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,