Strategies for enhancement of radioimmunotherapy.
Two new strategies for increasing tumor uptake have been investigated. First the effect of interleukin-2 (IL-2) on tumor uptake of 125I-Lym-1 antibody in nude mice was investigated. Secondly, the use of 67Cu-labeled Lym-1 was evaluated in patients. In nude mice implanted with Raji human lymphoma, a greater than 2-fold enhancement of tumor uptake of 125I-Lym-1 was observed after administration of PEG-interleukin-2 (PEG-IL-2). The macrocycle 1,4,8,11-tetraazacylcotetradecane-N,N',N",N"'-tetraacetic acid (TETA), synthesized specifically for copper chelation, has been conjugated to Lym-1 for 67Cu labeling of the monoclonal antibody (MoAb). There was no evidence for bone or normal marrow uptake and the residence time in the tumor was prolonged. Surprisingly, a dose of 4.4 mCi that was intended for imaging induced substantial tumor regression in a patient.
DeNardo
G
G
Department of Internal Medicine, University of California Davis Medical Center, Sacramento 95816.
DeNardo
S
S
Kukis
D
D
Diril
H
H
Suey
C
C
Meares
C
C
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000000981:diagnostic imaging / Q000628:therapy; D002614:Chelating Agents / Q000494:pharmacology; D003301:Copper Radioisotopes; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011877:Radionuclide Imaging; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D007376:Interleukin-2; D007457:Iodine Radioisotopes; C063627:4-bromoacetamidobenzyl-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid