In vivo imaging of β-amyloid plaques in the brain may lead to the early diagnosis of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. In the present study, we report on the development of two potential PET probes, [(18)F]FPYBF-2 ([(18)F]10) and [(18)F]FPHBF-2 ([(18)F]21), for imaging of β-amyloid plaques in AD brain. In experiments in vitro, 10 and 21 displayed high affinity for Aβ(1-42) aggregates (K(i) = 2.41 and 3.85 nM, respectively). In biodistribution experiments using normal mice, they displayed high uptake in the brain (7.38 and 8.18% ID/g at 2 min postinjection, respectively), and the radioactivity washed out from the brain rapidly (3.15 and 3.87% ID/g at 60 min postinjection, respectively), which is highly desirable for β-amyloid imaging agents. In vivo, they clearly labeled β-amyloid plaques in Tg2576 mice. Furthermore, the specific labeling of β-amyloid plaques by 10 and 21 was observed in autoradiographs of sections of autopsied AD brain. These new fluorinated benzofuran derivatives are promising PET probes for imaging cerebral β-amyloid plaques.

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Three novel (99m)Tc-labeled pyridyl benzofuran derivatives were tested as potential probes for imaging β-amyloid plaques using single photon emission computed tomography (SPECT). The (99m)Tc and corresponding rhenium complexes were synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. All Re complexes showed affinity for Aβ(1-42) aggregates (K(i) = 13.6-149.6 nM). Biodistribution experiments in normal mice revealed that the (99m)Tc-labeled derivatives displayed sufficient uptake in the brain (1.41-1.80% ID/g at 2 min postinjection). Notably, [(99m)Tc]BAT-Bp-2 showed a good initial uptake (1.80% ID/g at 2 min) and a reasonable washout from the brain (0.79% ID/g at 60 min). Ex vivo autoradiography with [(99m)Tc]BAT-Bp-2 revealed substantial labeling of β-amyloid plaques in sections of brain tissue from Tg2576 transgenic mice but not in the age-matched controls. [(99m)Tc]BAT-Bp-2 may be a potential SPECT probe for imaging β-amyloid plaques in Alzheimer's brains.

Objective Our study aims to assay the irisin level and investigate the relationships of irisin level with body mass index (BMI), body composition and bone metabolism in the polycystic ovary syndrome (PCOS) and control women.Methods Fifty two PCOS and 39 control women were recruited. Serum sex hormone, fasting insulin and C-peptide were tested. Fasting serum irisin and adiponectin were measured with enzyme-linked immunosorbent assay. Body composition and bone mineral density were assayed by dual energy X-ray absorptiometry.Results Polycystic ovary syndrome women showed different body compositions compared with controls. Serum irisin level of PCOS did not show significant difference compared with controls although it was decreased. The level of adiponectin in PCOS patients was significantly reduced. BMI had no correlation with irisin level. It indicated a positive correlation between serum irisin levels and bone mineral density in the control group and a negative correlation in the PCOS group after BMI and age adjusted. Furthermore, total lean mass has a significant effect on irisin concentration in the PCOS group. There are no correlations between adiponection and body compositions and bone mineral density in both groups.Conclusions The abnormal body composition in PCOS may contribute to the circulation irisin. The crosstalk of irisin in different organs was found and may be related to disease development in PCOS.

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This paper describes the synthesis and biological evaluation of fluoro-pegylated (FPEG) chalcones for the imaging of beta-amyloid (Abeta) plaques in patients with Alzheimer's disease (AD). FPEG chalcone derivatives were prepared by the aldol condensation reaction. In binding experiments conducted in vitro using Abeta(1-42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed higher Ki values (20-50 nM) than those having a monomethylamino or a primary amine group. When the biodistribution of 11C-labeled FPEG chalcone derivatives having a dimethyamino group was examined in normal mice, all four derivatives were found to display sufficient uptake for imaging Abeta plaques in the brain. 18F-labeled 7c also showed good uptake by and clearance from the brain, although a slight difference between the 11C and 18F tracers was observed. When the labeling of Abeta plaques was carried out using brain sections of AD model mice and an AD patient, the FPEG chalcone derivative 7c intensely labeled Abeta plaques. Taken together, the results suggest 7c to be a useful candidate PET tracer for detecting Abeta plaques in the brain of patients with AD.

In vivo detection of cerebral β-amyloid fibrils may facilitate the monitoring of β-amyloidosis in the brain and effectiveness of antiamyloid therapies. Thioflavin T (ThT) is a widely used dye for the spectroscopic determination of β-amyloid fibrils, but its ability to detect cerebral β-amyloid fibrils in vivo is limited due to the charged molecule. To this end, a smart dicynomethylene-4H-pyran (DCM) fluorophore, namely, (E)-2-(2-(4-(dimethylamino)styryl)-6-methyl-4H-pyran-4-ylidene) malononitrile (PAD-1), was evaluated for in vivo fluorescence imaging of cerebral β-amyloid fibrils. PAD-1 rapidly entered the brain with high initial brain uptake after intravenous injection, which is highly desirable for in vivo detection of β-amyloid fibrils. PAD-1 displayed a turn-on effect, showing significant enhancement in fluorescence when bound to the aggregated β-amyloid fibrils. It also showed specific labeling of β-amyloid deposits in APP/PS1 transgenic mouse brains. Thus, PAD-1 proved to be a valuable alternative to ThT for cerebral β-amyloid detection and may enable quantitative imaging in vivo.

Imaging of β-amyloid (Aβ) plaques in the brain may facilitate the diagnosis of cerebral β-amyloidosis, risk prediction of Alzheimer’s disease (AD), and effectiveness of anti-amyloid therapies. The purpose of this study was to evaluate novel 123I-labeled pyridyl benzofuran derivatives as SPECT probes for Aβ imaging. The formation of a pyridyl benzofuran backbone was accomplished by Suzuki coupling. [123I/125I]-labeled pyridyl benzofuran derivatives were readily prepared by an iododestannylation reaction. In vitro Aβ binding assays were carried out using Aβ(1–42) aggregates and postmortem human brain sections. Biodistribution experiments were conducted in normal mice at 2, 10, 30, and 60 min postinjection. Aβ labeling in vivo was evaluated by small-animal SPECT/CT in Tg2576 transgenic mice injected with [123I]8. Ex vivo autoradiography of the brain sections was performed after SPECT/CT. Iodinated pyridyl benzofuran derivatives showed excellent affinity for Aβ(1–42) aggregates (2.4 to 10.3 nM) and intensely labeled Aβ plaques in autoradiographs of postmortem AD brain sections. In biodistribution experiments using normal mice, all these derivatives displayed high initial uptake (4.03–5.49% ID/g at 10 min). [125I]8 displayed the quickest clearance from the brain (1.30% ID/g at 60 min). SPECT/CT with [123I]8 revealed higher uptake of radioactivity in the Tg2576 mouse brain than the wild-type mouse brain. Ex vivo autoradiography showed in vivo binding of [123I]8 to Aβ plaques in the Tg2576 mouse brain. These combined results warrant further investigation of [123I]8 as a SPECT imaging agent for visualizing Aβ plaques in the AD brain.