RADIATION-DOSIMETRY FOR RADIOIMMUNOTHERAPY - AN OVERVIEW OF CURRENT CAPABILITIES AND LIMITATIONS

Background. The two major uncertainties associated with absorbed dose calculations involve: (1) measurement errors from assessment of radioa ctivity in specific organs and tissues by direct counting; and (2) app lication of standard anthropomorphic and biokinetic models for dose as sessment. Uncertainties in direct counting result from the inherent di fficulty of measuring radioactivity inside the body, Although the syst em recommended by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine provides a general framework and c onceptual basis for the dosimetry of administered radiopharmaceuticals , it does not provide complete methods for assessing some of the more important quantities of interest in radioimmunotherapy, such as dose t o tumors and descriptions of spatial dose distributions within tissues . Current MIRD anthropomorphic models are only crude representations o f the human body. Generalized biokinetic models used in the MIRD syste m may vary considerably from the actual biokinetics of radiolabeled co mpounds in the body. This review describes limitations of the present MIRD system for radioimmunotherapy; they include assumptions used in t reatment planning and the lack of specific methods for tumor dosimetry , multi-cellular dosimetry, microdosimetry, small animal dosimetry, an d uncertainty analysis. Conclusions. Treatment planning for radioimmun otherapy requires patient-specific organ models and customized biokine tic parameters. Improvements are also needed in marrow dosimetry to ac count for the amount and distribution of red marrow relative to that f ound in adjacent source regions, skeletal structures, and circulating blood. Simplified assumptions with regard to the locally absorbed frac tion of beta-particle energy in tissues adjacent to source regions sho uld not be used when depth-dose profiles are needed; for example, radi ation absorbed doses to intestinal walls should be calculated over the entire mass of tissue or described by absorbed-dose distributions. Ad ditional research is needed to develop improved measurement techniques and computational methods to assess more accurately internal dose dis tributions within tumors and normal tissues.