Abstract
The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24–36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15–20 tnCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [99mTc]PnAO-bio-tin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1–2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.
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References
Kalofonos HP, Pawlikowska TR, Hemingway A, et al. Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase.J Nucl Med 1989;49:1636–1645.
Zalutsky MR, Moseley RP, Coakham HB, Coleman RE, Bigner DD. Pharmacokinetics and tumour localization of 131I-labeled anti-tenascin monoclonal antibody 81C6 in patients with gliomas and other intracranial malignancies.Cancer Res 1989;49:2807–2813.
Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD. Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody.Cancer Res 1983;43:2796–2805.
Epenetos AA, Snook D, Durbin H, Johnson PM, Papadimitriou JT. Limitations of radiolabelled monoclonal antibodies for localisation of human neoplasms.Cancer Res 1986;46:3183–3191.
Goodwin DA, Meares CF, McCall MJ, McTigue M, Chaovapong W. Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens.J Nucl Med 1988;29:226–234.
Paganelli G, Pervez S, Siccardi AG, Rowlinson G, Deleide G, Chiolerio F, Malcovati M, Scassellati GA, Epenetos AA. Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies.Int J Cancer 1990;45:1184–1189.
Kalofonos HP, Rusckowski M, Siebecker DA, Sivolapenko GB, Snook D, Lavender JP, Epenetos AA, Hnatowich DJ. Imaging of tumor in patients with indium-111-labeled biotin and streptavidin-conjugated antibodies: preliminary communicationJ Nucl Med 1990;31:1791–1796.
Paganelli G, Magnani P, Zito F, Villa E, Stella M, Lopalco L, Siccardi AG, Fazio F. Antibody guided tumor detection in CEA positive patients using the avidin-biotin system.Cancer Res 1991;51:5960–5966.
Natali PG, Zardi L. Tenascin: a hexameric adhesive glycoprotein.Int J Cancer 1989;Supp14:66–68.
Siri A, Carnemolla B, Saginati M, Leprini A, Casari G, Baralle F, Zardi I. Human tenascin: primary structure, pre-mRNA splicing patterns and localization of the epitopes recognized by two monoclonal antibodies.Nucleic Acids Res 1991;19:525–531.
Natali PG, Nicotra MR, Bigotti A, Bocca C, Castellani P, Russo AM, Zardi L. Comparative analysis of the expression of the extracellular matrix protein “tenascin” in human normal fetal, adult and transformed tissues.Int J Cancer 1991;47:811–816.
Koch P, Maecke HR.99mTc labeled biotin conjugate in a tumor pretargeting approach with monoclonal antibodies.Angervandte Chemie, Int. Edition, 1992;31:1507–1509.
Myres MJ, Lavender JP, De Oliveira GB, Maseri A. A simplified method of quantitated organ uptake using a gamma-camera,Br J Radiol 1981;54:1062–1067.
Seccamani E, Tattanelli M, Mariani M, Spranzi E, Scassellati GA, Siccardi AG. A simple qualitative determination of human antibodies to murine immunoglobulins (HAMA) in serum samples.Nucl Med Biol 1989;2:167–170.
Larson SM. Radiolabelled monoclonal anti-tumour antibodies in diagnosis and therapy.J Nucl Med 1985;26:538–545.
Le Doussal JM, Martin M, Gautherot E, Delaage M, Barber J. In vitro and in vivo targeting of radiolabeled monovalent and divalent haptens with dual specificity monoclonal antibody conjugates: enhanced divalent hapten affinity for cell-bound antibody conjugate.J Nucl Med 1989;30:1358–1366.
Hnatowich DJ, Virzi F, Rusckowski M. Investigations of avidin and biotin for imaging applications.J Nucl Med 1987;28:1294–1302.
Paganelli G, Malcovati M, Fazio F. Monoclonal antibody pretargetting techniques for tumour localization: the avidin-biotin system.Nucl Med Commun 1991;12:211–234.
Rubin RH, Fischam AJ, Callahan RJ, Knaw BA, Keech F, Ahmad M, Wilkinson R, Strauss W.111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection.N Engl J Med 1989;321:935–940.
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Paganelli, G., Magnani, P., Zito, F. et al. Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin. Eur J Nucl Med 21, 314–321 (1994). https://doi.org/10.1007/BF00947966
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DOI: https://doi.org/10.1007/BF00947966