TORONTO, CanadaAn initial clinical trial with a new radionuclide has shown extended survival in patients with glioblastoma multiforme, the most common primary adult central nervous system tumor, according to data presented to the 48th Annual Meeting of the Society for Nuclear Medicine (abstract 454).
The study, carried out by Michael Zalutsky, PhD, and his colleagues at Duke University Medical Center, involved a series of modifications of a technique they had previously developed to administer a monoclonal antibody, chemically linked to a radionuclide, directly into the "resection cavity" created by surgical removal of most of the primary tumor.
The monoclonal antibody, 81C6, reacts with tenascin, an extracellular matrix glycoprotein that is expressed on more than 95% of brain tumors, with the level of expression increasing with the degree of malignancy. Thus, there is reason to anticipate that the antibody would preferentially bind to brain tumor cells.
In earlier work, the Duke group found that such preferential binding of the radioactively labeled antibody was indeed observed after intravenous administration. Unfortunately, however, the degree of localization to tumors was quantitatively insufficient, with the result that excessively high therapeutic doses would have been required to effect tumor cell killing.
Given that more than 90% of these tumors progress locally, with relatively low potential for systemic metastasis, Dr. Zalutsky’s group then opted for direct injection of the antibody into the resection cavity, with the hope that the enclosed space would permit the use of lower overall levels of radiation.
In their first attempt, a phase I study of patients with recurrent glioblastoma multiforme using an iodine-131-labeled antibody, median survival was 52 weeks, a significant improvement over the 16 to 24 weeks typically associated with this condition (Bigner D et al: J Clin Oncol 16:2202-2212, 1998).