ANTIBODY-RESPONSES TO MACROCYCLES IN LYMPHOMA

Metallic radioimmunoconjugates have promise for radioimmunoimaging and therapy. Macrocyclic chelating agents allow formation of stable metal lic radioimmunoconjugates but have been reported to be immunogenic. Th is study assesses human antibody responses in patients that were image d or treated with radiolabeled Lym-1 containing the macrocyclic chelat ors 1,4,8,11-tetraazacyclotetradecane-N,N',N '',N'''-tetraacetic acid (TETA) or 1,4,7,10-tetraazacyclododecane-N,N',N '',N'''-tetraacetic ac id (DOTA). Methods: One to six doses (median 1) and 6 to 285 mg (media n 33) Cu-67-2IT-BAT (2-iminothiolane bromoacetamidobenzyl TETA)- or In -111-2IT-BAD (2-iminothiolane bromoacetamidobenzyl DOTA)-Lym-1 were ad ministered to each of 18 patients with lymphocytic malignancies. Solid -phase ELISA, utilizing unchelated Lym-1 or human serum albumin conjug ated to DOTA, TETA or 1T-bromoacetamidobenzyl-ethylenediaminetetraacet ic acid (BABE) as coating antigens, was used to characterize antibody responses against Cu-67-2IT-BAT-Lym-1 and In-111-2IT-BAD-Lym-1 by quan titating antibodies against the Lym-1, DOTA, TETA or 2IT moieties, res pectively. Results: None of the patients had evidence for serum sickne ss. No patient that received In-111-2IT-BAD-Lym-1 developed antibodies to Lym-1 or DOTA. Two (15%) of the 13 patients that received Cu-67-2I T-BAT-Lym-1 developed antibodies against both TETA and Lym-1, and an a dditional patient developed antibodies against Lym-2 only. No patient developed an antibody response solely against the macrocycle, nor did any of the patients generate antibodies against the 2IT molecule. HAMA levels were many times greater in amount than HATA levels even when t heir relative molecular masses were considered. Conclusion: Although m acrocycles such as DOTA and TETA, and other chelates, can be haptens a nd thus potentially immunogenic, our findings do not support the view that macrocycles are more immunogenic than other radiometal chelating agents.