188Re-ethylene dicysteine:: a novel agent for possible use in endovascular radiation therapy

Several agents, such as (ReO4)-Re-188 -, Re-188-MAG(3) and Re-188-DTPA are currently under investigation as radiation sources in Liquid-filled balloons for prevention of restenosis following coronary angioplasty. Bearing in mind the risk factor associated with leakage of radioactivity in the event of balloon rupture, the criteria sought in selecting suitable agents for endovascular radiation therapy (EVRT) are rapid clearance and low dose to vital organs. Since Tc-99(m) labelled ethylene dicysteine (EC) is a well established agent for renal tubular function imaging, the use of Re-186-ethylene dicysteine as a potential agent for prevention of restenosis after angioplasty has been evaluated previously. Therefore, it was of interest to evaluate the applicability of the more potential isotope of rhenium, Re-188, a high energy beta -emitter (E-beta max = 2.12 MeV) with a suitable T-1/2 = 16.9 h, Obtainable carrier-free from the W-188-Re-188 generator, as an attractive and alternative radionuclide for labelling with L,L-EC. in this paper, the preparation and pharmacological behaviour of the Re-188 complex of ethylene dicysteine are reported. The complex can be prepared in high yields (99.5%) under optimized conditions of pH 2-3, at a ligand concentration of 15 mM, 50 mug (0.18 mM) carrier rhenium and using 2 mg.mL(-1) stannous chloride. On storage at 4 degreesC, the RC purity was more than 97% after 48 h when prepared under optimum conditions. Biodistribution studies in Wistar rats showed the desired characteristics of fast blood clearance and low retention of activity in the vital organs (<2% in intestine, <1% in stomach, <0.5% in Liver) with a high renal excretion (90.65 +/- 0.6%) at 3 h post-injection. These results confirm the advantages of using the Re-188-EC complex compared with perrhenate and other rhenium radiopharmaceuticals currently being used in balloons for EVRT. ((C) 2000 Lippincott Williams & Wilkins).