Methods: Radiolabeling of the peptides Selumetinib was effected by ligancl exchange from Tc-99m-glucoheptonate, and the desired products were purified by radio-RP-HPLC. The in vitro stability in phosphate buffered saline, mouse serum and cysteine solutions at physiological temperature and pH for all seven Tc-99m-cyclized peptides was determined by radio-RP-HPLC and radio-TLC. Normal CF-1 mouse biodistribution studies were performed for three of the Tc-99m-cyclized peptides.
Results: Based on the fully characterized Re-cyclized peptide analogues, four Tc-99m-coordination motifs were proposed for the Tc-99m-cyclized peptides. Technetium-99m-cyclized Tyr(3)-octreotate
derivatives with N2S2 metal coordination modes and large metal ring sizes were susceptible to oxidation and loss of Tc-99m in the form of (TcO4-)-Tc-99m, as evidenced by their instability in the various solutions under physiological conditions (15-58% intact at 24 h). As anticipated, the addition of a third cysteine to the sequence stabilized the Tc-99m metal
coordination, and peptides with NS3 coordination modes remained >85% intact out to 24 h. No significant differences were observed in the biodistribution studies performed with three peptides of varying stabilities.
Conclusions: Improvements in stability were not sufficient to outweigh the low somatostatin receptor affinity for the peptides in this study. BTSA1 Further
improvements in the peptide sequence and/or metal coordination are needed to result in a radiodiagnostic/radiotherapeutic pair for targeting the somatostatin receptor. (C) 2011 Elsevier Inc. All rights reserved.”
“Objective: Myocardial infarction leads to contractile dysfunction. In patients with diabetes, impaired contractility has been Dynein associated with the loss of insulin effects and mitochondrial dysfunction. We assessed cardiac insulin sensitivity and mitochondrial and contractile function in rats after ligation of the left coronary artery.
Methods: At 2 weeks after left coronary artery ligation, we performed echocardiography in vivo and assessed the substrate use and insulin response in the isolated working heart and the regulation of insulin (Akt, glucose transporter type 4) and mitochondrial signaling (p38 mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, mitochondrial transcription factor A) using polymerase chain reaction and Western blotting.
Results: The infarcted hearts were dilated and had a reduced ejection fraction (ejection fraction < 50%). The basal glucose oxidation was preserved, but the fatty acid oxidation was significantly reduced. Insulin’s effect on substrate oxidation was significantly impaired for both the decrease in fatty acid oxidation and the increase in glucose oxidation.