The overall goal of the proposed research is quantification of radiation absorbed dose delivered to patient tumors by radiopharmaceuticals through the use of external imaging. The preliminary aim is good correlation between calculated absorbed dose and outcome therapy. The ultimate aim is a simple protocol based on tracer measurements so that all and only those who will benefit from a particular treatment receive it. Quantitative results to date document that the conjugate-view method is not consistently accurate for determining tumor activities. Single-Photon-Emission-Computed Tomography (SPECT) activities have been verified by phantom and excised- tissue measurements to be accurage within 15% but further testing and improvement are needed. We propose refining and implementing a new spectral fitting technique for correction of Compton scattering, continuing the investigation of the calculation and use of attenuation maps, and testing new methods to obtain tumor activities, including one based on superimposition of SPECT and Magnetic Resonance (MR) or X-ray Computer Tomography (CT) images. Dosimetric results to date indicate a range of tumor radiation absorbed does from 24.5 Gy (2,450 rads) to 115Gy (11,500) rads) for patients whose pheochromocytomas were treated by 131I metaiodobenzylguanidine (MIBG). Followup of these patients is proceeding. For dosimetry, we plan to check assumptions about homogeneity of uptake by higher resolution imaging, to investigate the effects of irregular tumor shape, to verify that the uptake scales with the activity administered (tracer compared to therapy) and to apply our techniques to MIBG therapy of neuroblastomas in children and to potential monoclonal-antibody therapy of melanoma and ovarian carcinoma. The techniques developed for SPECT quantification in this research should apply to other areas as well, such as thalium heart imaging and single-photon regional-cerebral-blood-flow measurements. Our purpose, in summary, is to seek high accuracy in dosimetric estimates, to reap the benefits of that accuracy in good separation between responders and non-responders and thus to assist in firmly establishing the field of radiopharmaceutical treatment of disease.
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