Microdosimetric concepts in radioimmunotherapy.

In microdosimetry particular emphasis is placed on the stochastic fluctuation of dose in small target volumes such as individual cell nuclei or chromatin fiber, and their relevance to radiobiologic toxicity. Thus microdosimetry is intimately associated with models of radiation action. There are three principal areas where microdosimetry has been applied: (1) radiation protection, (2) high LET radiotherapy, e.g., neutron therapy, and (3) incorporated radionuclides, and in this latter category the importance of microdosimetry to the radiobiology of radiolabeled antibodies is becoming increasingly recognized. The objective of microdosimetry is the complete characterization of energy deposition within all target volumes throughout the tissue of interest. The importance and relevance of this pursuit will depend upon the properties of the radionuclide emissions and the spatial distribution of the radionuclide relative to the target volumes. If the distribution of internal emitters within both malignant and normal tissue is uniform, the application of microdosimetry to radioimmunotherapy (RIT) is limited to alpha-emitters and Auger emitters. Under such circumstances the traditional MIRD formalism for the evaluation of tumor and tissue doses from the commonly used beta-emitters is entirely adequate. This, however, is rarely the case. When the distribution of radiolabeled antibody is nonuniform, techniques of dose averaging over volumes greater in size than the individual target volumes can become inadequate predictors of the biological effect. The concepts, methods, and realm of applicability of microdosimetry within the field of radioimmunotherapy are emphasized in this paper.