Abstract
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Objectives We have developed a chelator-based ethylenedicysteine-glucosamine (ECG) as an alternative to F-18-fluoro-2-deoxy-D-glucose (FDG) for cancer imaging. EC-G localizes in the nuclear components of cells primarily via the hexosamine pathway whereas FDG localizes in the cytoplasm of cells through the glycolytic pathway. Clinic studies revealed that Tc-99m-ECG could increase the specificity in oncology applications. Ga-68 (89% positron, 68 min half-life) has significant commercial potential because it can be produced from a generator on-site which is pivotal to clinical applications. This study was aimed to evaluate the feasibility of imaging mesothelioma with Ga-68 ECG.
Methods EC-G was synthesized by reacting thiazolidine-4-carboxylic acid with 1,3,4,6-tetra-O-acetyl-2-aminoglucopyranose and 1-hydroxybenzotriazole, followed by reduction with sodium in liquid ammonia to yield EC-G (52%). ECG was chelated with Ga-66/Ga-68 chloride at 55oC for 10 min. A mesothelioma cell line (IL-45) was selected to create the animal model. Biodistribution (n=3/time interval) and micro-PET imaging of Ga-68 ECG and F-18 FDG were conducted in mesothelioma-bearing male F-344 rats from 15-180 min.
Results Radiochemical purity of Ga-68 ECG was >95% (by TLC and HPLC). In the rat biodistribution, tumor uptake (%ID/g), tumor/lung, tumor/blood and tumor/muscle count density ratios with Ga-68 ECG (15-60 min) were 0.70±0.06 to 0.92±0.08; 0.64±0.05 to 1.15±0.08; 0.42±0.03 to 0.67±0.07, and 8.81±1.54 to 13.20±2.78; with F-18 FDG (30-180 min) were 1.38±0.35 to 1.86±0.22; 2.92±0.34 to 3.18±0.44, 4.19±0.44 to 19.41±2.05 and 0.94±0.16 to 2.50±0.37, respectively. Tumor could be visualized clearly with Ga-68 ECG and F-18 FDG at 45 min in mesothelioma-bearing rats by PET.
Conclusions An increased uptake of Ga-68 ECG in the mesothelioma model demonstrates the feasibility of Ga-68 ECG in monitoring therapeutic response and for theranostic approaches in cancers