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).
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 mm(3). 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, (131)I-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.
Spaeth
Nicolas
N
PET Center, Division of Nuclear Medicine, University Hospital Zurich, 8091 Zurich, Switzerland.
Wyss
Matthias T
MT
Pahnke
Jens
J
Biollaz
Gregoire
G
Trachsel
Eveline
E
Drandarov
Konstantin
K
Treyer
Valerie
V
Weber
Bruno
B
Neri
Dario
D
Buck
Alfred
A
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005240:Feasibility Studies; D005353:Fibronectins / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010865:Pilot Projects; D017434:Protein Structure, Tertiary; D016499:Radioimmunotherapy / Q000379:methods*; D011878:Radiotherapy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D000906:Antibodies; D005353:Fibronectins; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; C513931:SIP(L19) fusion protein