I-131-Lym-1 in mice implanted with human Burkitt's lymphoma (Raji) tumors:Loss of tumor specificity due to radiolysis

Preliminary evaluations of I-125-labeled Lym-1, an anti-lymphoma mouse IgG, monoclonal antibody, demonstrated favorable tumor uptake in mice bearing h uman Burkitt's lymphoma (Raji) tumors. In this study, the pharmacokinetics of I-125- and I-131-Lym-1, and the dosimetry, efficacy, and toxicity of I-1 31-Lym-1 in Raji-tumored mice were evaluated. Methods: Lym-1 was radioiodin ated by the chloramine-T method and analyzed for monomeric fraction and imm unoreactivity (antigen cell binding, relative to unmodified Lym-1). Nude mi ce bearing Raji tumors (20-500 mm(3)) received 1.5 MBq (40 mu Ci) I-125-Lym -1, or 1.5, 7.4, 14.8 or 18.5 MBq (40, 200, 400 or 500 mu Ci) I-131-Lym-1. Pharmacokinetic data (total body and blood clearance and biodistribution) w ere used to estimate radiation dosimetry. Mini-thermoluminescent dosimetry (TLD) was also used to measure radiation dosimetry directly for 7 days afte r injection of I-131-Lym-1. Tumor size, survival body weight, and blood cou nts were monitored for 60 days to evaluate therapeutic efficacy and toxicit y of I-131-Lym-1. Results. Al the time of injection the mean quality assura nce (QA) values for I-131-Lym-1 were 100% monomer and 100% relative immunor eactivity; the corresponding values for I-131-Lym-1 were 73% and 66%, indic ating that radiolysis had occurred during the interval between radiolabelin g and injection. I-125-Lym-1 exhibited high and sustained concentration in tumors relative to normal organs, whereas I-131-Lym-1 did not. Assuming ide ntical pharmacokinetic behavior to I-125-Lym-1, I-131-Lym-1 would deliver r adiation doses of 3.45, 0.83, 1.03, 0.34 and 0.56 Gy per MBq injected (12.8 , 3.1, 3.8, 1.3, and 2.1 rad/mu Ci), to tumor, liver, lungs, total body, an d marrow, respectively. When the actual pharmacokinetic data for I-131-Lym- 1 (1.5 MBq) were used to estimate dosimetry, corresponding values of 0.51, 0.72, 0.49, 0.31, and 0.41 Gy/MBq (1.9, 2.7, 1.8, 1.1, and 1.5 rad/mu Ci) w ere obtained. Similar values were obtained for mice receiving 7.4 or 14.8 M Bq of I-131-lym-1. Similarly, TLD data indicated little preferential radiat ion dosimetry to tumor. Response rates (cure + CR + PR) for mice receiving 0, 7.4, 14.8 and 18.5 MBq of I-131-lym-1 were 8% 7%, 21%, and 45%, respecti vely. The LD50/30 dose of I-131-Lym-1 was 12.7 MBq (343 mu Ci). Conclusions . I-125-Lym-1 exhibited high and sustained concentration in Raji tumors in mice, indicating excellent therapeutic potential for I-131-Lym-1. However, in vitro QA results for I-131-Lym-1 indicated that radiolysis had occurred and I-131-Lym-1 demonstrated little accumulation in tumor, or preferential radiation dosimetry to tumor in the same model.