MICRODOSIMETRIC CONCEPTS IN RADIOIMMUNOTHERAPY

In microdosimetry particular emphasis is placed on the stochastic fluc tuation of dose in small target volumes such as individual cell nuclei or chromatin fiber, and their relevance to radiobiologic toxicity. Th us microdosimetry is intimately associated with models of radiation ac tion. There are three principal areas where microdosimetry has been ap plied: (1) radiation protection, (2) high LET radiotherapy, e.g., neut ron therapy, and (3) incorporated radionuclides, and in this latter ca tegory the importance of microdosimetry to the radiobiology of radiola beled antibodies is becoming increasingly recognized. The objective of microsdosimetry is the complete characterization of energy deposition within all target volumes throughout the tissue of interest. The impo rtance and relevance of this pursuit will depend upon the properties o f the radionuclide emissions and the spatial distribution of the radio nuclide relative to the target volumes. If the distribution of interna l emitters within both malignant and normal tissue is uniform, the app lication of microdosimetry to radioimmunotherapy (RIT) is limited to a lpha-emitters and Auger emitters. Under such circumstances the traditi onal MIRD formalism for the evaluation of tumor and tissue doses from the commonly used beta-emitters is entirely adequate. This, however, i s rarely the case. When the distribution of radiolabeled antibody is n onuniform, techniques of dose averaging over volumes greater in size t han the individual target volumes can become inadequate predictors of the biological effect. The concepts, methods, and realm of applicabili ty of microdosimetry within the field of radioimmunotherapy are emphas ized in this paper.