Distribution of radiolabeled monoclonal antibody MX35 F(ab')2 in tissue samples by storage phosphor screen image analysis: evaluation of antibody localization to micrometastatic disease in epithelial ovarian cancer.
Our objective was to quantify the targeting of the monoclonal antibody (mAb) MX35 F(ab')2 to micrometastatic epithelial ovarian cancer. This mAb detects a Mr 95,000 glycoprotein with homogeneous distribution on 80% of ovarian tumor specimens. Six patients with minimal residual disease from an imaging trial were injected with 2 or 10 mg of 131I- and 125I-labeled mAb MX35 F(ab')2. Biopsied samples were removed at second-look laparotomy 1-5 days post-i.v. or -i.p. infusion of antibody. Serial cryostat sections were stained by indirect immunoperoxidase method for antigen distribution and exposed to storage phosphor screens for quantitative autoradiography. Coregistration of tumor histology, antigen expression, and radionuclide distribution demonstrated specific localization in micrometastatic tumor foci (50 micrometer to 1 mm) found within tissue stroma. The radiolabeled antibody uptake determined by well scintillation counts ranged between 5.2 and 223.5 x 10(-4) percentage of injected dose/g of tumor tissue for 131I. Specific localization of mAb in tumor was determined by tumor:normal tissue (fat) ratios ranging from 0.9:1 to 35.9:1 for 131I. The high resolution and linear response of the storage phosphor screen imager was used to estimate the radionuclide activity localized in each micrometastatic site. Quantitation of phosphor screen response revealed microCi/g values of 0.026-0.341 for normal tissue and 0.184-6.092 for tumor biopsies, evaluated 4 or 5 days post-antibody injection. The tumor:normal tissue (adjacent to tumor) ratios were between 1 and 4 times greater using the phosphor screen method than well counter measurements, but even larger variations of ratios up to 20:1 were observed between tumor cell foci and stromal cells within the same tissue section. This study has demonstrated that mAb MX35 F(ab')2 localizes to the micrometastatic ovarian carcinoma deposits within the peritoneal cavity. The dosimetry results suggest a therapeutic potential for this antibody in patients with minimal residual disease (<5 mm).
Finstad
C L
CL
Gynecology Service, Department of Surgery, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Lloyd
K O
KO
Federici
M G
MG
Divgi
C
C
Venkatraman
E
E
Barakat
R R
RR
Finn
R D
RD
Larson
S M
SM
Hoskins
W J
WJ
Humm
J L
JL
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D058846:Antibodies, Monoclonal, Murine-Derived; D001345:Autoradiography / Q000379:methods; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000556:secondary; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging*; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D011856:Radiographic Image Enhancement; D016719:Radioimmunodetection / Q000379:methods*; D014963:X-Ray Intensifying Screens
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007457:Iodine Radioisotopes; C084424:MX 35 monoclonal antibody