Efficacy of ruthenium coordination complex based Rutherrin in a pre-clinical rat glioblastoma (GBM) model (Conference Presentation)

Glioblastoma is a highly aggressive and common brain cancer in adults with a grave prognosis, and aggressive radio and chemotherapy provide only a 15 months median survival. We evaluated the tolerability, and efficacy of the Ruthenium-based photosensitizer TLD-1433 in the formulation with apo-Transferrin (Rutheriin®) in the RG2, rat glioblastoma model. The specific tumour uptake ratio, PDT threshold, of the RG2 rat glioblastoma models and normal brain in vivo were determined as well as the survival post-PDT and the extent of CD8+T cell infiltration post-PDT. Results were compared with those obtained by 5-ALA-induced PpIX mediated PDT in the same animal model. As both photosensitizers have different photophysical properties, the number of absorbed photons required to achieve an equal cell kill is compared during in-vitro and in vivo studies. A significantly lower absorbed energy was enough to achieve LD50 with Rutherrin® versus -PpIX mediated PDT. Rutherrin® provides higher selective uptake ratio (SUR>20) in RG2 tumours compared to normal brain, whereas the SUR for ALA-induced PpIX was 10.6 in the same tumour model. To evaluate the short-term tissue response in vivo enhanced T2-weighted MR images provided the spatial extent of edema, which is twice post PpIX-PDT versus Rutherrin®-PDT suggesting reduced non-specific damage typically associated with a secondary wave of neuronal damage. A significant survival increase was observed in Rutherrin® treated rats bearing RG2 versus PpIX-PDT for the selected treatment conditions, associated with an increased CD8+T cell infiltration in the tumours. Rutherrin®-PDT was well tolerated providing safe and effective treatment of RG2 -induced glioblastoma.