In a rat model of glioblastoma multiforme (GBM) (intracerebral implatation of human GBM cell lines in RNU rats), animals treated with daily injections of ACD-101 survived significantly longer than control animals providing evidence that clinically achievable doses have an antiproliferative effect also in vivo.

Using the same animal model, carrier added (c.a.) 131I-ACD-101 (a radiopharmaceutical preparation containing 131I-ACD-101 and ACD-101 in a defined quantitative relation), was shown to be superior to prolong survival compared to maximum tolerable external field radiation therapy (XRT).

Long-term surviving animals were sacrificed for further analysis. Histological work-up showed a complete disappearance of tumor tissue and normalisation of histochemical parameters of cerebral metabolism for animals treated with c.a. 131I-ACD-101. Previous tumor growth was clearly evidenced by signs of increased cerebral pressure (enlarged ventriculi), and substance defects at the tumor site. In contrast control animals died of cerebral pressure, which could clearly be ascribed to the histologically confirmed experimental gliomas. To our knowledge, these data provide the first evidence that established gliomas can be completely eradicated histologically rendering a curative treatment potentially possible. Further experiments in glioma-bearing RNU rats demonstrated that a combination of c.a. 131I-ACD-101 and XRT is able to afford a further improvement in survival compared to either therapy administered alone without negatively affecting tolerability.

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