Radioimmunotherapy in brain tumors

Gliomas and meningiomas are the most frequent primary brain tumors. Surgery, external beam radiotherapy, and chemotherapy are, at present, the essential components in the therapeutic management of malignant brain masses. Nevertheless, these methods present limitations in terms of clinical response and rate of toxicity and morbidity. Because of the need for complementary or alternative treatment modalities, brain tumor cells have been persistently investigated to determine the presence of specific antigens, with the goal of produceing antibodies that might be useful as therapeutics. An emerging approach is targeted radiotherapy, a strategy that utilizes a molecular vehicle (antibody or peptide) to selectively deliver cytotoxic radiation emitted by a radionuclide to malignant cell populations. Although many types of labeled molecules have been investigated for targeted cancer radiotherapy, trials in brain tumors have almost exclusively exploited the potential of radioimmunotherapy (RIT) by employing a radiolabeled monoclonal antibodies (MoAbs) as targeting vehicle. Recently, somatostatin receptors have been shown to be overexpressed in various brain tumors, especially meningiomas and glia-derived tumors. This evidence, following the clinical experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors, has suggested that somatostatin analogs, coupled with appropriate radioisotopes, might also be of value in the treatment of brain tumors. The most commonly used radionuclides in targeted radiotherapy are beta-emitters, specifically: Yttrium-90 (90Y), Iodine-131 (131I), and Lutetium-177 (177Lu). The differences in physical half-life, the presence or absence of gamma rays, the energy, and consequently, the range of beta-particles in tissue are important variables with respect to the radiation dose that can be delivered to the tumor. Although targeted radiotherapy models have been principally evaluated for systemic administration, RIT and PRRT may also be applied loco-regionally, in order to reduce systemic toxicity. This chapter describes systemic and intracavitary use of RIT in high grade glioma. A brief report on PRRT in meningioma is also included.