Internal dosimetry. Macroscopic, small-scale and microscopic perspectives

Internal dosimetry deals with the assessment of absorbed dose for radionuclides distributed inside the body. The absorbed dose is in its turn used for correlation with the biological effect caused by the irradiation. In radioimmunotherapy is however the correlation not easily found and factors influencing this are evaluated and discussed in this work. The internal dosimetry could be subdivided into three levels; macroscopic, small-scale, and microscopic dosimetry. Macroscopic dosimetry: The MIRD S formalism is used to assess the mean absorbed dose to normal organs and tissues. The activity distribution is assumed to be uniform and the calculated mean absorbed dose serves as a good representation of the absorbed dose since the volumes are large compared to the range of emitted particles. The mean absorbed dose to normal organs and tumours was determined for B-cell lymphoma patients undergoing radioimmunotherapy with 90Y-hLL2 (Paper I). The absorbed dose to bone marrow, which is the most radiation sensitive tissue in the body, could be calculated via a method based on the activity in blood samples. The ratio of the activity concentration in bone marrow to the activity concentration in blood was, however, found not to be constant over time. A method for taking this into account in the calculations was proposed (Paper II). Lymphomas are in general radiation sensitive, fast-responding tumours. A decrease in the mass of a tumour during the course of radioimmunotherapy could have a strong influence on the calculated absorbed dose and a method for correction due to this effect was developed (Paper III). Small-scale dosimetry: The MIRD formalism is used, but as the volume is smaller, the mean absorbed dose serves as a poorer representation of the absorbed dose. A model of the anatomy of a mouse was developed and the influence on the S values (absorbed dose per decay) for the choice of organ mass, shape of the organs and distances between the organs was investigated (Paper IV). The average number of atoms per tumour cell was determined from blood samples from a patient having a B cell lymphoma. The MIRD cellular S values were used for calculation of the mean absorbed dose to a cell (Paper V). Internal microdosimetry: The absorbed dose is the expectation value of the specific energy, which is a quantity that takes stochastic effects of the energy depositions into account. The smaller a volume, the larger stochastic effects are seen. Lymphoma patients could have a leukaemic spread of their disease and as 90Y often is used for therapy, the treatment to the single tumour cells is not optimized. Theoretical calculations were performed based on experimental data for an evaluation (Paper VI).