Abstract
A murine monoclonal antibody MLS102 recognizes sialosyl-Tn antigen in mucin and immunohistochemically reacts with more than 80% of colorectal cancer tissues. The purpose of this study was to assess the usefulness of this monoclonal antibody for the immunoscintigraphy of colorectal cancer. Planar and SPECT images were obtained on day 2 or day 3 after injection of 2 mg and 74 MBq111In-labeled MLS102 antibody into 17 patients with colorectal cancer. Nine of 11 primary tumors and 4 of 6 locally recurrent tumors were detected. Positive images were obtained in all tumors larger than 4.5×2.7 cm. Three tumors of less than 2.5 cm and 1 recurrent tumor, which was missed by other imaging modalities, were negative. There were no adverse reactions. Human anti-(mouse Ig) antibody developed in 4 patients. Although improvement of detectability for smaller tumors needs to be pursued, the antibody MLS102 is potentially promising for use in immunoscintigraphy of colorectal cancer.
Similar content being viewed by others
References
Beatty JD, Duda RB, Williams LE, Sheibani K, Paxton RJ, beatty BG, Philben VJ, Werner JL, Shively JE, Vlahos WG, Kokal WA, Riihimaki DU, Terz JJ, Wagman LD (1986) Preoperative imaging of colorectal carcinoma with111In-labeled anticarcinoembryonic antigen monoclonal antibody. Cancer Res 46: 6494
Bischof-Delaloye A, Delaloye B, Buchegger F, Gilgien W, Studer A, Curchod S, Givel J-C, Mosimann F, Pettavel J, Mach J-P (1989) Clinical value of immunoscintigraphy in colorectal carcinoma patients: a prospective study. J Nucl Med 30: 1646
Brechbiel MW, Gansow OA, Atcher RW, Schlom J, Esteban J, Simpson DE, Colcher D (1986) Synthesis of 1-(p-isothiocyanatobenzyl) derivatives of DTPA and EDTA. Antibody labeling and tumor-imaging studies. Inorg Chem 25: 2772
Collier BD, Abdel-Nabi H, Doerr RJ, Harwood SJ, Olsen J, Kaplan EH, Winzelberg GG, Grossman SJ, Krag DN, Mitchell EP (1992) Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT. Radiology 185: 179
Deshpande SV, Subramanian R, McCall MJ, DeNardo SJ, DeNardo GL, Meares CF (1990) Metabolism of indium chelates attached to monoclonal antibody: minimal transchelation of indium from benzyl-EDTA chelate in vivo. J Nucl Med 31: 218
Divgi CR, McDermott K, Griffin TW, Johnson DK, Schnobrich KE, Fallone PS, Scott AM, Hilton S, Cohen AM, Larson SM (1993) Lesion-by-lesion comparison of computerized tomography and indium-111-labeled monoclonal antibody C110 radioimmunoscintigraphy in colorectal carcinoma: a multicenter trial. J Nucl Med 34: 1656
Fukui S, Horie T, Numata Y, Kitagawa H, Nakada H, Kawasaki T, Funakoshi I, Yamashina I (1991) Characterization of mucin antigens recognized by monoclonal antibodies raised against human colon cancer cells. Cancer Res 51: 331
Hnatowich DJ, Layne WW, Childs RL, Lanteigne D, Davis MA, Griffin TW, Doherty PW (1983) Radioactive labeling of antibody: a simple and efficient method. Science 220: 613
Itzkowitz SH, Yuan M, Montgomery CK, Kjeldsen T, Takahashi HK, Bigbee WL, Kim YS (1989) Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Res 49: 197
Kurosaka A, Kitagawa H, Fukui S, Numata Y, Nakada H, Funakoshi I, Kawasaki T, Ogawa T, Iijima H, Yamashina I (1988) A monoclonal antibody that recognizes a cluster of a disaccharide, NeuAca2→6GalNAc, in mucin-type glycoproteins. J Biol Chem 263: 8724
Lamki LM, Patt YZ, Rosenblum MG, Shanken LJ, Thompson LB, Schweighardt SA, Frincke JM, Murray JL (1990) Metastatic colorectal cancer: radioimmunoscintigraphy with a stabilized In-111-labeled F(ab′)2 fragment of an anti-CEA monoclonal antibody. Radiology 174: 147
Lamki LM, Buzdar AU, singletary SE, Rosenblum MG, Bhadkamkar V, Esparza L, Podoloff DA, Zukiwski A, Hortobagyi GN, Murray JL (1991) Indium-111-labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase I study. J Nucl Med 32: 1326
Lind P, Lechner P, Arian-Scad K, Gilgien W, Studer A, Curchod S, Givel J-C, Mosimann F, Pettavel J, Mach J-P (1991) Anti-carcinoembryonic antigen immunoscintigraphy (technetium-99m-monoclonal antibody BW 431/26) and serum CEA levels in patients with suspected primary and recurrent colorectal carcinoma. J Nucl Med 32: 1319
MacLean GD, Reddish M, Koganty RR, Wong T, Gandhi S, Smolenski M, Samuel J, Nabholtz JM, Longenecker BM (1993) Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. Cancer Immunol Immunother 36: 215
Murray JL, Rosenblum MG, Lamki L, Glenn HJ, Krizan Z, Hersh EM, Plager CE, Bartholomew RM, Unger MW, Carlo DJ (1987) Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody. ZME-018. J Nucl Med 28: 25
Ohshio G, Yoshioka H, Manabe T, Sakahara H, Yamabe H, Imamura M, Inoue M, Tanaka N, Nakada H, Yamashina I (1994) Expression of sialosyl-Tn antigen (monoclonal antibody MLS102 reactive) in normal tissues and malignant tumors of the digestive tract. J Cancer Res Clin Oncol 120: 325
Reynolds JC, Del Vecchio S, Sakahara H, Lora ME, Carrasquillo JA, Neumann RD, Larson SM (1989) Anti-murine antibody response to mouse monoclonal antibodies: clinical findings and implications. Nucl Med Biol 16: 121
Sakahara H, Endo K, Nakashima T, Koizumi M, Ohta H, Torizuka K, Furukawa T, Ohmomo Y, Yokoyama A, Okada K, Yoshida O, Nishi S (1985) Effect of DTPA conjugation on the antigen binding activity and biodistribution of monoclonal antibodies against alpha-fetoprotein. J Nucl Med 26: 750
Sakahara H, Endo K, Nakashima T, Koizumi M, Kunimatsu M, Kawamura Y, Ohta H, Nakamura t, Tanaka H, Kotoura Y, Yamamuro T, Hosoi S, Toyama S, Torizuka K (1987) Localization of human osteogenic sarcoma xenografts in nude mice by a monoclonal antibody labeled with radioiodine and indium-111. J Nucl Med 28: 342
Sakahara H, Onodera H, Kobayashi H, Yao Z, Yamashina I, Konishi J (1994) Reduced bone marrow uptake of111In-labeled monoclonal antibody after radiotherapy. Eur J Nucl Med 21: 1252
Schroff RW, Foon KA, Beatty SM, Oldham RK, Morgan AC Jr (1985) Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 45: 879
Schroff RW, Woodhouse CS, Foon KA, Oldham RK, Farrell MM, Klein RA, Morgan AC Jr (1985) Intratumor localization of monoclonal antibody in patients with melanoma treated with antibody to a 250,000-dalton melanoma associated antigen. J Natl Cancer Inst 74: 299
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sakahara, H., Onodera, H., Shirato, M. et al. Immunoscintigraphy of colorectal cancer using111In-labeled monoclonal antibody to mucin. Cancer Immunol Immunother 41, 157–161 (1995). https://doi.org/10.1007/BF01521341
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01521341