Radioimmunotherapy with 90Y-DOTA-BC8 (anti-CD45 Antibody): Effect of Spleen Size and Uptake on Bone Marrow Absorbed Dose

Abstract

1018 Objectives 90Y-DOTA-BC8 (anti-CD45 antibody) is being investigated as a treatment for hematologic malignancies in several ongoing clinical trials at the Fred Hutchinson Cancer Research Center. We analyzed the effect of spleen size and relative splenic uptake (%ID/g) of radiolabeled antibody on the absorbed dose to bone marrow. Methods: We reviewed biokinetic data on 39 patients who received radiotracer infusions of (129.5 to 406 MBq) 111In-DOTA-BC8 (0.5 or 0.75 mg/kg) followed by serial gamma camera imaging. Iliac crest bone marrow biopsies were obtained approximately 24 hours after antibody infusion to calculate the percent of administered activity (% ID/g) in marrow and to normalize the marrow time-activity curves from direct counting for dosimetry. Patient-specific organ absorbed doses were calculated with correction for organ volumes obtained from CT scans. We compared the calculated red marrow dose with spleen size and splenic uptake to ascertain whether the spleen acts as a sink for radiolabeled antibody and reduces the dose to the marrow. Results: Spleen size ranged from 62 to 758 cm3 (321.692 ± 144.33); initial antibody uptake in the spleen ranged from 0.054 to 0.317 % ID/g (0.184 ± 0.069). Calculated marrow doses ranged from 1.98 to 26.8 cGy/mCi (12.39 ± 7.70). Increasing spleen size reduced the marrow dose, but measurement uncertainties associated with biopsy specimen marrow content may have reduced the correlation coefficient (r = 0.25). The spleen acts as a natural sink for radiolabeled antibody which reduces uptake and retention of radiolabeled antibody in red marrow. Conclusions: Radioimmunotherapy with 90Y-DOTA-BC8-antibody has the ability to deliver substantial radiation doses to hematopoietic tissues in patients treated for hematologic malignancies. Spleen size weakly correlated with both red marrow clearance half-time (r = 0.19) and marrow dose (r = 0.25). (Research was supported by NCI P01CA044991, K08CA151682, and the David and Patricia Giuliani Family Foundation.

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