Chemical Synthesis, Kit Preparation And Comparative Study Of ～(99m)Tc-EIBI And ～(99m)Tc-Tetrofosmin

PURPOSE.Chemical synthesis and kit preparation of two novel myocardial perfusion imaging agents, ^99mTc-EIBI and ^99mTc-Tetrofosmin, have been described here. Clinical phase I trials of ^99mTc-Tetrofosmin, prepared in our own laboratory, were carried out. The physicochemical and bioligical properties of both ^99mTc-EEBI and ^99mTc-Tetrofosmin were compared with those of ^99mTc-MIBI.METHODS:1. EIBI: The carrier EIBL, isolated as CuBF₄(EIBI)₄, was synthesized in four steps. Lyophilized formulation was developed by means of Latin-square design to fix the proportion of kit components and optimal pH value, using the Cardiolite^? prescription (DuPont Pharma) as reference. The labelling yield or radiochemical purity of ^99mTc-EIBI under different labelling conditions of pertechnetate volume, labelling time arid specific activity of pertechnetate was determined by using both HPLC and Polyamide-TLC. The radiochemical purity was measured at intervals after EIBI-kit reconstitution at room temperature, and the stablility of different kit samples of EIBI-kit stored in refrigerator was also checked in order to ascertain the shelf life. Sterility, apyrogens and undue toxicity were tested according to the methods described in The Chinese Pharmacopoeia (1990). Biodistribution of ^99mTc-EIBI in mice was estimated as the percentage of injected dose (%ID), the percentage of injected dose per gram (%ID/g), and the ratio of target to non-target (T/NT) in various organs and tissues.2. Tetrofosmin: The ligand tetrofosmin was synthesized in four steps and a freeze-dried tetrofosmin kit was prepared, following the Myoview^TM prescription (Amersham International plc.) with some modifications. The labeling yield and radiochemical purity were determined by ITLC-SG, PC and HPLC. The radiochemical purity was measured at...