DEVELOPMENT OF A 191-OS:191M-IR RADIONUCLIDE GENERATOR

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The development of the 191Os-191m/Ir generator has, until recently, been based on the systematic evaluation of different combinations of ion-exchange material and eluent while retaining the same chemical form of the osmium-191 parent. While incremental improvements have been realized through this approach, these improvements have not, to date, been dramatic enough to facilitate routine clinical use of 191m/Ir for radionuclide angiocardiography. We have recently demonstrated, however, that much greater improvements in generator performance can be achieved through the use of a different chemical form of the osmium-191 parent. Through the use of dicarboxylic acid complexes of osmium(VI) we have developed generators with 2-3 times higher 191m/Ir yield and one-tenth the 191Os breakthrough of earlier designs. In addition, these are the first 191Os-191m/Ir generators that may be used with a physiologically compatible eluent. These generators still, however, have relatively low 191m/Ir yield (30% mL) and the yield decreases with time as a result of photolysis of the osmium complex. The goal of this project is the development of a new 191Os-191m/Ir generator with higher (and constant) 191m/Ir yield that retains the properties of low 191Os breakthrough and a physiologically compatible eluent of the dicarboxylic acid generators. This goal will be achieved through evaluation of a new series of osmium complexes in lower oxidation states (II, III) than those used in any of the previous designs of the 191Os-191m/Ir generator. Osmium complexes in these lower oxidation states will, after beta decay of 191Os, lead directly to stable iridium complexes that may be eluted in high yield. This approach avoids one of the inherent limitations of 191Os-191m/Ir generators using osmium complexes in higher (IV, VI) oxidation states that offer no direct path to an elutable iridium complex and, at the same time, incorporates the results of our earlier studies showing the improvements in generator performance that may be realized through more appropriate choice of the osmium-191 parent complex.