Core A core Director: Bading, James Principal investigator: Raubitschek, Andrew DESCRIPTION: The overall objective of Core A is to provide state-of-the-art imaging, radiation dosimetry and pharmacokinetic modeling support for clinical trials of novel radiolabeled monoclonal antibodies (MAbs) and other immunotherapeutic agents. The primary responsibility of the Core is to help the principal investigators of our research projects optimize the use of imaging in their clinical study protocols. To that end, the Core will (a) identify and implement current best practices for quantitative imaging, dosimetry of internally administered radioisotopes, and the use of imaging to assess and predict tumor response to therapy;and (b) perform research/development as needed to optimize the use of imaging in the clinical study protocols. The Core A team will also provide quality assurance for instrument calibration and clinical scan acquisition. Core A is led by two highly experienced imaging physicist/radiation dosimetrist/kinetic modelers and also ncludes a radiologist expert in clinical applications of functional imaging, an image analyst/programmer, a data base administrator/developer and an imaging research technician. A full complement of modern clinical maging equipment is available, including SPECT-CT and PET-CT (by the initiation of the grant). Another key equipment resource is a well-integrated image processing, display and analysis system dedicated to linical research studies. In the area of pharmacokinetics and radiation dosimetry, the Core will (a) continue to perform quantitative image analysis and dosimetric calculations for clinical radioimmunotherapy (BIT) trials;(b) supplement planar imaging with SPECT-CT to improve accuracy of radioactivity measurements in tumors and normal organs;(c) implement a 3D, voxel-based method for estimating radiation absorbed dose;(d) evaluate the impact of SPECT-CT and voxel-based dosimetry on the correlation between estimated tumor absorbed dose and response;(e) evaluate the use of kinetic modeling to differentiate among the factors affecting tumor uptake of BIT MAbs;and (f) evaluate the effect of the anti-angiogenesis agent Avastin on tumor uptake of RIT MAbs. The Core will also undertake a major effort in the area of assessment of treatment response by (a) establishing an image response assessment team (IRAT);(b) implementing a quality assurance program for measurements of tumor response to treatment;and (c) evaluating the use of a functional/metabolic measure of tumor response (PET/[18F]FDG) in our clinical therapy trials. Core A directly supports Project 1 and Project 3, which together contain all of the clinical trials proposed for the next five years. Core A provides imaging physics, pharmacokinetic modeling and radiation dosimetry support to Core D (Animal Core);Core A also has primary responsibility for translating imaging advances developed in animals into clinical use. Core A indirectly supports Project 2 by developing modeling methodology that will contribute to clinical trial design for pretargeted RIT. Core A receives support from Core E (Biostatistics) in the areas of experimental design and data management.