Patient-Specific Dosimetry and Radiobiological Modeling of Targeted Radionuclide Therapy Grant - final report

George Sgouros, Ph.D.

George Sgouros, Ph.D./Johns Hopkins University, School of Medicine

关键词: Targeted Radionuclide Therapy;    Atomic Number;    Dosimetry;    Hypothesis;    Radiobiology;   

DOI  :  10.2172/901074
RP-ID  :  DOE/ER/23967-final
RP-ID  :  FG02-05ER63967
RP-ID  :  901074

美国|英语

来源: UNT Digital Library

【 摘 要 】

The broad, long-term objectives of this application are to 1. develop easily implementable tools for radionuclide dosimetry that can be used to predict normal organ toxicity and tumor response in targeted radionuclide therapy; and 2. to apply these tools to the analysis of clinical trial data in order to demonstrate dose-response relationships for radionuclide therapy treatment planning. The work is founded on the hypothesis that robust dose-response relationships have not been observed in targeted radionuclide therapy studies because currently available internal dosimetry methodologies are inadequate, failing to adequately account for individual variations in patient anatomy, radionuclide activity distribution/kinetics, absorbed dose-distribution, and absorbed dose-rate. To reduce development time the previously available software package, 3D-ID, one of the first dosimetry software packages to incorporate 3-D radionuclide distribution with individual patient anatomy; and the first to be applied for the comprehensive analysis of patient data, will be used as a platform to build the functionality listed above. The following specific aims are proposed to satisfy the long-term objectives stated above: 1. develop a comprehensive and validated methodology for converting one or more SPECT images of the radionuclide distribution to a 3-D representation of the cumulated activity distribution; 2. account for differences in tissue density and atomic number by incorporating an easily implementable Monte Carlo methodology for the 3-D dosimetry calculations; 3. incorporate the biologically equivalent dose (BED) and equivalent uniform dose (EUD) models to convert the spatial distribution of absorbed dose and dose-rate into equivalent single values that account for differences in dose uniformity and rate and that may be correlated with tumor response and normal organ toxicity; 4. test the hypothesis stated above by applying the resulting package to patient trials of targeted radionuclide therapy to obtain normal organ and tumor dose vs. response correlations. Completion of the aims outlined above will make it possible to perform patient-specific dosimetry that incorporates considerations likely to provide robust dose-response relationships. Such an advance will improve targeted radionuclide therapy by making it possible to adopt treatment planning methodologies.