Novel Radioiodinated Aurones as Probes for SPECT Imaging of β-Amyloid Plaques in the Brain

We report a novel series of radioiodinated aurone derivatives as probes for imaging Aβ plaques in the brains of patients with Alzheimer’s disease (AD) using single photon emission computed tomography (SPECT). In binding experiments in vitro, aurone derivatives showed very good affinity for Aβ aggregates (Ki = 1.1 to 3.4 nM). No-carrier-added radioiodinated aurones were successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives. In biodistribution experiments using normal mice, aurone derivatives displayed high brain uptake (1.7−4.5% ID/g at 2 min) and rapid clearance from the brain (0.1−0.4% ID/g at 30 min), especially [125I]15. Furthermore, a specific plaque labeling signal was observed in in vitro autoradiography of postmortem AD brain sections using [125I]15. [125I]15 may be a useful SPECT imaging agent for detecting Aβ plaques in the brain of AD

Activation of brown adipose tissue in hypothyroidism

<div><p></p><p><b>Background</b> Brown adipose tissue (BAT) attracts growing interest as a potential therapeutic target for obesity and diabetes. Hyperthyroidism is well-known to increase BAT activity, but the role of hypothyroidism is controversial. We aimed to investigate the association between different thyroid hormone (TH) states and BAT activity.</p><p><b>Methods</b> FDG-PET studies were retrospectively evaluated in thyroid cancer patients after total thyroidectomy both at euthyroidism during TH replacement or at hypothyroidism after TH cessation. Serum TH levels were compared between patients with active BAT and control patients with non-active BAT matched for age, gender, and body mass index. Additionally, animal experiments with controls (<i>n</i> = 5) and hypothyroid rats (<i>n</i> = 5) were performed.</p><p><b>Results</b> Out of 124 patients, 6 patients with active BAT were identified. These patients showed significantly higher thyroid-stimulating hormone (TSH) levels than matched controls (<i>P</i> < 0.05). In animal experiments, all hypothyroid animals showed BAT activation at room temperature (24 °C), whereas controls did not (<i>P</i> < 0.001). Increased BAT activity was also confirmed by increased expression of UCP-1 and D2.</p><p><b>Conclusions</b> Increased BAT metabolism appears to be related with hypothyroidism, which might be the result of a feedback mechanism to maintain body temperature in a state of reduced basal thermogenesis. Future research needs to explore the underlying mechanistic and biological implications.</p><p></p><p>Key Messages</p><p></p><p>Increased brown adipose tissue (BAT) metabolism appears to be related with hypothyroidism, which might be the result of a feedback mechanism to maintain body core temperature in a state of reduced basal thermogenesis.</p><p></p><p></p><p></p></div

Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β‑Amyloid in Alzheimer’s Disease Affected Brain

In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo­[1,2-<i>a</i>]­pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of β-amyloid (Aβ). Among the 11 evaluated compounds, 10 showed moderate affinity to Aβ(1–42) aggregates, exhibiting half-maximal inhibitory concentrations (IC₅₀) of 14.7 ± 6.07–87.6 ± 39.8 nM. In vitro autoradiography indicated that ¹²³I-labeled triazole-substituted derivatives displayed highly selective binding to Aβ plaques in the hippocampal region of Alzheimer’s disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all ¹²³I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aβ plaques, with the highest selectivity observed for a 1<i>H</i>-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [¹²³I]­ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings