^99mTc-EthyIenedicysteine-Folate: A new tumor imaging agent. synthesis, labeling and evaluation in animals

It is known that membrane folic acid receptors are responsible for cellular accumulation offolate andfolate analogs such as methotrexate and overexpre'ssed on 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. TJiis 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 at 20 min, l, 2, and 4 h (n =3/time interval, 3 70 KBq/rat, i. v.J. Blocking study was employed to determine receptormediated process; ^99mTc-EC-folate was co-administrated with 50 and 150 umol/kg of cold folic acid to tumorbearing rats. Planar imaging and whole-body autoradiograms were performed. Tlie data was compared to that using Tc-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.