Tc-99m-ethylenedicysteine-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 of folate and folate analogs such as methotrexate and overexp ressed on various tumor cells. However these receptors are highly restricte d in normal differentiated tissues. Results of limited in vitro and in vivo animal studies suggest that folate receptors could be a potential target f or tumor imaging. This study aimed to develop a Tc-99m-labeled folic acid u sing ethylenedicysteine (EC) as a chelator and evaluate its labeling effici ency and potential use as a tumor seeking agent. Tissue distribution of Tc- 99m-EC-folate was determined in breast tumor-bearing mts at 20 min, 1, 2 an d 4 h (n=3/time interval. 370 KBq/rat, i.v.). Blocking study was employed t o determine receptor-mediated process; Tc-99m-EC-folate was co-administrate d with 50 and 150 mu mol/kg of cold folic acid to tumor bearing rats. Plana r imaging and whole-body autoradiograms were performed The data was compare d to that using Tc-99m-EC (control). In animal studies, tumor/blood count d ensity ratios at 20 min-4 h increased from 0.81+/-0.09 to 1.23+/-0.13 with Tc-99m-EC-folate. Conversely, these values showed time-dependent decrease f rom 0.77+/-0.32 to 0.65+/-0.01 with Tc-99m-EC in the same time period. Tumo r/muscle and tumor/blood count density ratios significantly decreased with folic acid co-administrations. Planar images and autoradiograms confirmed t hat the tumors could be visualized clearly with Tc-99m-EC-folate.