Journal of Clinical Oncology, Vol 9, 548-564, Copyright © 1991 by American Society of Clinical Oncology
Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody
DM Goldenberg, JA Horowitz, RM Sharkey, TC Hall, S Murthy, H Goldenberg, RE Lee, R Stein, JA Siegel and DO Izon
Center for Molecular Medicine and Immunology, Newark, NJ 07103.
Sixteen patients with non-Hodgkin's lymphoma were infused with 6.2 to 58.2
mCi (0.2 to 3.9 mg) doses of radioactive iodine (131I)-labeled LL2
immunoglobulin G (IgG) or F(ab')2, in order to study antibody distribution,
pharmacokinetics, dosimetry, toxicity, tumor targeting, and therapy. LL2 is
a murine IgG2a monoclonal antibody (MAb) reactive with B cells and
non-Hodgkin's B-cell lymphoma. In a series of five assessable therapy
patients, doses as small as 30 mCi 131I-LL2 IgG or F(ab')2 resulted in
tumor responses (two partial remissions, two mixed and minor responses, and
one no response), while one patient receiving diagnostic doses as low as
6.2 mCi showed a partial remission for 1 year and a complete remission
after a second low radiation dose. No acute toxicities were noted, and only
myelotoxicity accompanied therapeutic doses, with grade IV marrow toxicity
seen in three of seven patients receiving total doses of about 50 mCi.
Dosimetry calculations showed spleen and tumor dose rules of about 4.6
cGy/mCi, which was three to four times the dose to other organs. Despite
the administration of relatively low doses of LL2 (0.2 to 3.9 mg), 82% of
60 known extrasplenic lymphoma sites were imaged. Serum clearance showed an
average distribution half-life (T1/2) of 2.1 hours and an elimination T1/2
of 32.0 hours. The average total-body clearance T1/2 was 43 to 45 hours.
LL2's antigenic target does not appear to be shed in high amounts into the
circulation. Three of eight patients having at least two injections showed
a human antimouse antibody response. These patients may have been
presensitized to animal protein. An interesting observation in this study
was the marked drop in circulating B lymphocytes after the administration
of radioiodinated LL2 or anticarcinoembryonic antigen MAbs, suggesting that
this is a nonspecific radiation effect and not necessarily related to the
binding of MAb to normal B cells.
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107(5):
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3(3):
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10(16):
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|
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|
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|
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|
|
|
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|
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|
|
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|
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|
|
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|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
|
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459 - 465.
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|
|
|
|
|
|
|
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July 14, 1993;
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230 - 232.
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[PDF]
|
|
|
|
