Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach

Abstract

The high-grade malignant gliomas (anaplastic astrocytomas and glioblastoma) have a very bad prognosis since the available methods of treatment (surgery, radiotherapy and chemotherapy) are unable to control the progression of the disease for long. The use of specific monoclonal antibodies labelled with a suitable isotope (iodine-131 or yttrium-90) represents an effective approach to hamper tumour regrowth. Some authors have injected the antibodies intravenously, or have tried to increase the tumour/background ratio with the avidin/biotin system. In many cases the labelled monoclonal antibodies were injected directly into the tumoral bed after the operation. The authors' experiences concern a quite large locoregional radioimmunotherapy study which was performed by using antitenascin antibodies labelled initially with 131I and more recently with 90Y. The clinical results demonstrate the ability of this technique to control, for a long time, the growth of these tumours. The glioblastoma median survival was prolonged to 25 months (131I group) or 31 months (90Y group). The response rate (which comprises PR, CR and NED) was 47.1% (glioblastoma 131I group) or 40% ( glioblastoma 90Y group). In many cases a significant tumour shrinking effect was radiologically demonstrated. The use of 90Y proved more favourable in bulky lesions, and reduced the radioprotection problems.

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

“…[8][9][10] As Nimotuzumab is an IGg1 humanized mAb, it could activate more efficiently immune effector cells in the tumor area than murine mAbs. 42 The visual inspection of the processed scintigraphic images and the biodistribution calculations revealed that 188 Re-Nimotuzumab was retained in tumour cavity and adjacent malignant tissues for a long period.…”

“…[6][7][8][9][10] The infusion of radiolabelled monoclonal antibodies directly into the postsurgical resection cavity has enabled the delivery of high radiation doses to the affected area without important harm to the surrounding normal brain tissue or distant organs.…”

Targeted radiotherapy of brain tumours

“…The maximum tolerated dose of 211 At-labelled chimeric 81C6 has yet to be defined. (Riva et al, 2000) have been evaluating the efficacy of 131 I-labelled and 90 Y-labelled BC-2 and BC-4 mAbs for the locoregional treatment of malignant gliomas. In these protocols, no distinction was made between the two mAbs.…”

“…A subsequent study was performed using 90 Y in order to investigate the potential effects of using a radionuclide emitting beta particles with greater tissue penetration (Riva et al, 2000). In this phase II investigation, 43 patients were treated, including six with anaplastic astrocytoma and 35 with glioblastoma.…”

Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy

“…20 As shown in phase II-III clinical trials, locoregional administration of radiolabeled antibody into surgical cavities following tumor resection has modestly improved survival. [21][22][23][24] However, many challenges exist to extend RIT to routine practice. For example, nonselective radiation to normal parenchyma, poor penetration of radiolabeled antibody into bulky tumors, and the complexity of the radiolabeling procedure remain as hurdles to the success of RIT in treating gliomas.…”