P16.31 * THERANOSTIC APPLICATION OF WATER-SOLUBLE GADOLINIUM FULLERENE (GD@FUL) IN EXPERIMENTAL GLIOMA MODEL

Abstract

Glioblastoma multiforme (GMB) is a highly invasive brain tumour with poor prognosis. Alternative treatments offering a better outcome are needed. Novel approach could be based on gadofullerenes that can be used as diagnostic MR imaging contrast agent and as a therapeutic drug. Water soluble gadofullerene Gd@Ful with composition Gd@C82(OH)x x ≥20 was synthesized for theranostic study. Nanosuspensions of Gd@Ful were used for magnetic relaxation measurements in vitro and for MR imaging of a rat with intracranially implanted C6 glioma. Gd@Ful was shown to reduce proton relaxation times in vitro, and provide dual contrast of T1- and T2-weighted images in a rat brain tumour model after paramagnetic intravenous delivery. Magnetic relaxation times and relaxivity of water protons under action of Gd@Ful were strongly shortened due to cluster formation and increase of motional correlation times of protons in the vicinity of the fulleren cage. The Gd@Ful administration promoted the improvement of glioma contrast enhancement at T2-weighted images due to accumulation of paramagnetic substance at the tumour site. The contrast efficiency of Gd@Ful corresponds to the characteristics of negative contrast agent. Retention of the Gd@Ful in the C6 glioma provides not only the tumor contrast enhancement but also has a high therapeutic relevance. We observed the increased survival rates in animals that were intravenously administered with Gd@Ful. Thus, in experimental group the survival was 75% higher then in the control group, constituting 34.2 ± 9.94 and 19.5 ± 3.02 days respectively (P < 0.001). The Gd@Ful solution is shown to be a contrast enhancer with high anti-tumour therapeutic potency.