Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

Spaeth, Nicolas; Wyss, Matthias T.; Pahnke, Jens; Biollaz, Gregoire; Trachsel, Eveline; Drandarov, Konstantin; Treyer, Valerie; Weber, Bruno; Neri, Dario; Buck, Alfred

doi:10.1016/j.nucmedbio.2006.05.001

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 5 , Pages 661-666, July 2006

Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

Nicolas Spaeth
- PET Center, Division of Nuclear Medicine, University Hospital Zurich, 8091 Zurich, Switzerland
Matthias T. Wyss
- PET Center, Division of Nuclear Medicine, University Hospital Zurich, 8091 Zurich, Switzerland
Jens Pahnke
- Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland
- Department of Neurology, Rostock University, 18147 Rostock, Germany
Gregoire Biollaz
- Section of Clinical Immunology, University Hospital Zurich, 8091 Zurich, Switzerland
Eveline Trachsel
- Department of Applied Biosciences, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland
Konstantin Drandarov
- Center for Radiopharmaceutical Science of ETH, PSI and USZ, ETH Hoenggerberg Zurich and University Hospital Zurich, 8091 Zurich, Switzerland
Valerie Treyer
- PET Center, Division of Nuclear Medicine, University Hospital Zurich, 8091 Zurich, Switzerland
Bruno Weber
- PET Center, Division of Nuclear Medicine, University Hospital Zurich, 8091 Zurich, Switzerland
Dario Neri
- Department of Applied Biosciences, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland
Alfred Buck
- PET Center, Division of Nuclear Medicine, University Hospital Zurich, 8091 Zurich, Switzerland
- Corresponding author. Tel.: +41 44 255 35 47; fax: +41 44 255 44 14.

Received 23 March 2006; received in revised form 3 May 2006; accepted 8 May 2006.

Abstract

Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats.

Methods

C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220–360 MBq of iodine-131-labeled anti-EDB SIP(L19) (“small immunoprotein”) was administered intravenously into nine animals, yielding a radiation dose of 13–21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology.

Results

Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm³. When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P<.0176].

Conclusions

In this preliminary trial, ¹³¹I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies.

However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment.

Keywords: C6 glioma, Radioimmunotherapy, Angiogenesis, Extra domain B, Fibronectin