Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody.
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.
Goldenberg
D M
DM
Center for Molecular Medicine and Immunology, Newark, NJ 07103.
Horowitz
J A
JA
Sharkey
R M
RM
Hall
T C
TC
Murthy
S
S
Goldenberg
H
H
Lee
R E
RE
Stein
R
R
Siegel
J A
JA
Izon
D O
DO
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes