A single-step kit formulation for the 99mTc-labeling of HYNIC-Duramycin

Introduction: Tc-99m-Duramycin is a unique radiopharmaceutical that binds specifically to phosphatidylethanolamine (PE). The current effort is to develop a single-step kit formulation for the Tc-99m labeling of HYNIC-Duramycin. Methods: A titration series of Tricine/TPPTS coligand systems were tested for an optimal formulation to produce Tc-99m-Duramycin with high radiochemical purity and specific activity. The radiopharmaceutical prepared using the kit formulation was tested for PE binding specificity using polystyrene microbeads coated with different phospholipid species. Radiochemical performance of the kits was assessed after storage at -20 degrees C, room temperature and 37 degrees C. Biodistribution profile of kit-prepared Tc-99m-Duramycin was characterized in healthy rats at 3, 10, 20, 60 and 180 min after intravenous injection. Binding studies were performed using the rat aortic arch and a rat model of myocardial ischemia/reperfusion, which represent scenarios of physiological and pathological PE externalization. Results: A Tricine/IPPTS ratio of 10:1 led to a consistent production of Tc-99m-Duramycin with high radiochemical purity (> 90%), whereas a higher ratio at 40:1 produced radiopharmaceuticals with incomplete substitution of Tricine coligand. Tc-99m-Duramycin prepared using the single-step kit formulation retained PE-binding specificity. The kits are stable over long-term storage. The biodistribution profile of kit-prepared Tc-99m-Duramycin is consistent with HPLC purified radiopharmaceutical from prior studies. Binding studies on a tissue level indicate that the radiopharmaceutical is suitable for studying biological processes that involve PE distribution and redistribution in various physiological and pathological conditions. Conclusion: A single-step kit formulation is developed for Tc-99m-labeling of HYNIC-Duramycin. The radiopharmaceutical has high radiochemical purity and specific activity, retained PE binding activities, amiable to long-term storage, and is injection-ready for in vivo applications. (c) 2012 Elsevier Inc. All rights reserved.