we tested more than 900 compounds utilizing a unique screening process. A competitive autoradiography assay was set up to test compounds for binding to native tau tangles and amyloid-β plaques on human brain tissue sections. In our in vitro assays, the 18F labeled compound [18F]-T808 displayed a high level of binding affinity and good selectivity for tau aggregates over amyloid-β plaques. [18F]-T808 showed rapid uptake and washout in rodent brains. Our in vitro and preclinical in vivo studies suggest that [18F]-T808 possesses suitable properties and characteristics to be a specific and selective PET probe for imaging of paired helical filament tau in human brains.

Purpose: Among derivatives of a-vitamin E, a-vitamin E succinate (VES), has attracted much attention due to its potent anti^prostate cancer activity in vitro and in vivo. However, the in vivo antitumor activity of VES might be compromised if administrated orally due to the VES hydrolysis by esterases in the gastrointestinal tract. Experimental Design: New nonhydrolyzable VES ether analogues were synthesized and their growth inhibition was screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide growth assay. Among them, RRR-a-tocopheryloxybutyl sulfonic acid (VEBSA) was further characterized by terminal deoxyribonucleotidyl transferase^mediated dUTP nick end labeling apoptosis assay, soft agar assay, and in vivo tumor formation. Results: VEBSA has potent antitumor ability, albeit to a lesser extent thanVES, in in vitro cultured prostate cancer LNCaP and PC3 cells. Like VES,VEBSA induced apoptosis, repressed androgen receptor protein expression, and enhanced vitamin D receptor expression, suggesting thatVEBSA can go through mechanisms similar to those used byVES to inhibit the growth of prostate cancer cells in vitro. However, 6 weeks of oral consumption ofVEBSA, but not ofVES, reduced the tumor burden in the xenografted prostate tumors in nude mice. Furthermore, oral intake of VEBSA for 20 weeks inhibited prostate tumor growth and progression more efficiently compared with VES in the prostate cancer tumor model of TRAMP mice. Conclusion: Oral consumption of VEBSA allows a greater anticancer activity compared with VES. Chemoprevention prefers the oral consumption of agents; the advantage of VEBSA over VES to be administrated orally will allow VEBSA to serve as an agent for both preventive and therapeutic purposes for prostate cancer.Growing lines of evidence suggest that VES is one of the most potent a-vitamin E analogues in terms of antiproliferative activity, and the underlying mechanisms in different cancer cells have been proposed (1 -8). Importantly, VES selectively inhibits the growth of cancer cells without affecting normal cells. This has been shown in cultured cells and animal models (3, 9 -11). However, the efficacy of VES in mouse cancer models requires VES to be delivered by i.p. administration, not by oral gavage (12), suggesting that i.v. application is required for VES to inhibit tumor growth in humans. Therefore, VES might be inconvenient for chemopreventive or therapeutic purposes. It is hypothesized that the low efficacy of VES by oral intake might be due to low bioavailability of VES, possibly caused by the presence of esterases in the gastrointestinal tract, which hydrolyze VES to a-vitamin E and succinic acid, which do not have antiproliferative activity on cancer cells. To validate whether low bioavailability is the cause of the low efficacy of VES administrated orally, we measured and calculated the tissue concentrations of VES in mice after either oral gavage or i.p. administration. Although twice as much VES was administered by oral gavage compared with i.p. admin...

BACKGROUND Polymorphic Light Eruption (PMLE) is the most common, recurrent idiopathic acquired photodermatosis with female preponderance. (1) Polymorphic light eruption has been found to be associated with thyroid function abnormalities. Aim-To study the clinico-epidemiological profile of polymorphic light eruptions and its association with thyroid function abnormalities. MATERIALS AND METHODS A prospective observational study was conducted for a period of one year from April 2017 to October 2017 in 50 patients presenting to the Outpatient Department with polymorphic light eruptions. Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (FT3) and Free Tetraiodothyronine (FT4) were estimated in these patients. Inclusion criterion was patients clinically diagnosed as cases of polymorphic light eruptions. Exclusion criteria were pregnancy, lupus erythematosus, inflammatory photodermatoses, use of drugs causing photosensitivity, specific treatment of polymorphic light eruption in last 3 months. RESULTS The study showed a female preponderance (68%). The average age at presentation was 30-35 yrs. Thyroid Function Tests (TFT) showed abnormality in 40% of cases. CONCLUSION This study showed that hypothyroidism has significant association with PMLE. (2) Cases of polymorphic light eruptions should be examined clinically for thyroid disorder and also tested for TFT and thyroid autoantibodies to find any association and prevent serious consequences.