Personalized dosimetry of 131I-rituximab radioimmunotherapy of non-hodgkin lymphoma defined by pharmacokinetics in bone marrow and blood.

PURPOSE: To report a comparison of SPECT/CT technique with standard blood-based dosimetry methodology in a cohort of non-Hodgkin lymphoma (NHL) patients treated with 131I-rituximab anti-CD20 chimeric monoclonal antibody.

METHODOLOGY: Red marrow uptake was measured directly using serial quantitative whole-body imaging in conjunction with SPECT/CT in a cohort of 23 patients undergoing routine 131I-rituximab radioimmunotherapy of NHL. Absorbed dose measurements were then compared with radiation doses calculated using standard peripheral blood counting methodology.

RESULTS

Activity clearance from whole body of 88.7 hours measured by imaging 131I-rituximab was significantly slower (p<0.001) than the mean effective half-life clearance of 60.8 hours calculated from the sampling peripheral blood. The mean activity concentrations in bone marrow measured using SPECT/CT, and by blood sampling, extrapolated to the time of administration, were, however, concordant. The absorbed self-dose in red marrow, measured using imaging, was 1.02 Gy compared with the dose (0.81 Gy) calculated from blood sampling. Neutrophil toxicity correlated with absorbed dose by SPECT/CT imaging (p=0.01), whereas the blood sampling method demonstrated no correlation with any parameters of hematological toxicity.

CONCLUSION

Radiation dose to red marrow from 131I-rituximab is inherently underestimated by standard indirect peripheral blood counting methods. Personalized marrow dosimetry by quantitative gamma imaging more accurately predicts of hemopoietic myelotoxicity by direct measurement of the bone marrow activity concentration of 131I-rituximab.