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Therapeutic Potential of ⁹⁰Y- and ¹³¹I-Labeled Anti-CD20 Monoclonal Antibody in Treating Non-Hodgkin's Lymphoma with Pulmonary Involvement: A Monte Carlo–Based Dosimetric Analysis

¹ Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, Maryland; and ² Division of Medical Imaging Physics, Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, Maryland

Correspondence: For correspondence or reprints contact: George Sgouros, PhD, CRB II 4M.61, 1550 Orleans St., Johns Hopkins University, School of Medicine, Baltimore, MD 21231. E-mail: gsgouros{at}jhmi.edu

Pulmonary involvement is common in patients with non-Hodgkin's lymphoma (NHL). ⁹⁰Y- and ¹³¹I-anti-CD20 antibodies (ibritumomab tiuxetan and tositumomab, respectively) have been approved for the treatment of refractory low-grade follicular NHL. In this work, we used Monte Carlo–based dosimetry to compare the potential of ⁹⁰Y and ¹³¹I, based purely on their emission properties, in targeted therapy for NHL lung metastases of various nodule sizes and tumor burdens. Methods: Lung metastases were simulated as spheres, with radii ranging from 0.2 to 5.0 cm, which were randomly distributed in a voxelized adult male lung phantom. Total tumor burden was varied from 0.2 to 1,641 g. Tumor uptake and retention kinetics of the 2 radionuclides were assumed equivalent; a uniform distribution of activity within tumors was assumed. Absorbed dose to tumors and lung parenchyma per unit activity in lung tumors was calculated by a Monte Carlo–based system using the MCNP4B package. Therapeutic efficacy was defined as the ratio of mean absorbed dose in the tumor to that in normal lung. Dosimetric analysis was also performed for a lung-surface distribution of tumor nodules mimicking pleural metastatic disease. Results: The therapeutic efficacy of both ⁹⁰Y and ¹³¹I declined with increasing tumor burden. In treating tumors with radii less than 2.0 cm, ¹³¹I targeting was more efficacious than ⁹⁰Y targeting. ⁹⁰Y yielded a broader distribution of tumor absorbed doses, with the minimum 54.1% lower than the average dose; for ¹³¹I, the minimum absorbed dose was 33.3% lower than the average. The absorbed dose to normal lungs was reduced when the tumors were distributed on the lung surface. For surface tumors, the reductions in normal-lung absorbed dose were greater for ⁹⁰Y than for ¹³¹I, but ¹³¹I continued to provide a greater therapeutic ratio across different tumor burdens and sizes. Conclusion: Monte Carlo–based dosimetry was performed to compare the therapeutic potential of ⁹⁰Y and ¹³¹I targeting of lung metastases in NHL patients. ¹³¹I provided a therapeutic advantage over ⁹⁰Y, especially in tumors with radii less than 2.0 cm and at lower tumor burdens. For both ⁹⁰Y- and ¹³¹I-labeled antibodies, treatment is more efficacious when applied to metastatic NHL cases with lower tumor burdens. ¹³¹I has advantages over ⁹⁰Y in treating smaller lung metastases.

Key Words: non-Hodgkin's lymphoma • pulmonary metastases • dosimetry • Monte Carlo • ⁹⁰Y • ¹³¹I

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