Cu-67-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma

Lym-1, a monoclonal antibody that preferentially targets malignant lymphocy tes, has induced therapeutic responses and prolonged survival in patients w ith non-Hodgkin's lymphoma when labeled with I-131. Radiometal-labeled anti bodies provide higher tumor radiation doses than corresponding I-131 antibo dies. Cu-67 has an exceptional combination of properties desirable for radi oimmunotherapy, including gamma and beta emissions for imaging and therapy, respectively, a biocompatible half-time and absence of pathways contributi ng to myelotoxicity. The radioimmunoconjugate, Cu-67-2IT-BAT-Lym-1, has bee n shown to be efficacious in nude mice bearing human Burkitt's lymphoma (Ra ji) xenografts. Based on these results, a clinical study of the pharmacokin etics and dosimetry of Cu-67-2IT-BAT-Lym-1 in patients with lymphoma was in itiated. Methods: Eleven patients with advanced stage 3 or 4 lymphoma were given a preload dose of unmodified Lym-1,then an imaging dose of 126-533 MB q (3.4-14.4 mCi) Cu-67-2IT-BAT-Lym-1. Total Lym-1 ranged from 25 to 70 mg d ependent on the specific activity of the radioimmunoconjugate and was infus ed at a rate of 0.5-1 mg/min. Imaging, physical examination, including cali per measurement of superficial tumors, and analysis of blood, urine and fec al samples were performed for a period of 6-13 d after infusion to assess p harmacokinetics, radiation dosimetry, toxicity and tumor regression. Result s: In 7 patients, in whom superficial tumors had been accurately measured, tumors regressed from 18% to 75% (mean 48%) within several days of Cu-67-2I T-BAT-Lym-1 infusion. The uptake and biological half-time of 67Cu-2IT-BATLy m-1 in tumors were greater than those of normal tissues, except the mean li ver half-time exceeded the mean tumor half-time. The mean tumor-to-marrow r adiation ratio was 32:1, tumor-to-total body was 24:1 and tumor-to-liver wa s 1.5:1. Images were of very good quality; tumors and normal organs were re adily identified. Mild and transient Lym-1 toxicity occurred in 6 patients; 1 patient developed a human antimouse antibody. There were no significant changes in blood counts or serum chemistries indicative of radiation toxici ty. Conclusion: Because of the long residence time of Cu-67-2IT-BATLym-1 in tumors, high therapeutic ratios were achieved and, remarkably, numerous tu mor regressions were observed after imaging doses. The results indicate con siderable therapeutic potential for Cu-67-2IT-BAT-Lym-1.