Comparative tumor localization of whole immunoglobulin G anticarcinoembryonic antigen monoclonal antibodies IMMU-4 and IMMU-4 F(ab')2 in colorectal cancer patients.
BACKGROUND
Previous studies in the literature have suggested that radiolabeled F(ab')2 fragments might be superior to whole immunoglobulin G (IgG) for imaging and therapy of cancer because of their greater penetration in tumors. To test this hypothesis, the authors compared tumor and normal tissue uptake along with plasma clearance of 125I-labeled monoclonal antibody (MoAb) IMMU-4 whole IgG with its 131I-labeled F(ab')2 fragment.


METHODS
Five patients with either liver metastases from colorectal cancer (n = 4) or intact primary tumors (n = 1) received a combination of 125I-IMMU-4 IgG (2 mCi/1 mg) plus 131I-IMMU-4 F(ab')2 (10 mCi/1 mg) as a single 1-hour intravenous infusion on day 1. Serial blood samples were taken for up to 72 hours postinfusion to determine plasma clearance of each MoAb. On days 3-9, patients underwent exploratory laparotomy in which biopsies of tumor as well as normal tissues (liver, normal colon, lymph node, and blood) were obtained. Tissues were weighed and counted in a gamma counter, and the percent of injected dose per kilogram (%ID/kg) of each antibody, along with the radiolocalization index (RI), was computed (RI = %ID/kg tumor.%ID/kg normal tissue).


RESULTS
Tumor uptake of both antibodies (2.3 +/- 0.53 %ID/kg) was significantly higher than that of normal tissues (0.56 +/- 0.12; P < 0.001), except for blood (2.8 +/- 0.83), resulting in an RI > or = 3. There were no significant differences in uptake (%ID/g) between F(ab')2 and IgG (F[ab']2 = 2.0 +/- 0.57; IgG = 2.6 +/- 0.94). The mean +/- SD of plasma T1/2 was slightly shorter for F(ab')2 (28.8 +/- 7.2 hours) than for IgG (45.9 +/- 16.7; P = 0.08).


CONCLUSIONS
In short, the biodistribution and pharmacokinetics of IMMU-4 F(ab')2 were comparable to those of IMMU-4-IgG.
Murray
J L
JL
University of Texas M.D. Anderson Cancer Center, Houston 77030.
Rosenblum
M G
MG
Zhang
H Z
HZ
Podoloff
D A
DA
Kasi
L P
LP
Curley
S A
SA
Chan
J C
JC
Roh
M
M
Hohn
D C
DC
Brewer
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001345:Autoradiography; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051379:Mice / Q000276:immunology; D010865:Pilot Projects; D016719:Radioimmunodetection
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; C081678:arcitumomab