COMPARATIVE TUMOR-LOCALIZATION OF WHOLE IMMUNOGLOBULIN-G ANTICARCINOEMBRYONIC ANTIGEN MONOCLONAL-ANTIBODIES IMMU-4 AND IMMU-4 F(AB')2 IN COLORECTAL-CANCER PATIENTS
Jl. Murray et al., COMPARATIVE TUMOR-LOCALIZATION OF WHOLE IMMUNOGLOBULIN-G ANTICARCINOEMBRYONIC ANTIGEN MONOCLONAL-ANTIBODIES IMMU-4 AND IMMU-4 F(AB')2 IN COLORECTAL-CANCER PATIENTS, Cancer, 73(3), 1994, pp. 850-857
Background, Previous studies in the literature have suggested that rad
iolabeled F(ab')(2) fragments might be superior to whole immunoglobuli
n G (IgG) for imaging and therapy of cancer because of their greater p
enetration in tumors. To test this hypothesis, the authors compared tu
mor and normal tissue uptake along with plasma clearance of I-125-labe
led monoclonal antibody (MoAb) IMMU-4 whole IgG with its I-131-labeled
F(ab')(2) fragment. Methods. Five patients with either liver metastas
es from colorectal cancer (n = 4) or intact primary tumors (n = 1) rec
eived a combination of I-125-IMMU-4 IgG (2 mCi/1 mg) plus I-131-IMMU-4
F(ab')(2) (10 mCi/1 mg) as a single 1-hour intravenous infusion on da
y 1. Serial blood samples were taken for up to 72 hours postinfusion t
o determine plasma clearance of each MoAb. On days 3-9, patients under
went exploratory laparotomy in which biopsies of tumor as well as norm
al 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 th
e 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 a
n RI greater than or equal to 3. There were no significant differences
in uptake (%ID/g) between F(ab')(2) and IgG (F[ab'](2) = 2.0 +/-: 0.5
7; IgG = 2.6 +/- 0.94). The mean +/- SD of plasma T1/2 was slightly sh
orter for F(ab')(2) (28.8 +/- 7.2 hours) than for IgG (45.9 +/- 16.7;
P = 0.08). Conclusion. In short, the biodistribution and pharmacokinet
ics of IMMU-4 F(ab')(2) were comparable to those of IMMU-4-IgG.