99m Tc-Ethylenedicysteine-Folate: A New Tumor Imaging Agent. Synthesis,Labeling and Evaluation in Animals

Abstract

It is known that membrane folie acid receptors are responsible for cellular accumulation offolate and folate analogs such as methotrexate and overexpressedon various tumor cells. However, these receptors are highly restricted in normal differentiated tissues. Results of limited in vitro and in vivo animal studies suggest that folate receptors could be a potential target for tumor imaging. This study aimed to develop a ^99mTc-labeled folic acid using ethylenedicysteine (EC) as a chelator and evaluate its labeling efficiency and potential use as a tumor seeking agent. Tissue distribution of^99mTc-EC-folate was determined in breast tumor-bearing rats at20min, 1, 2, and4h (n=3/time interval, 370KBq/rat, i.V.). Blocking study was employed to determine receptor-mediated process; ^99mTc-EC-folate was co-administrated with 50 and 150 pmol/kg of cold folie acid to tumorbearing rats. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using ^99mTc-EC (control). In animal studies, tumor/blood count density ratios at 20 min-4 h increased from 0.81±.0.09 to 1.23±0.13 with ^99mTc-EC-folate. Conversely, these values showed time-dependent decrease from 0.77±0.32 to 0.65±0.01 with ^99mTc-EC in the same time period. Tumor/muscle and tumor/blood count density ratios significantly decreased with folic acid co-administrations. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with ^99mTc-EC-folate.