The overall goal of the proposed research is to develop refined methods of quantifying radiation absorbed dose to tumors and other organs using external imaging. The methods will be used to determine the required administration of I131 MIBG for patients undergoing therapy for malignant pheochromocytomas. The approach will be to use daily conjugate-view imaging to establish the curve of relative activity versus time and to employ emission computed tomography (ECT) so as to set the absolute scale of that curve for individual tumors. To assure the accuracy of the ultimate dosimetry, we will 1) obtain consistent volume and activity measurements to prevent build up of error and 2) improve the accuracy of absolute uptake in ECT by obtaining attenuation coefficient maps for each patient. We will achieve these two aims through the use of x-ray transmission computed tomography data. The second will require extrapolation over energy. In addition, we will 3) further improve ECT accuracy by removing or minimizing Compton scatter and by using a high resolution tomograph, SPRINT, for brain tumors instead of the rotating camera tomograph, 4) refine planar conjugate-view imaging so that tumor activity, at least in relative units, is quantified accurately and 5) in cases of complicated tumor shape and of non-uniform tumor uptake, compute an accurate radiation absorbed dose for the individual patient. In these cases, we will compute the dose contribution from beta particles by integration and that from gamma rays by Monte Carlo methods. The development of specifically designed radiopharmaceutical and of monoclonal antibody technology offers the potential of a nearly unlimited array of probes for the diagnosis and treatment of malignant disease. Although the monoclonal field is in its early stages, it offers great promise. If monoclonal antibodies localize into tumors well enough for tumor imaging (and they do in several systems), accurate quantitation of the administered dose to the target organ will be essential for successful and appropriate therapy. Finding a successful protocol in the MIBG case and allowing the documentation of correlation between radiation absorbed dose and degree of tumor response to treatment, based on these calculations, will serve as the ultimate guide for these important therapies of the present and future.
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