Forsøksdyr: PL1 targeted imaging of glioblastoma

Godkjenningsdato 25.01.2018

Godkjenningsperiode 25.01.2018-01.04.2019

The current treatments against the brain tumor glioblastoma (GBM) are limited in efficacy, and the lacking effect results in poor patient prognosis. We are developing a novel glioblastoma-targeted therapy and a companion diagnostic compound that is highly tumor-selective. These are tumor-penetrating peptide-anticancer compound conjugates (PL1) that have the potential to improve the prognosis of affected patients in the future.
We have established animal models for studying both the targeting and the delivery effect of the peptide-conjugates. We use human GBM tumor cells that are injected either orthotopically or subcutaneously into nude mice. We will study the clinical application of PL1 by using small-animal PET/CT and MR as a method for identifying and diagnosing GBM.
Our overall aim is to develop a new method for GBM diagnoses and stratify patients for PL1-guided therapy.
The PL1 peptide-nanoparticle conjugates or the peptide alone do not cause any harm to the animals, as we have observed in our previous studies. Injections and imaging will cause mild harm to the animals, while tumor growth can cause moderate harm to the animals.
In total we will use 144 nude mice, and currently animal models are the only way to develop imagining- based diagnostic for GBM.
The animal models reflect 3D-structural behavior and physiological conditions that in vitro experiments cannot, and they are therefore not sufficient to obtain our aim.
The procedures will be carried out by at least two well-trained persons.
We will monitor the animals carefully after implantation of the tumor. We will follow the tumor growth by MRI, in addition to observation of the animals’ behavior, and measuring their body weight regularly. Animals will be euthanised when they develop symptoms identified by using a score sheet, or when the study reaches its endpoint.
Our research group have been working with GBM animal models for several years, which means we are well trained in performing these procedures. Therefore, the biological effect, human error and variation will be minimal and repetition of experiments will be unlikely.