Molecular Imaging of Mesothelioma withT99mc-ECG andG68a-ECG

Abstract

We have developed ethylenedicysteine-glucosamine (ECG) as an alternative to18F-fluoro-2-deoxy-D-glucose (18F-FDG) for cancer imaging. ECG localizes in the nuclear components of cells via the hexosamine biosynthetic pathway. This study was to evaluate the feasibility of imaging mesothelioma withT99mc-ECG andG68a-ECG. ECG was synthesized from thiazolidine-4-carboxylic acid and 1,3,4,6-tetra-O-acetyl-2-amino-D-glucopyranose, followed by reduction in sodium and liquid ammonia to yield ECG (52%). ECG was chelated withT99mc/tin (II) andG68a/69Ga chloride forin vitroandin vivostudies in mesothelioma. The highest tumor uptake ofT99mc-ECG is 0.47 at 30 min post injection, and declined to 0.08 at 240 min post injection. Tumor uptake (%ID/g), tumor/lung, tumor/blood, and tumor/muscle count density ratios forT99mc-ECG (30–240 min) were0.47±0.06to0.08±0.01;0.71±0.07to0.85±0.04;0.47±0.03to0.51±0.01, and3.49±0.24to5.06±0.25; forG68a-ECG (15–60 min) were0.70±0.06to0.92±0.08;0.64±0.05to1.15±0.08;0.42±0.03to0.67±0.07, and3.84±0.52to7.00±1.42; for18F-FDG (30–180 min) were1.86±0.22to1.38±0.35;3.18±0.44to2.92±0.34,4.19±0.44to19.41±2.05and5.75±2.55to3.33±0.65, respectively. Tumor could be clearly visualized withT99mc-ECG andG68a-ECG in mesothelioma-bearing rats.T99mc-ECG andG68a-ECG showed increased uptake in mesothelioma, suggesting they may be useful in diagnosing mesothelioma and also monitoring therapeutic response.