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Department of Internal Medicine, University of California Davis Medical Center, Sacramento
Department of Chemistry, University of California Davis, Davis, California
Correspondence: For correspondence or reprints contact: Gerald L. DeNardo, MD, Molecular Cancer Institute, Section of Radiodiagnosis and Therapy, 1508 Alhambra Blvd., Ste. 3100, Sacramento, CA 95816.
ABSTRACT
Several monoclonal antibodies, including Lym-1, have proven effective for treatment of hematotogic malignancies. Lym-1, which preferentially targets malignant lymphocytes, has induced therapeutic responses and prolonged survival in patients with non-Hodgkin's lymphoma (NHL) when labeled with 131I. Because radkxnetal-labeled monoclonal antibodies provide higher tumor radiation doses than corresponding 131I-labeled monoclonal antibodies, the radiation dosimetry of 90Y-2-iminothiolane-2-[p-(bromoacetamido)benzyl]-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-teraacetic acid-Lym-1 (90Y-21T-BAD-Lym-1) is of importance because of its potential for radommunotherapy. Although 90Y has attractive properties for therapy, its secondary bremsstrahlung is less suitable for imaging and pharmacokinetic studies in patients. Thus, the pharmacokinetic data obtained for 111In-2IT-BAD-Lym-1 in patients with NHL were used to calculate dosimetry for 90Y-2IT-BAD-Lym-1. Methods: Thirteen patients with advanced-stage NHL were given a preload dose of unmodified Lym-1 followed by an imaging dose of 111In-2IT-BAD-Lym-1. Sequential imaging and blood and urine samples obtained for up to 10 d after infusion were used to assess pharmacokinetics. Using 111In pharmacokinetic data and 90Y physical constants, radiation dosimetry for 90Y-2IT-BAD-Lym-1 was determined. Results: The uptake of 111In-2IT-BAD-Lym-1 in tumors was greater than uptakes in the lung and kidney but similar to uptakes in the liver and spleen. The biologic half-time in tumors was greater than in lungs. The mean radiation dose to tumors was 6.57 ± 3.18 Gy/GBq. The mean tumor-to-marrow (from blood) radiation ratio was 66:1, tumor-to-total body was 13:1, and tumor-to-liver was 1:1. Images of 111In were of excellent quality; tumors and normal organs were readily identified. Mild and transient Lym-1 toxicity occurred in 3 patients. Conclusion: Because of the long residence time of 111In-2IT-BAD-Lym-1 in tumors, high 90Y therapeutic ratios (tumor-to-tissue radiation dose) were achieved for some tissues, but the liver also showed high uptake and retention of the radiometal.
Key Words: antibody • radioimmunotherapy • radiation dosimetry • pharmacokinetics • 90Y
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