Avidin-biotin system in radioimmunoguided surgery for colorectal cancer. Advantages and limits

Abstract

Purpose: Radiolabeled monoclonal antibodies (MAbs) have been reported to allow tumor intraoperative detection by means of a gamma-detecting probe. The technology is called the Radioimmunoguided Surgery (RIGS) system. The main inconveniences of the method are 1) the long interval needed for clearance of unattached MAbs from the patient's body, between the injection of the MAb and surgery, and 2) the low sensitivity of current MAbs used in detecting small tumors. We describe a new method to overcome these inconveniences using biotinylated MAbs and avidin in order to obtain a rapid blood clearance of the radiolabeled MAbs both anticarcinoembryonic antigen and antitumor-associated glycoprotein-72 MAbs.

Methods: Twenty patients with primary and recurrent colorectal cancer have been enrolled in the study; 125I-biotinylated MAbs FO23C5 (anticarcinoembryonic antigen) and B72.3 (antitumor-associated glycoprotein-72) followed by cold avidin were injected in 13 patients and 7 patients, respectively.

Results: A decrease of 94 +/- 3 percent of circulating radioactivity was achieved in 3 to 5 days. Patients underwent surgery approximately seven days after MAb injections rather than after four weeks. Tumors were localized in 14/20 (70 percent) patients (true positive), 2 (10 percent) were false negative, and 4 (20 percent) were true negative. The overall sensitivity level in early-stage primary cancers was 37 percent when related to the presence of disease and 75 percent when related to antigenic expression. The sensitivity for more advanced cancer and for recurrences was 100 percent. Moreover, the in vivo tumor targeting of biotinylated MAb was demonstrated in frozen tumor section by direct streptoavidin-peroxidase staining.

Conclusions: The avidin-biotin system may enhance applicability and effectiveness of radioimmunoguided surgery (RIGS).