134 Objectives The failing human heart is related with a selective reduction in β1-adrenoceptor. We designed radiolabeled esmolol, is known to be a cardioselective β1 receptor blocker in the sympathetic nervous system. A new 99mTc-labeld esmolol derivative (99mTc-EDA-ESM) was prepared and its binding and biokinetic characteristics in normal rat for the noninvasive measurement of cardiac β1-adrenoceptor density. Methods 99mTc-EDA-ESM was prepared by reacting 99mTcO4- with the precursor in the presence of SnF2, ascorbic acid, and mannitol at room temperature for 30 sec. To optimize the labeling condition, a variety of attempts were investigated with different reducing agents and anti-oxidants. For assessment of heart and major organ uptake of radiotracer, serial SPECT/CT images of 99mTc-EDA-ESM (74 MBq) in normal rat were obtained in 12 projections over a 10-min period and blocking experiment was performed with esmolol or atenolol. Results 99mTc-EDA-ESM was synthesized in 95% radiochemical yield with over 98% of radiochemical purity. Mass and NMR data of Re-EDA-ESM were used for the speculation of 99mTc-EDA-ESM structure. In serial SPECT images, radiotracer showed high accumulation in the heart and kidneys, while radio-uptake was relatively low in the liver and lung. ROIs were drawn in the lung, the liver and the heart, and their radioactivity were shown as 0.38±0.04, 1.10±0.20, and 1.88±0.20%ID/g at 5 min post-injection and 0.21±0.03, 0.85±0.22, and 1.02±0.15%ID/g at 25 min post-injection, respectively. In vivo blocking with excess esmolol or atenolol resulted in significantly reduced radioactivity uptake in the heart by 92% and 76%, respectively. Conclusions Our results demonstrate that 99mTc-EDA-ESM exhibits specific β1-adrenergic receptor binding and favorable in vivo biokinetic characteristics, making it a promising SPECT radiotracer for the imaging of β1-adrenoceptors.
The intervertebral disc (IVD) is a complex joint structure comprising three primary components—namely, nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP). The IVD retrieves oxygen from the surrounding vertebral body through CEP by diffusion and likely generates ATP via anaerobic glycolysis. IVD degeneration is characterized by a cascade of cellular, compositional, structural changes. With advanced age, pronounced changes occur in the composition of the disc extracellular matrix (ECM). NP and AF cells in the IVD possess poor regenerative capacity compared with that of other tissues. Hypoxia-inducible factor (HIF) is a master transcription factor that initiates a coordinated cellular cascade in response to a low oxygen tension environment, including the regulation of numerous enzymes in response to hypoxia. HIF-1α is essential for NP development and homeostasis and is involved in various processes of IVD degeneration process, promotes ECM in NP, maintains the metabolic activities of NP, and regulates dystrophic mineralization of NP, as well as angiogenesis, autophagy, and apoptosis during IVD degeneration. HIF-1α may, therefore, represent a diagnostic tool for early IVD degeneration and a therapeutic target for inhibiting IVD degeneration
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