title: Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma.
abstract: Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced activation of receptor tyrosine kinase and cell proliferation. The effect of MAb 225 was studied in a phase I trial in patients with inoperable squamous cell carcinoma of the lung, which invariably expresses high levels of EGF receptors. Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300 mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (111In)-labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who received doses of 20 mg or greater. Presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon-emission-computed tomography could be carried out at the 120-mg and 300-mg doses and significantly improved tumor visualization. All patients produced anti-murine antibodies. We conclude that treatment with an MAb that inhibits EGF receptor function is safe at the doses and schedule studied. 111In-labeled MAb images squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent. Further studies are warranted to explore the potential therapeutic efficacy of anti-EGF receptor MAbs and other agents that act in a comparable manner.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: C R
authors.initials: CR
authors.lastname: Divgi
authors.forename: S
authors.initials: S
authors.lastname: Welt
authors.forename: M
authors.initials: M
authors.lastname: Kris
authors.forename: F X
authors.initials: FX
authors.lastname: Real
authors.forename: S D
authors.initials: SD
authors.lastname: Yeh
authors.forename: R
authors.initials: R
authors.lastname: Gralla
authors.forename: B
authors.initials: B
authors.lastname: Merchant
authors.forename: S
authors.initials: S
authors.lastname: Schweighart
authors.forename: M
authors.initials: M
authors.lastname: Unger
authors.forename: S M
authors.initials: SM
authors.lastname: Larson
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008099:Liver / Q000378:metabolism; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014055:Tomography, Emission-Computed
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D066246:ErbB Receptors