gms | German Medical Science

Objective: The Insulin-like growth factor (IGF) is known to play a major role in many human cancers. Overexpression of its receptor IGF-1 stimulates cell migration and proliferation in human gliomas in vitro. Thus the IGF-1 receptor is a potential target for anti-tumor therapies and this has been shown in a subcutaneous model using U87. We used an IGF-1 receptor antibody (IMC-A12) to inhibit glioblastoma growth in an orthotopic mouse model also using U87 in vivo and combined this with intracerebral intraparenchymal drug delivery.

Methods: Orthotopic xenografts were established in nude mice by using U87 glioblastoma cells. After one week osmotic minipumps were implanted in order to administer the IGF-1 receptor antibody directly into the tumor inoculation site over a period of three weeks. Subsequently the mice were sacrificed and tumorsize was analyzed histologically. Vessel density, proliferative activity and fraction of apoptotic tumor cells were determined immunohistochemically.

Results: Tumor growth was inhibited 75% by IMC-A12 in the U87 mouse model compared to controls, which is statistically highly significant (p<0.001). Mean tumor volume after three weeks of treatment was 3,53 mm³ and 14,04 mm³ in the controls respectively.

Conclusions: IMC-A12 administered as local intracerebral treatment can inhibit glioblastoma growth in an orthotopic xenograft model. Efficacious intraparenchymal delivery circumvents problems with blood brain barrier penetration, reduces the amount of drug to be used and minimizes potential systemic side effects. These results are to be confirmed in more invasively growing tumor models.