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; 125 I-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 afder 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 exprescion. The sensitivity for moRe advanced cancer and for recurRences was 10 percent. MoreOver, the in vivo tumor dargeting 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 ® ).
Similar content being viewed by others
References
Epenetos AA, Snook D, Durbin H, Johnson PM, Papadimitriou JT. Limitations of radiolabeled monoclonal antibodies for localization of human neoplasms. Cancer Res 1986;46:3183–91.
Doerr RJ, Abdel-Nabi H, Kragg D, Mitchell E. Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study. Ann Surg 1991;214:118–24.
Patt YZ, Lamki LM, Shanken J,et al. Imaging with indium-111-labeled anti-CEA monoclonal antibody ZCE-025 of recurrent colorectal or CEA-producing cancer in patients with rising serum CEA levels and occult metastases. J Clin Oncol 1990;8:1246–54.
Sikle-Santanello BJ, O'Dwyer PJ, Mojzisik C,et al. Radioimmunoguided surgery using the monoclonal antibody B72.3 in colorectal tumors. Dis Colon Rectum 1987;30:761–4.
Martin EW, Mojzisik C, Hinkle GH,et al. Radioimmunoguided surgery using monoclonal antibody. Am J Surg 1988;156:386–92.
Abdel-Nabi H, Doerr RJ. Radiolabeled monoclonal antibody imaging (immunoscintigraphy) of colorectal cancers: current status and future perspectives. Am J Surg 1992;163:448–56.
Stella M, De Nardi P, Paganelli G,et al. Surgery for colorectal cancer guided by radiodetecting probe. Clinical evaluation using monoclonal antibody B72.3. Eur J Surg 1991;157:485–8.
Scholm J, Colcher D, Roselli M,et al. Tumor targeting with monoclonal antibody B72.3. Nucl Med Biol 1989;16:137–42.
Thor A, Ouchi N, Szatack C. Distribution of oncofetal antigen tumor associated glycoprotein 72 defined by monoclonal antibody B72.3. Cancer Res 1986;46:3118–24.
O'Dwyer PJ, Mojzisik C, Hinkle G,et al. Intraoperative probe-directed radioimmuno-detection using a monoclonal antibody. Arch Surg 1986;121:1391–4.
Di Carlo V, Badellino F, Stella M,et al. Role of B72.3 125-I monoclonal antibody for colorectal cancer detection by radioimmunoguided surgery. Surgery (in press).
Sardi A, Workmann M, Mojzisik C,et al. Intra-abdominal recurrences of colorectal cancer detected by radioimmunoguided surgery (RIGS system). Arch Surg 1989;124:55–9.
Rowlinson G, Paganelli G, Snook D, Epenetos AA. Radiolocalisation of an anti-CEA monoclonal antibody (FO23C5) and its fragments in a colon carcinoma xenograft model. Int J Biol Markers 1988;3:259–64.
Sinitsyn VV, Mamontova AG, Checkneva YY, Shnyra AA, Domogatsky SP. Rapid blood clearance of biotinylated IgG after infusion of avidin. J Nucl Med 1989;30:66–9.
Green NM. Purification of avidin. Methods Enzymol 1970;18:414–7.
Becker WS, Saptogino A, Wolf FG. The single late 99-Tcn granulocyte antibody scan in inflammatory diseases. Nucl Med Commun 1992;13:186–92.
Mangili F, Stella M, Sassi I,et al. Localization of biotinylated monoclonal antibodies (B72.3 and FO23C5) in patients with colorectal cancer. Eur J Histochem 1993;37:53–7.
Paganelli G, Pervez S, Siccardi AG,et al. Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies. Int J Cancer 1990;45:1184–9.
Paganelli G, Magnani P, Zito F,et al. Three step monoclonal antibody tumor targeting in carcinoembryonic antigen positive patients. Cancer Res 1991;51:5960–6.
Colcher D, Keenan AM, Larson SM, Scholm J. Prolonged binding of a radiolabeled monoclonal antibody (B72.3) used for the in situ radioimmunodetection of human colon carcinoma xenograft. Cancer Res 1984;44:5744–51.
Sardi A, Siddiqi MA, Hinkle G, Mojzisik C, Martin EW. Localization by hand-held gamma probe of tumor labeled with antibody “cocktail.” J Surg Res 1989;47:227–34.
Siccardi AG, Buraggi GL, Callegaro L,et al. Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab)2 fragments of an Anti-CEA monoclonal antibody: a multicenter study. Cancer Res 1989;49:3095–103.
Goodwin DA, Meares CF, McCall MJ, McTigue M, Chaovapong W. Pretargeted immunoscintigraphy of murine tumors with indium-111 labeled bifunctional haptens. J Nucl Med 1988;29:226–34.
Paganelli G, Riva P, Deleide G,et al. In vivo labelling of biotinylated monoclonal antibodies by radioactive avidin: a strategy to increase tumor radiolocalization. Int J Cancer 1988;(Suppl 2):121–5.
Paganelli G, Stella M, De Nardi P,et al. A new method for faster blood clearance in radioimmunoguided surgery. J Nucl Biol Med 1990;35:88–9.
Stella M, De Nardi P, Paganelli G,et al. Nuove prospettive della chirurgia radioimmunoguidata: il sistema avidina-biotina. Ann Ital Chir 1991;62:231–4.
Benevento A, Dominioni L, Carcano G, Dionigi R. Radioimmunoguided surgery for resection of liver metastases. J R Coll Surg Edinb 1990;35:321–2.
Author information
Authors and Affiliations
Additional information
Supported by grant “Progetto Finalizzato C.N.R.-A.C.R.O.”
About this article
Cite this article
Stella, M., De Nardi, P., Paganelli, G. et al. Avidin-biotin system in Radioimmunoguided surgery for colorectal cancer. Dis Colon Rectum 37, 335–343 (1994). https://doi.org/10.1007/BF02053593
Issue Date:
DOI: https://doi.org/10.1007/BF02053593