Abstract
Radiolabeled GA-17, a murine monoclonal antibody that reacts specifically with glioma cells, bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in vivo. The affinity constant of GA-17 F (ab′)2 fragment binding to NCI-H69 was 1.02×108/M while that to the glioma cell line U87MG was 1.22×108/M. Iodine-125-labeled GA-17 F (ab′)2 fragments injected i.v. localized well in NCI-H69 cells xenografted in nude mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87±1.34%g−1 (mean±SD,n=5) 24 h after injection. On the other hand, control monoclonal F (ab′)2 fragments accumulated in the xenografted tumor at 0.75±0.30%g−1. The tumor-to-blood ratio was 1.8 for NCI-H69, while that of control F (ab′)2 was 0.60. In conclusion, the radiolabeled GA-17 F (ab′)2 fragment is expected to be useful clinically to visualize the small-cell lung cancer and in radioimmunotherapy.
Key words: Small-cell lung cancer, Scintigraphy, Monoclonal antibody
Abbreviations
- SCLC
small-cell lung cancer
- mAb
monoclonal antibody
References
- Abdel-Nabi HH, Schwartz AN, Higano CS, Wechter DG, Unger MW (1987) Colorectal carcinoma: detection with indium-111 anticarcinoembryonic-antigen monoclonal antibody ZCE-025. Radiology 164:617–621 [DOI] [PubMed] [Google Scholar]
- Carney DN, Gazdar AF, Bepler G, Nau M, Minna JD (1985) Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45:2913–2920 [PubMed] [Google Scholar]
- Chatal JF, Fumoleau P, Saccavini JC, Thedrez P, Curtet C, Bianco-Arco A, Chetanneau A, Peltier P, Kremer M, Guillard Y (1987) Immunoscintigraphy of recurrences of gynecologic carcinomas. J Nucl Med 28:1807–1819 [PubMed] [Google Scholar]
- Greenwood FC, Hunter WN, Glover JS (1963) The preparation of131I labeled human growth hormone of high specific radioactivity. Biochem J 89:114–123 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter WN, Greenwood FC (1962) Preparation of iodine-131 labeled human growth hormone of high specific activity. Nature 194:495–496 [DOI] [PubMed] [Google Scholar]
- Kalofonos HP, Pawlikowska TR, Hemingway N, Courtenay-Lack N, Dhokia B, Snook D, Sivolapenko GB, Hooker GR, McKenzie CG, Lavender PJ, Thomas DGT, Epenetos AA (1989) Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase. J Nucl Med 30:1636–1645 [PubMed] [Google Scholar]
- Kondo S, Miyatake S, Iwasaki K, Oda Y, Kikuchi H, Zu Y, Shamoto M, Namba Y (1992) Human glioma-specific antigens detected by monoclonal antibodies. J Neurosurg 30:506–511 [DOI] [PubMed] [Google Scholar]
- Larson SM (1985) Radiolabeled monoclonal anti-tumor antibodies in diagnosis and therapy. J Nucl Med 26:538–545 [PubMed] [Google Scholar]
- Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA Jr (1984) Determination of immunoreactive fraction of radiolabeled monoclonal antibody by linear extrapolation to binding at infinite antigen excess. J Immunol Methods 72:77–89 [DOI] [PubMed] [Google Scholar]
- Minna JD, Higgins GA, Glatstein EJ (1985) Cancer of the lung. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer; principle and practices of oncology, 2nd edn. Lippincott, Philadelphia, pp 507–597 [Google Scholar]
- Ponten J, Macintyre EH (1968) Long term culture of normal and neoplastic human glia. Acta Path Microbiol Scand 74:465–486 [DOI] [PubMed] [Google Scholar]
- Saga T, Endo K, Akiyama T, Sakahara H, Mitsuru K, Watanabe Y, Nakai T, Hosono M, Yamamoto T, Toyoshima K, Konishi J (1991) Scintigraphic detection of overexpressed c-erbB-2 protooncogene products by a class-switched murine anti-c-erbB-2 protein monoclonal antibody. Cancer Res 51:990–994 [PubMed] [Google Scholar]
- 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 28:342–348 [PubMed] [Google Scholar]
- Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann NY Acad Sci 51:660–672 [Google Scholar]
- Wakabayashi T, Yoshida J, Seo H, Kazo K, Murata Y, Matsui N, Kageyama N (1988) Characterization of neuroectodermal antigen by a monoclonal antibody and its application in CSF diagnosis of human glioma. J Neurosurg 68:449–455 [DOI] [PubMed] [Google Scholar]
