Synthesis and Biological Evaluation of Iodoglucoazomycin (I‐GAZ), an Azomycin–Glucose Adduct with Putative Applications in Diagnostic Imaging and Radiotherapy of Hypoxic Tumors

Abstract

Iodoglucoazomycin (I‐GAZ; N‐(2‐iodo‐3‐(6‐O‐glucosyl)propyl)‐2‐nitroimidazole), a non‐glycosidic nitroimidazole–6‐O‐glucose adduct, was synthesized, radioiodinated, and evaluated as a substrate of glucose transporter 1 (GLUT1) for radiotheranostic (therapy+diagnostic) management of hypoxic tumors. Nucleophilic iodination of the nosylate synthon of I‐GAZ followed by deprotection afforded I‐GAZ in 74 % overall yield. I‐GAZ was radioiodinated via ‘exchange’ labeling using [123/131I]iodide (50–70 % RCY) and then purified by Sep‐Pak™ (>96 % RCP). [131I]I‐GAZ was stable in 2 % ethanolic solution in sterile water for 14 days when stored at 5 °C. In cell culture, I‐GAZ was found to be nontoxic to EMT‐6 cells at concentrations <0.5 mm, and weakly radiosensitizing (SER 1.1 at 10 % survival of EMT‐6 cells; 1.2 at 0.1 % survival in MCF‐7 cells). The hypoxic/normoxic uptake ratio of [123I]I‐GAZ in EMT‐6 cells was 1.46 at 2 h, and under normoxic conditions the uptake of [123I]I‐GAZ by EMT‐6 cells was unaltered in the presence of 5 mm glucose. The biodistribution of [131I]I‐GAZ in EMT‐6 tumor‐bearing Balb/c mice demonstrated rapid clearance from blood and extensive renal and hepatic excretion. Tumor/blood and tumor/muscle ratios reached ∼3 and 8, respectively, at 4 h post‐injection. Regression analysis of the first order polynomial plots of the blood and tumor radioactivity concentrations supported a perfusion–excretion model with low hypoxia‐dependent binding. [131I]I‐GAZ was found to be stable in vivo, and did not deiodinate.

Prevalence of Hypertension and Prognosis of Associated Dysfunction on Specific Organ Function among Ghanaian Adolescent Students

“…This prevalence of hypertension was significantly higher among participants from KASS (15.2%), compared to KOSS (5.6%), and BOSS (3.7%; P <0.001). Similar but higher prevalence of hypertension among adolescents was found in a study by Kumar et al [18]. On the other hand, another study by Tadesse and Alemu [19] in Ethiopia found a slightly lower prevalence of hypertension (7.7%) among adolescents.…”

“…A cross-sectional study was carried out on adolescent SHS students aged [13][14][15][16][17][18][19]…”

Economic viability of implementing an infrastructure for recycling bedding sand from a free-stall facility for dairy cows

“…Few articles have been found on sand recycling, in the scientific literature (Bradley et al, 2018;Kristula, Rogers, Hogan, & Sabo, 2005;Kumar et al, 2016;Zdanowicz, Shelford, Tucker, Weary, & Keyserlingk, 2004), and none of them evaluate its economic viability. Thus, the present study proposes to examine the economic viability of implementing the necessary infrastructure for the recycling of bedding sand from a free-stall facility in a milk production system in southern Minas Gerais, Brazil.…”