Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients.
We describe a method to postlabel, in vivo, biotinylated monoclonal antibodies pretargeted onto tumor deposits when most of the non-tumor-bound antibodies have already been cleared as avidin-bound complexes. The application of this principle to tumor detection by immunoscintigraphy was tested in 20 patients with histologically documented cancer and increased circulating carcinoembryonic antigen levels. One mg of biotinylated anti-carcinoembryonic antigen monoclonal antibody (FO23C5) was administered i.v. (first step). After 3 days, 4-6 mg of cold avidin were injected i.v. (second step), followed 48 h later by 0.2-0.3 mg of a biotin derivative labeled with 111In (2-3 mCi) (third step). No evidence of toxicity was observed. Whole body radioactivity distribution was measured in five patients at various intervals postinjection by the conjugate counting technique. Tumors and metastases were detected in 18 of 19 patients (the remaining patient was a true negative) within 3 h after administration of 111In-biotin by planar or single photon emission tomography imaging. At the time of imaging, tumor/blood pool ratio was 5.5 +/- 3.2, and tumor/liver ratio was 6.7 +/- 3.9. Blood clearance of 111In-biotin was multiexponential, with the fast component having a t1/2 of 5 +/- 3 min. Urinary excretion of radioactivity over 3 h was 63.5 +/- 4.9% of the injected dose. Radioactivity at 3 h was 6.5 +/- 1.8% in blood, 1.6 +/- 0.3% in the kidney, and 2.4 +/- 0.6% in the liver. This approach represents an improvement in immunoscintigraphic techniques for tumor localization. The potential use for radioimmunotherapy is discussed.
Istituto Technologie Biomediche Avanzate-Consiglio Nazionale delle Ricerche, Università di Milano, Italy.
G
G
Paganelli
P
P
Magnani
F
F
Zito
E
E
Villa
F
F
Sudati
L
L
Lopalco
C
C
Rossetti
M
M
Malcovati
F
F
Chiolerio
E
E
Seccamani
D000911:Antibodies, Monoclonal / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007668:Kidney / Q000000981:diagnostic imaging; D008099:Liver / Q000000981:diagnostic imaging; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D009369:Neoplasms / Q000000981:diagnostic imaging*; D016719:Radioimmunodetection / Q000379:methods*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D007205:Indium Radioisotopes