Biodistribution of (111)indium-labeled engineered human antibody CTMO1 in ovarian cancer patients: influence of protein dose.
Thirty-one patients suspected of having ovarian cancer received a single i.v. injection of radiolabeled (100 MBq (111)In) engineered human CTMO1 (hCTMO1) to investigate its potential as an internalizing drug carrier. hCTMO1 is a complementary-determining region-grafted human IgG4 monoclonal antibody recognizing an ovarian carcinoma-associated antigen, the MUC-1-gene product. The amount of radioactivity was determined in tumor tissue, various normal tissues, including liver biopsies, and blood samples obtained at laparotomy, 6 days after injection of either 0.1 or 1.0 mg hCTMO1/kg of body weight. Circulating antigen-15-3 was measurable in all patients before injection, and immune complex formation was already present at the end of infusion. In the 0.1 mg/kg group, most of the radioactivity was bound to immune complexes, whereas in the 1.0 mg/kg group, most was bound to IgG monomers. Increasing the hCTMO1 dose 10-fold did not influence the overall disappearance of (111)In from the blood, but the elimination half-life of (111)indium bound to immune complexes was increased 2-fold. Uptake in tumor tissue 6 days postinjection at the 0.1 mg/kg dose was 7.6 times higher (P = 0.0009) than in normal tissue and 2.5 times higher (P = 0.03) than in blood. At the 1.0 mg/kg dose, the uptake in tumor tissue was 14.0 times higher (P = 0.0003) than in normal tissue and 8.1 times higher (P = 0.0007) than in blood. Liver activity was substantial (23.7 +/- 10.5 and 18.3 +/- 6.7% of the injected dose/kg for the 0.1 and 1.0 mg/kg dose group, respectively). These results are superior to those found with other clinically tested anti-MUC-1 gene product antibodies. hCTMO1 seems to be a suitable carrier for cytotoxic agents in ovarian carcinoma patients; the better uptake results and tumor-to-blood ratios are obtained at the higher dose of 1.0 mg hCTMO1/kg body weight.
van Hof
A C
AC
Department of Obstetrics and Gynecology, University Hospital Vrije Universiteit, Amsterdam, the Netherlands.
Molthoff
C F
CF
Davies
Q
Q
Perkins
A C
AC
Verheijen
R H
RH
Kenemans
P
P
den Hollander
W
W
Wilhelm
A J
AJ
Baker
T S
TS
Sopwith
M
M
Frier
M
M
Symonds
E M
EM
Roos
J C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D018396:Mucin-1