Human IgG responses to macrocyclic chelating agents (DOTA and TETA) in patients with B-lymphocytic malignancies

Journal Article · Mon May 01 04:00:00 EDT 1995 · Journal of Nuclear Medicine

OSTI ID:441599

DeNardo, G L; Mirick, G R; Kroger, L A ^[1]

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1. Univ. of California-Davis, Sacramento, CA (United States); and others

Several metallic radionuclides have promise for immunoimaging and therapy. Macrocyclic chelating agents provide stable radioimmunoconjugates but have been reported to be immunogenic. The purpose of this study was to assess human antibody responses to macrocycles in 18 patients that were imaged and/or treated with In-111-21T-BAD-Lym-1 (5 patients) or Cu-67-21T-BAT-Lym-1 (13 patients) for B-lymphocytic malignancies. Lym-1 ranged from 1 to 6 doses (median 1) and from 6 to 285 mg (median 33) for each of the patients. A solid phase ELISA utilizing HSA-BAD, HSA-BAT, HSA-BABE or Lym-1 as the coating antigen was used to characterize and quantitate human antibodies in patient serum against DOTA, TETA, 21T or Lym-1, respectively. No patient that received In-111-21T-BAD-Lym-1 developed antibodies of any kind. Two (15%) of the 13 patients that received Cu-67-21T-BAT-Lym-1 developed antibodies against both TETA and Lym-1, and one additional patient developed antibodies against Lym-1 only. None of the patients had symptoms of serum sickness. The maximum number of doses of metal chelated Lym-1 without an immune response was 6. The smallest amount of TETA macrocycle that induced an anti-TETA response was 400 ug; the greatest amount of TETA that did not induce an anti-TETA response was 1,156 ug. The smallest amount of Lym-1 that induced a HAMA was 39 mg; the greatest amount of Lym-1 that did not induce a HAMA response was 285 mg. The relative amounts of anti-TETA to anti-Lym-1 were 1:30 and 1:95 in the two patients that developed both antibodies. None of the patients developed antibodies to the 2IT linker. Using different antibodies in patients with ovarian cancer, others have reported a high frequency of anti-macrocycle antibodies to DOTA. Although macrocycles such as DOTA and TETA can be haptens, our findings do not support the conclusion that they are more immunogenic than other radiometal chelating agents.

• DOE Contract Number: FG03-84ER60233
• OSTI ID: 441599
• Report Number(s): CONF-950603--; CNN: Grant NCI CA47829
• Journal Information: Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 36; ISSN 0161-5505; ISSN JNMEAQ
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANTIBODIES
BIOLOGICAL EFFECTS
CHELATING AGENTS
COPPER 67
DIAGNOSTIC TECHNIQUES
IMMUNITY
INDIUM 111
LABELLED COMPOUNDS
NEOPLASMS
PATIENTS
TETA