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Biodistribution of ¹¹¹Indium-labeled Engineered Human Antibody CTMO1 in Ovarian Cancer Patients: Influence of Protein Dose

Departments of Obstetrics and Gynecology [A. C. v. H., C. F. M. M., R. H. M. V., P. K.], Nuclear Medicine [W. d. H., J. C. R.], and Pharmacy [A. J. W.], University Hospital Vrije Universiteit, 1007 MB Amsterdam, the Netherlands; Departments of Obstetrics and Gynecology [Q. D., E. M. S.] and Nuclear Medicine [M. F., A. C. P.], Queen's Medical Center, Nottingham, NG7 2UH, United Kingdom; and Celltech Therapeutics, Slough SL1 4EN, United Kingdom [T. S. B., M. S.]

Thirty-one patients suspected of having ovarian cancer received a single i.v. injection of radiolabeled (100 MBq ¹¹¹In) 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 ¹¹¹In from the blood, but the elimination half-life of ¹¹¹indium 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.

¹ To whom requests for reprints should be addressed.

Received 6/18/96. Accepted 9/16/96.

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