Biodistribution, pharmacokinetics and imaging of131I-labelled OC125 in ovarian cancer

Abstract

Fifteen patients with or suspected of having ovarian carcinoma were injected intravenously (i.v.) or intraperitoneally (i.p+) with t3tl-labelled OC 125 F(ab')z. Radioimmunoscintigraphy after i.v. injection revealed 50% of the tumor sites. After i.p. injection all tumor sites were visualized, except in one case in which the antibody remained loculated because of adhesions. One patient with endometrial cancer showed no specific uptake of the antibody after i.p. injection. The serum half-life of the radiolabelled antibody after i.v. injection was 30 hr. After i.p. injection there was a slow appearance of radiolabelled antibody in the blood with a maximum level of 1.4% dose per liter at 24 hr after injection. Urinary excretion of the radiolabel was the same for both routes of administration, with 50% of the dose excreted in approximately 48 hr. Tumor uptake was slightly higher after i.p. injection. Liver and bone marrow uptake after i.p. injection were one-half of the uptake after i.v. injection.Many epithelial ovarian cancers express tumor associated antigens which can be used as targets for imaging (Epenetos et al., 1982; Granowska et al., 1984) or therapy (Epenetos et al., 1986~). One of these markers, CA125, is expressed in more than 80% of these tumors (Kabawat et al., 1983). The antigen can be detected in the serum of ovarian carcinoma patients using a radioimmunometric assay and monoclonal antibody (MAb) OC 125 . A study was undertaken in which patients previously diagnosed with or suspected of having ovarian cancer were injected either intravenously or intraperitoneally with 1311-labelled F(ab')2 fragments of MAb OC125. Patients were scanned at different time intervals after injection. Blood and urine samples were used for pharmacokinetic studies and biopsy specimens were compared for the expression of OC125 antigen and uptake of antibody. PATIENTS AND METHODS PatientsFifteen patients with either a pelvic mass suspected to be ovarian cancer or a confirmed tissue diagnosis of ovarian cancer were entered in this study after informed consent was obtained. Most patients had a laparotomy scheduled 1-7 days after injection of the antibody. MAb OC125 was purified and F(ab')z fragments were prepared. The antibody was radioiodinated to a specific activity of approximately 2.5 mCi I3lI/mg protein (NEN, Boston, MA) (Haisma et al., 1986). The radiolabelled antibody preparation was proven to be apyrogenic and sterile. Immunoreactivity was determined (Lindmo et al., 1984) and found over 80% in all cases. AdministrationPatients received potassium iodide (SSKI, Upsher-Smith, Minneapolis, MN) 48 hr prior to and continuing for 4 days after injection of the antibody. The antibody dose ranged from 0.4 to 8.4 mg protein and the dose of 1311 ranged from 0.7 to 2.7 mCi. For intravenous injection the radiolabelled antibody was administered via a peripheral vein. Intraperitoneal injection was accomplished by diluting the antibody in 500 ml 0.9% saline solution and infusing the solution of antibody through an intra-abdominal catheter ...

Clinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer

“…The phase I and phase II trials have shown the potential of 131 I-labelled OC125 antigen-binding fragment as a therapeutic agent. 65–67 MUC4 is expressed by the tumour cells of peritoneal effusions in 99% of patients with ovarian cancer, indicating its potential as a target for intraperitoneal radioimmunotherapy. 53 …”

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

“…OC125 is a murine monoclonal antibody that recognizes the cell-surface antigen CA 125, a 1000-kDa glycoprotein (Hosono et al, 1992) expressed by 85% of non-mucinous epithelial ovarian cancers (Karlan et al, 1988). Conjugates of OC125 with radioisotopes (Haisma et al, 1988;Muto et al, 1992) and cytotoxic drugs (Beck et al, 1994) have been administered i.p. to target ovarian cancer in both animals and humans.…”

Radioimmunoscintigraphy of ovarian tumours with technetium-99m labelled monoclonal antibody-170: first clinical experiences

“…In addition the use of this promising MAb for diagnostic or therapeutic intraperitoneal applications and for radioimmunoguided surgery sho be investigated [19,[36][37][38][39][40][41].…”