We will investigate several new radiopharmaceuticals for measurement of regional intraorgan blood flow which could be particularly valuable for PET imaging. These radiopharmaceutical tracers can be labeled with generator-produced short-lived isotopes, and thus would be more convenient to the researcher than cyclotron-produced isotopes for measuring blood flow, principally H2150 which is produced in individual batches each time it is needed. The proposed radiopharmaceuticals will be useful for quantitating regional blood flow by potentially two different biological mechanisms, and hence two different mathematical models are required for data interpretation. The desmethylimipramine analog is a highly extracted tracer, much like microspheres, and thus the model is simple; flow is proportional to deposition. I-122 is the most likely label for the imipramine derivatives. The cryptates as injected are inert, freely-diffusible tracers much like water and butanol. We envision cryptates labeled with Rb-82, Cs-128, and Ga-68 as possible flow tracers. These complexes may dissociate within cells and leave the tracer metal ion bound to cellular proteins. If so, a more complex, distributed mathematical model for flow will be used. It allows for the transformation of the radiopharmaceutical into one or more additional chemical species. Thus, these experiments also provide a critical forum for comparing the relative merit of two different approaches for measuring blood flow and, when complete, will allow blood flow to be measured more accurately and more conveniently than with H2150.
| Bassingthwaighte, J B; Malone, M A; Moffett, T C et al. (1990) Molecular and particulate depositions for regional myocardial flows in sheep. Circ Res 66:1328-44 |
