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

Abstract

It is known that membrane folic acid receptors are responsible for cellular accumulation of folate and folate analogs such as methotrexate and overexpressed 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. 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 at 20 min, 1, 2, and 4 h (n = 3/time interval, 370 KBq/rat, i.v.). Blocking study was employed to determine receptor-mediated process; 99mTc-EC-folate was co-administrated with 50 and 150 mumol/kg of cold folic acid to tumor-bearing 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.

Imaging and dosimetry of 99mTc EC annexin V: Preliminary clinical study targeting apoptosis in breast tumors

“…99m Tc-ethylenedicysteine ( 99m Tc-EC) is a successful example of N 2 S 2 chelates. Using a standard coupling technique, 99m Tc-EC-drug conjugates were then developed to characterize tumor tissues (15,16). In the previous report, we have described in vivo biodistribution and planar imaging studies in tumor-bearing rats given 99m Tc-EC annexin V ( 99m Tc-EC-ANX), and have demonstrated the pharmacokinetic distribution of the tracer and feasibility of using 99m Tc-EC-ANX to image apoptosis-induced tumor (17).…”

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“…Consequently, an assortment of folate conjugated imaging agents, including radiopharmaceuticals, [135][136][137][138][139][140][141][142][143] fluorescent dyes, MRI contrast agents, and PET imaging agents, 134 have been synthesized and tested in vivo. In general, both contrast and sensitivity are good, suggesting that many imaging applications of folate targeting may eventually be developed.…”

Tumor Specific Imaging Using Tc-99m and Ga-68 Labeled Radiopharmaceuticals

“…Tc efficiently with high radiochemical purity and the preparation remains stable for several hours [12][13][14][15][16][17][18][19][20][21][22].…”