Rhenium-186-labeled chimeric antibody NR-LU-13: pharmacokinetics, biodistribution and immunogenicity relative to murine analog NR-LU-10.
A mouse-human chimeric monoclonal antibody (NR-LU-13), with the same pancarcinoma antigen recognition site as a previously studied murine monoclonal antibody (NR-LU-10), was radiolabeled with 186Re using a bifunctional chelate. Nine patients (ages 31-81 yr) with metastatic adenocarcinoma received 186Re NR-LU-13. A single intravenous dose of 42 mg NR-LU-13 labeled with 25 mCi/m2 (two patients) or 60 mCi/m2 (seven patients) was administered. Mean serum disappearance half-time values for the chimeric 186Re NR-LU-10). Fifty percent of the radiolabel was excreted in the urine by 6 days. Tumor localization was demonstrated by gamma camera imaging in seven of nine patients. The percent injected dose per gram in a single tumor biopsy specimen was 0.003% at 72 hr postinjection. Absorbed dose to bone marrow was 1.5 +/- 0.7 rads/mCi and resulted in reversible myelosuppression in five of six evaluable patients who received 60 mCi/m2: median WBC nadir = 2500/microliters; median platelet nadir = 85,500/microliters. Low grade fever, nausea, slight elevations of liver function tests and mild allergic reactions were seen in some patients. The chimeric antibody elicited low levels of anti-NR-LU-13 antibody in six of eight evaluable patients (75%), in contrast to NR-LU-10 which elicited higher levels of human anti-mouse antibody in all patients. This pilot study demonstrates the ability of the chimeric antibody to target tumors with reduced (but not absent) immunogenicity and delayed clearance relative to the murine antibody.
Weiden
P L
PL
Department of Medicine, Virginia Mason Medical Center, Seattle, WA 98111.
Breitz
H B
HB
Seiler
C A
CA
Bjorn
M J
MJ
Ratliff
B A
BA
Mallett
R
R
Beaumier
P L
PL
Appelbaum
J W
JW
Fritzberg
A R
AR
Salk
D
D
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism*; D000912:Antibodies, Neoplasm / Q000276:immunology; D000917:Antibody Formation; D006207:Half-Life; D006801:Humans; D008875:Middle Aged; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics*; D012211:Rhenium / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D011868:Radioisotopes; D011993:Recombinant Fusion Proteins; D012211:Rhenium