In Vitro Stability Evaluation of Rhenium-188-MAG3: A Potential Therapeutic Agent for Prevention of Restenosis after Percutaneous Transluminal Coronary Angioplasty

Backgrounds: Following coronary angioplasty restenosis occurs in ≥30% of cases. Local irradiation of the stenosed artery immediately after angioplasty using 188Re-MAG3 delivered into the diseased vessel via a balloon to prevent the restenosis is currently under investigation (IND). A potential complication of the procedure is balloon rupture. The aim of this study is to evaluate the radiochemical stability of 188Re-MAG3. Stable 188Re- MAG3, in unlikely event of balloon rupture, will be quickly eliminated via the kidneys, with a resultant acceptability low whole body radiation dose. Unstable 188Re- MAG3, which is retained in various organs results in a greater radiation burden to the patient. Methods: 188Re-MAG3 (3.7 GBq/ml) was prepared, and the product was evenly divided into 5 sample groups: control (without ascorbic or gentisic acid), with 25 mg of ascorbic acid, with 50 mg of ascorbic acid, with 1 mg of gentisic acid, and with 2 mg of gentisic acid. The samples were kept at room temperature. The in vitro stability of each sample was analyzed (N=3) by using ITLCSG/ normal saline, TLC-SG 60/acetonitrile, and Sep- Pak C18 column /0.001N HCl, ethanol/normal saline systems at 0, 3, 6 and 24 h after preparation. Results: The results demonstrated that the mean radiochemical purity of the control sample decreased from 97% to 80% at 3 h, to 59% at 6 h, and to 4% at 24 h after preparation. In the presence of either 25 mg or 50 mg of ascorbic acid, the stability of 188Re-MAG3 was fully preserved after 24 h. In the presence of 1 mg or 2 mg of gentisic acid, the stability of 188Re-MAG3 was fully preserved up to 6 h after preparation. Conclusion: The presence of ascorbic acid (25~50 mg) is needed to maintain in vitro stability of 188Re-MAG3.