ESTIMATION OF RADIATION ABSORBED DOSES TO THE RED MARROW IN RADIOIMMUNOTHERAPY

Myelotoxicity is the dose-limiting factor in radioimmunotherapy. Traditional methods most commonly used to estimate the radiation adsorbed dose to the bone marrow of patients consider contributions from radionuclide in the blood and/or total body. Targeted therapies, such as radioimmunotherapy, add a third potential source for radiation to the bone marrow because the radiolabeled targeting molecules can accumulate specifically on malignant target cells infiltrating the bone marrow. A noninvasive method for estimating the radiation absorbed dose to the red marrow of patients who have received radiolabeled monoclonal antibodies (MoAb) has been developed and explored. The method depends on determining the cumulated activity in three contributing sources: 1) marrow; 2) blood; and 3) total body. The novel aspect of this method for estimating marrow radiation dose is derivation of the radiation dose for the entire red marrow from radiation dose estimates obtained by detection of cumulated activity in three lumbar vertebrae using a gamma camera. Contributions to the marrow radiation dose from marrow, blood, and total body cumulated activity were determined for patients who received an I-131 labeled MoAb, Lym-1, that reacts with malignant B-lymphocytes of chronic lymphocytic leukemia and nonHodgkin's lymphoma. Six patients were selected for illustrative purposes because their vertebrae were readily visualized on lumbar images. The radiation doses to the marrow contributed by nonpenetrating emissions in the marrow blood and penetrating emissions in the total body were similar in these patients with a mean of 0.2 and 0.3 rads per administered mCi from the blood and total body, respectively. However, the radiation doses to the marrow from nonpenetrating emissions of I-131 that targeted marrow malignancy varied greatly and ranged from 0.6-2.9 rads pwer administered mCi in these selected patients. The latter source of marrow radiation dose was often greater than the combined contribution of the blood and total body to marrow radiation dose; this source of marrow radiation dose is ignored by traditional approaches to bone marrow dosimetry and is important to consider for targeted therapies such as radioimmunotherapy. Although it is not appropriate to suggest that the marrow radiation doses estimated using the novel imaging method described are accurate, their use did predict greater hematologic toxicity in the 6 patients and this toxicity was not anticipated from the marrow radiation doses estimated by using the traditional blood and total body contributions. The exact role of the imaging method remains to be determined and additional validation is required. Although further comparisons with data for hematologic toxicities and results from bone marrow biopsies are required, the method has the potential for providing the therapist with a predictor of greater likelihood of myelotoxicity. Imaging studies with the intended therapeutic agent can be obtained for an individual patient so that predictions can be made before the implementation of therapy.