Microdosimetry in Radioimmunotherapy

Antibodies are rapidly being developed which target radionuclides to tumour tissue. The MIRD formulation to calculate absorbed dose from internal emitters has limitations in radiation targeted therapy because of the heterogeneity of antibody distribution through the tumour. This heterogeneity results from vascular and tissue penetration barriers as well as variations in antigen concentration. The problems raised in radioimmunotherapy by the dosimetry of these non-uniform source distributions present an interesting challenge to microdosimetry. Calculations of the mean energy deposition with tumour cell nuclei for randomly distributed 131I and 211At are compared with the case of 131I and 211At-labelled antibody uniformly bound to cell surface antigen. The MIRD dosimetric approach does not address the question of energy deposition at the cellular level, and therefore is unable to differentiate the radiation tumour burden from different source distributions at the microscopic level. Considerable increases in the energy deposition to the cell nucleus may arise due to the geometric weighting of the decay site loci to the periphery of the cell nuclei. The magnitude of this geometric enhancement factor is a function of the inter-cellular distances and the range of the radiation, i.e. the tumour histology and the choice of radionuclide. Methods are being investigated to obtain experimental data for microdosimetric calculations directly from patient tumour biopsy material following the administration of radiolabelled antibody. Automated image analysis techniques are being developed to ascertain the location of the sources and cell nuclear targets using autoradiography and histological staining methods respectively. It is the aim of this study to obtain the distribution of energy deposition to individual cell nuclei from small regions of tumour material in order to obtain a more accurate assessment of tumour cell survival.