Ultra-short lived radionuclides obtained from generator systems have important potential in nuclear medicine for first-pass studies of the heart and other organs. A second major application for such radionuclides which remain in the vascular space is the ability to monitor regional organ perfusion under continuous infusion conditions (steady state). The advantages of such short- lived radionuclides are the ability to make high quality, repeated measurements over a short interval of time with a low-absorbed radiation dose to patients and personnel. It is also possible to benefit from the ultra-short half-life of such a tracer to accurately measure mean transit times and to thus, consequently, also have the opportunity to assess local perfusion rates. For such versatile and cost-effective use such a generator must have a parent radionuclide with a sufficiently long half-life which would allow a useful """"""""shelf-life"""""""" of several days or longer. Breakthrough should be as low as possible and a short-lived daughter emitting photons between 100-200 keV would allow the use of widely available Anger-type camera systems. There are few possible generator pairs which meet these requirements. We have developed a """"""""prototype"""""""" osmium-191 (15 days)/iridium- 191m (4.9 sec) generator system using activated carbon as the absorbent which fulfills the above requirements. We propose to further develop and optimize this generator system by a detailed evaluation of the chemistry involved in elution of Ir-191m in high yield and to pursue a comprehensive evaluation of a number of carbon products and other exchangers to optimize generator performance in both the """"""""bolus"""""""" and """"""""continuous infusion"""""""" modes. We also propose to develop an automated elution system which will allow reproducible use. In parallel with generator development, we plan to supply the generator to develop methods for the evaluation of regional myocardial, cerebral and renal perfusion under continuous infusion conditions in laboratory animals. As prototype systems are made available they will also be supplied to collaborators for further preclinical testing to evaluate the use of Ir-191m for a variety of applications and for potential clinical evaluation.
