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Basic Science Investigations |
-Particle-Emitting Targeted Radiotherapeutics Using Histological Images
1 Department of Radiology, Duke University Medical Center, Durham, North Carolina
2 Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee
The purpose of this study was to evaluate the therapeutic efficacy and limitations of 
-particle-emitting radiolabeled compounds by means of 2-dimensional histological images and distribution of activity on a microscopic level. Methods: A microdosimetric approach based on histological images is used to analyze the therapeutic effectiveness of -particle-emitting 211At and 213Bi conjugated to 201B monoclonal antibody (mAb), which is reactive with murine lung blood vessels for the treatment of EMT-6 lung tumor colonies in nude mice. Autoradiography images were used to define the tissue morphology and activity distribution within lung tissues. Two animal groups were studied: Group A consisted of animals bearing small tumors (<130 µm) and group B consisted of larger tumors (<600 µm). Probability density functions (pdf) described the variability in average absorbed dose and survival probability among normal and tumor target cells and, in turn, were used to assess the survival fraction of tumor and normal tissue. Results: The average absorbed dose to tumor cells per unit cumulated activity concentration for animals in group A was 1.10 x 10-3 and 1.37 x 10-3 Gy g MBq-1 s-1 for 211At and 213Bi, respectively, and for animals in group B was 3.8 x 10-4 and 5.6 x 10-4 Gy g MBq-1 s-1 for 211At and 213Bi, respectively. The fraction of tumor cells that received a zero absorbed dose for animals in group A was 0.04% for 213Bi and 0.2% for 211At and for animals in group B was 25% for 213Bi and 31% for 211At. Both 213Bi- and 211At-labeled 201B mAb were effective therapies for animals with small tumors, where predicted therapeutic effectiveness was consistent with experimental findings; however, they were ineffective for animals with larger tumors. Conclusion: Microdosimetric methods based on knowledge of tissue morphology and activity distribution on a small-scale level can be a useful tool for evaluating a priori the therapeutic efficacy and limitations of targeted -particle endoradiotherapeutic strategies.
Key Words: targeted radiotherapy • radioimmunotherapy • -particle • 213Bi • 211At • autoradiography
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