Treatment of intracranial human glioblastoma by direct intratumoral administration of 131I‐labelled anti‐tenascin monoclonal antibody BC‐2

Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC‐2, raised against tenascin and labelled with 131I. Tenascin, the BC‐2‐recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti‐tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq of 131I) was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC‐2 uptake was 4.9% per gram and its effective half‐life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected 131I was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission (>50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after 11 months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection.

[1]  L. Zardi,et al.  Comparative analysis of the expression of the extracellular matrix protein tenascin in normal human fetal, adult and tumor tissues , 1991, International journal of cancer.

[2]  G. Casari,et al.  Human tenascin: primary structure, pre-mRNA splicing patterns and localization of the epitopes recognized by two monoclonal antibodies. , 1991, Nucleic acids research.

[3]  L. Zardi,et al.  Expression of tenascin and of the ED-B containing oncofetal fibronectin isoform in human cancer. , 1990, Cell differentiation and development : the official journal of the International Society of Developmental Biologists.

[4]  D. Bigner,et al.  Monoclonal antibody and F(ab')2 fragment delivery to tumor in patients with glioma: comparison of intracarotid and intravenous administration. , 1990, Cancer research.

[5]  D. Snook,et al.  Intraperitoneal radioimmunotherapy for ovarian cancer , 1990, British Journal of Obstetrics and Gynaecology.

[6]  F. Buchegger,et al.  Clinical value of immunoscintigraphy in colorectal carcinoma patients: a prospective study. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[7]  D. Stewart,et al.  The role of chemotherapy in the treatment of gliomas in adults. , 1989, Cancer treatment reviews.

[8]  R. Maxwell,et al.  Cerebral distribution of immunoconjugate after treatment for neoplastic meningitis using an intrathecal radiolabeled monoclonal antibody. , 1989, Neurosurgery.

[9]  R. Coleman,et al.  Pharmacokinetics and tumor localization of 131I-labeled anti-tenascin monoclonal antibody 81C6 in patients with gliomas and other intracranial malignancies. , 1989, Cancer research.

[10]  M. Sullivan,et al.  Intraperitoneal radioimmunotherapy for ovarian cancer , 1989 .

[11]  A. Ebner,et al.  Influence of anesthetics--nitrous oxide in particular--on electromyographic response evoked by transcranial electrical stimulation of the cortex. , 1989, Neurosurgery.

[12]  R. Klapdor,et al.  [Radioimmunotherapy of solitary liver metastases using intratumor instillation of 131I-labeled monoclonal antibodies--initial results of a clinical study]. , 1988, NuclearMedicine.

[13]  R. Coleman,et al.  Treatment of intracranial human glioma xenografts with 131I-labeled anti-tenascin monoclonal antibody 81C6. , 1988, Cancer research.

[14]  C. Patlak,et al.  Regional localization of a glioma-associated antigen defined by monoclonal antibody 81C6 in vivo: kinetics and implications for diagnosis and therapy. , 1987, Cancer research.

[15]  J. Taylor‐Papadimitriou,et al.  Limitations of radiolabeled monoclonal antibodies for localization of human neoplasms. , 1986, Cancer research.

[16]  D. Rogers,et al.  EGS4 code system , 1985 .

[17]  D. Schoenfeld,et al.  Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas . A joint radiation therapy oncology group and eastern cooperative oncology group study , 1983, Cancer.

[18]  H. Mellows,et al.  ROUTINE INDUCTION OF LABOUR WITH EXTRA‐AMNIOTIC PROSTAGLANDIN E2 IN A VISCOUS GEL , 1979, British journal of obstetrics and gynaecology.

[19]  D Riddoch,et al.  Neoplasms of the central nervous system. , 1977, The Practitioner.

[20]  M. Marangolo,et al.  Treatment of metastatic colorectal cancer by means of specific monoclonal antibodies conjugated with iodine-131: a phase II study. , 1991, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[21]  L. Zardi,et al.  Tenascin: A hexameric adhesive glycoprotein , 1989, International journal of cancer. Supplement = Journal international du cancer. Supplement.

[22]  M. Mariani,et al.  A simple qualitative determination of human antibodies to murine immunoglobulins (HAMA) in serum samples. , 1989, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[23]  M. Marangolo,et al.  Locoregional immunotherapy of human ovarian cancer: preliminary results. , 1989, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[24]  H. Erickson,et al.  Hexabrachion Protein (Tenascin, Cytotactin, Brachionectin) in Connective Tissues, Embryonic Brain, and Tumors , 1988 .

[25]  D. Rogers,et al.  Structure and Operation of the EGS4 Code System , 1988 .

[26]  P. Riva Radioimaging of Melanoma and CEA Secreting Tumours by Monoclonal Antibodies Performed by Different Routes of Administration , 1988 .

[27]  W. Rehpenning,et al.  Radioimmunbehandlung solitärer Lebermetastasen mittels intratumoraler Instillation 131J-markierter monoklonaler Antikörper - Erste Ergebnisse einer klinischen Studie , 1988, Nuklearmedizin.

[28]  G. Mariani,et al.  Immunoscintigraphy of colorectal carcinoma with F (ab')2 fragments of anti-CEA monoclonal antibody. , 1987, Cancer Detection and Prevention.

[29]  H. Atkins,et al.  Assessment of thyroid function and anatomy with technetium-99m as pertechnetate. , 1968, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  M Berman,et al.  A schema for absorbed-dose calculations for biologically-distributed radionuclides. , 1968, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.