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⁶⁷Cu- versus¹³¹I-Labeled Lym-1 Antibody: Comparative Pharmacokinetics and Dosimetry in Patients with Non-Hodgkin’s Lymphoma¹

Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California 95816 [G. L. D., D. L. K., S. S., D. A. D., S. J. D.], and Department of Chemistry, University of California, Davis, California 95616 [C. F. M.]

Antilymphoma mouse monoclonal antibody (MoAb) Lym-1, labeled with ⁶⁷Cu or ¹³¹I, has demonstrated promising results in radioimmunotherapy (RIT) for lymphoma. Although ¹³¹I has played a central role in RIT thus far, some properties of ⁶⁷Cu are preferable. A subset of our patients received both ⁶⁷Cu- and ¹³¹I-labeled Lym-1, allowing a comparative evaluation of the two radiopharmaceuticals administered to a matched population of patients. Four patients with B-lymphocytic non-Hodgkin’s lymphoma that had progressed despite standard therapy entered trials of ⁶⁷Cu- and ¹³¹I-labeled Lym-1, which were injected 3–26 days apart. Lym-1 was conjugated to 6-[p-(bromoacetamido)benzyl]-1,4,7,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (BAT) via 2-iminothiolane (2IT) and radiolabeled with ⁶⁷Cu to prepare ⁶⁷Cu-2IT-BAT-Lym-1; ¹³¹I-Lym-1 was preparred by the chloramine-T reaction. Planar imaging was used to quantitate ⁶⁷Cu-2IT-BAT-Lym-1 or ¹³¹I-Lym-1 in organs and tumors daily for 3 days or longer. ⁶⁷Cu-2IT-BAT-Lym-1 exhibited higher peak concentration in 92% (12 of 13) of tumors and a longer biological half-time in every tumor than ¹³¹I-Lym-1. The mean tumor concentration (%ID/g) of ⁶⁷Cu-2IT-BAT-Lym-1 was 1.7, 2.2, and 2.8 times that of ¹³¹I-Lym-1 at 0, 24, and 48 h after injection, respectively. The mean biological half-times of ⁶⁷Cu-2IT-BAT-Lym-1 and ¹³¹I-Lym-1 in tumor were 8.8 and 2.3 days, respectively. Consequently, the mean tumor radiation dose delivered by ⁶⁷Cu-2IT-BAT-Lym-1 was twice that of ¹³¹I-Lym-1, 2.8 (range 0.8–6.7), and 1.4 (range 0.4–3.5) Gy/GBq, respectively. ⁶⁷Cu-2IT-BAT-Lym-1 delivered a lower marrow radiation dose than ¹³¹I-Lym-1; hence, the tumor:marrow therapeutic indices were 29 and 9.7, respectively. Radiation doses from ⁶⁷Cu-2IT-BAT-Lym-1 and ¹³¹I-Lym-1 to normal tissues were similar except for liver, which received a higher dose from ⁶⁷Cu-2IT-BAT-Lym-1. Images obtained with ⁶⁷Cu-2IT-BAT-Lym-1 were superior. Radiation dosimetry data for ⁶⁷Cu-2IT-BAT-Lym-1 and ¹³¹I-Lym-1 agreed with corresponding data from the larger populations of patients from which the matched population for the current study was drawn. In conclusion, ⁶⁷Cu-2IT-BAT-Lym-1 given to non-Hodgkin’s lymphoma patients in close temporal proximity to ¹³¹I-Lym-1 exhibited greater uptake and longer retention in tumor, resulting in higher radiation dose and therapeutic index than ¹³¹I-Lym-1. These as well as other factors suggest that ⁶⁷Cu-2IT-BAT-Lym-1 may be superior to ¹³¹I-Lym-1 for RIT.

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