How well does the diagnostic study predict red marrow dose in radioimmunotherapy patients challenged with interferon

Diagnostic doses of radiolabeled antibodies have been used to estimate the radiation absorbed doses for radioimmunotherapy patients enrolled on clinical trials, based on the assumption that the pharmacokinetics are replicated for the subsequent therapy dose. The objective of this study was to compare estimates of red marrow dose from diagnostic and therapy doses of I-131 labeled antibody CC-49 in breast cancer patients challenged with RIFN{alpha}. The whole body retention of the diagnostic and therapy doses was measured from the geometric mean of counts detected with a NaI probe spectrometer system placed at 3 meters from the surface of the abdomen. Whole blood retention of the radiolabeled antibody was estimated from the measured concentration in serial blood samples. The red marrow dose was calculated assuming no specific uptake of the radiolabeled antibody in the skeletal system. In patients who received RIFN{alpha} 5 days prior to the therapy dose, the red marrow dose estimate predicted for the therapy dose from the diagnostic study was underestimated primarily for the blood contribution. In contrast, the red marrow dose in 3 patients who received RIFN{alpha}, administered on the same day as the therapy dose, was unpredictable. These early results indicate that red marrow doses frommore » blood and whole body cannot be predicted from a diagnostic study in patients challenged with these biological response modifiers. In the present trial, therapy activities of I-131 were reduced by about 30%, to reduce the level of hematological toxicity observed in the first patients. These unpredictable in-vivo pharmacokinetics and distribution of I-131 CC-49 make it important to monitor therapy doses in patients and assess if current empirically determined toxicity limits are exceeded.« less