Human IgG responses to macrocyclic chelating agents (DOTA and TETA) in patients with B-lymphocytic malignancies
- 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-; ISSN 0161-5505; CNN: Grant NCI CA47829; TRN: 96:002093-0024
- Journal Information:
- Journal of Nuclear Medicine, Vol. 36, Issue Suppl.5; Conference: 42. annual meeting of the Society of Nuclear Medicine, Minneapolis, MN (United States), 12-15 Jun 1995; Other Information: PBD: May 1995
- Country of Publication:
- United States
- Language:
- English
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