Bone Marrow Dosimetry Using 124I-PET

Bone marrow is usually dose-limiting for radioimmunotherapy. In this study, we directly estimated red marrow activity concentration and the self-dose component of absorbed radiation dose to red marrow based on PET/CT of 2 different I-124-labeled antibodies (cG250 and huA33) and compared the results with plasma activity concentration and plasma-based dose estimates. Methods: Two groups of patients injected with I-124-labeled monoclonal antibodies (11 patients with renal cancer receiving I-124-cG250 and 5 patients with colorectal cancer receiving I-124-huA33) were imaged by PET or PET/CT on 2 or 3 occasions after infusion. Regions of interest were drawn over several lumbar vertebrae, and red marrow activity concentration was quantified. Plasma activity concentration was also quantified using multiple patient blood samples. The red marrow-to-plasma activity concentration ratio (RMPR) was calculated at the times of imaging. The self-dose component of the absorbed radiation dose to the red marrow was estimated from the images, from the plasma measurements, and using a combination of both sets of measurements. Results: RMPR was observed to increase with time for both groups of patients. Mean (+/- SD) time-dependent RMPR (RMPR(t)) for the cG250 group increased from 0.13 +/- 0.06 immediately after infusion to 0.23 +/- 0.09 at approximately 6 d after infusion. For the huA33 group, mean RMPR(t) was 0.10 +/- 0.04 immediately after infusion, 0.13 +/- 0.05 approximately 2 d after infusion, and 0.20 +/- 0.09 approximately 7 d after infusion. Plasma-based estimates of red marrow self-dose tended to be greater than image-based values by, on average, 11% and 47% for cG250 and huA33, respectively, but by as much as -73% to 62% for individual patients. The hybrid method combining RMPR(t) and plasma activity concentration provided a closer match to the image-based dose estimates (average discrepancies, -2% and 18% for cG250 and huA33, respectively). Conclusion: These results suggest that the assumption of time-independent proportionality between red marrow and plasma activity concentration may be too simplistic. Individualized imaged-based dosimetry is probably required for the optimal therapeutic delivery of radiolabeled antibodies, which does not compromise red marrow and may allow, for some patients, a substantial increase in administered activity and thus tumor dose.