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Factors Affecting ¹³¹I-Lym-1 Pharmacokinetics and Radiation Dosimetry in Patients with Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia

University of California Davis Medical Center, Sacramento
University of California San Francisco, San Francisco, California
University of Alabama, Birmingham, Alabama

Correspondence: For correspondence or reprint contact: Gerald L. DeNardo, MD, Molecular Cancer Institute, 1508 Alhambra Blvd., Rm. 3100, Sacramento, CA 95816.

ABSTRACT

Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced therapeutic responses in patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) when labeled with ¹³¹I. Responders had statistically significant prolongation of survival compared with nonresponders. The nonmyeloablative, maximum tolerated dose for each of two doses of ¹³¹I-Lym-1 was 3.7 GBq/m² (total 7.4 GBq/m² [100 mCi/m2, total 200 mCi/m²]) of body surface area. The purpose of this study was to determine the pharmacokinetics and radiation dosimetry for the initial ¹³¹I-Lym therapy dose in patients with NHL and CLL and to compare tumor dosimetry with ¹³¹I-Lym-1 dosing and other patient parameters. Methods: Fifty-one patients with stage 3 or 4 lymphoma were treated with ¹³¹I-Lym-1 (1.74–8.04 GBq [20–217 mCi]) in either a maximum tolerated dose (MTD) or low-dose (LD) trial. Total Lym-1 given to each patient was sufficient in all instances to exceed the threshold required for stable pharmacokinetics. Quantitative imaging and physical examination, including caliper and CT measurement of tumor size and analysis of blood, urine and feces, were performed for a period of 7 to 10 d after infusion to assess pharmacokinetics and radiation dosimetry. Clinical records were reviewed to obtain data required for comparative assessments. Results: The concentration (%ID/g) and biologic half-time of ¹³¹I-Lym-1 in tumor were about twice those in normal tissues, although tumor half-time was similar to that of the thyroid. Pharmacokinetics were similar for patients in the MTD and LD trials, and for NHL and CLL patients in the LD trial, except that the latter group had less tumor concentration of ¹³¹1. Mean tumor radiation dose per unit of administered ¹³¹I was 1.0 Gy/GBq (3.7 rad/mCi) for patients with NHL whether in MTD or LD trials, about nine times greater than that for body or marrow. Tumor radiation dose was less and liver radiation dose was more in patients with CLL. Otherwise, radiation dosimetry was, on average, remarkably similar among groups of patients and among individual patients. Pharmacokinetics and dosimetry did not appear to be influenced by the amount of ¹³¹I or Lym-1 within the ranges administered. Tumor concentration of ¹³¹I and radiation dose per gigabecquerel were inversely related to tumor size but did not seem to be related to histologic grade or type, tumor burden or therapeutic response. Conclusion: The therapeutic index of ¹³¹I-Lym-1 was favorable, although the index for patients with CLL was less than that for patients with NHL. Pharmacokinetics and radiation dosimetry were, on average, remarkably similar among patients and groups of patients indifferent trials.

Key Words: antibody • radioimmunotherapy • ¹³¹I • dosimetry • cancer

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