Efficacy and toxicity of 67Cu-2IT-BAT-Lym-1 radioimmunoconjugate in mice implanted with human Burkitt's lymphoma (Raji).
Radioimmunotherapy has shown promising results for treatment of radiosensitive malignancies such as lymphoma. Positive responses have been reported in patients with non-Hodgkin's lymphoma treated with 131I-radiolabeled Lym-1, a mouse anti-lymphoma monoclonal antibody. In this study, the efficacy of 67Cu-radiolabeled Lym-1 was examined. Nude mice bearing human Burkitt's lymphoma (Raji) tumors (20-524 mm3) were treated with 12.4, 14.8, 18.5, and 23.3 MBq of 67Cu-2IT-BAT-Lym-1. Tumor size was measured to assess efficacy, and mouse weight, blood counts, and mortality were monitored to assess toxicity. In mice treated with 12.4, 14.8, and 18.5 MBq of 67Cu-2IT-BAT-Lym-1, 50% (9 of 18), 42% (5 of 12), and 50% (3 of 6) of tumors achieved remission or cure; 33% of tumors were cured overall; and significant regrowth delay was observed. The 23.3 MBq dose group did not yield meaningful efficacy data because of high mortality. In control groups receiving 14.8 and 18.5 MBq of the isotype-matched nonspecific monoclonal antibody radioimmunoconjugate, 67Cu-2IT-BAT-L6, 0% (0 of 15) and 17% (2 of 12) of tumors achieved a response; hence, targeted delivery of radiation was the dominant antitumor mechanism of 67Cu-2IT-BAT-Lym-1. LD50/30 for mice treated with 67Cu-2IT-BAT-Lym-1 and -L6 were 21.6 and 20.6 MBq, respectively. In conclusion, 67Cu-2IT-BAT-Lym-1 provided a therapeutic and frequently curative dose of radiation to tumored mice with modest toxicity.
DeNardo
G L
GL
Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California 95816, USA.
Kukis
D L
DL
Shen
S
S
Mausner
L F
LF
Meares
C F
CF
Srivastava
S C
SC
Miers
L A
LA
DeNardo
S J
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D001772:Blood Cell Count / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D015431:Weight Loss / Q000187:drug effects
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D018796:Immunoconjugates; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C097568:copper-67-2IT-BAT-Lym-1