Biodistribution and intraoperative evaluation of radiolabeled monoclonal antibody MX35 in patients with epithelial ovarian cancer.
Murine monoclonal antibody (MAb) MX 35 shows strong homogeneous reactivity with more than 90% of epithelial ovarian cancers. Twenty-five patients with advanced ovarian cancer were entered into a clinical trial using 125I- or 131I-labeled MX 35 in doses of 2, 10, or 20 mg administered by intravenous (i.v.) or intraperitoneal injection. All patients underwent laparotomy at 7 to 20 days following MAb injection to assess tumor distribution, obtain biopsies of tumor and normal tissue, and evaluate the use of an intraoperative hand-held gamma-detecting device. Following i.v. injection, serum Mab half-life was 36 hr. Tumor biopsies obtained at surgery showed MAb accumulation of from 6.7 x 10(-3) to 4.0 x 10(-5)% injected dose/g of tissue. There was no correlation between absolute MAb accumulation in tumor and MAb dose administered. Regression analysis showed a correlation between MAb accumulation and the interval between MAb injection and surgery (P = 0.008). Specific localization of MAb in tumor was demonstrated by tumor:normal tissue ratios ranging from 2.3:1 to 34:1 (mean, 10.18:1). The tumor:normal tissue ratios were not significantly related to MAb dose, the level of immunohistochemical antigen expression, or the interval between MAb injection and surgery. Due to the relatively long serum half-life, mean tumor:serum ratios were only 1.53 following IV injection. This ratio did not correlate with MAb dose, days from injection, or antigen expression. There was an excellent correlation (P = 0.001) between MAb uptake, as measured by the intraoperative hand-held gamma counter, and direct gamma counting of excised tissues. MAb MX 35 localizes well to tumor in selected patients with ovarian cancer, and MAb uptake can be reliably quantitated in vivo with the hand-held intraoperative gamma counter.
Rubin
S C
SC
Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Kostakoglu
L
L
Divgi
C
C
Federici
M G
MG
Finstad
C L
CL
Lloyd
K O
KO
Larson
S M
SM
Hoskins
W J
WJ
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000601:surgery; D005260:Female; D006207:Half-Life; D006801:Humans; D007432:Intraoperative Period; D007457:Iodine Radioisotopes; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery; D016719:Radioimmunodetection / Q000379:methods*; D012044:Regression Analysis; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007457:Iodine Radioisotopes; C084424:MX 35 monoclonal antibody