Efficacy Screening of Gloriosa Superba Extracts in a Murine Pancreatic Cancer Model Using (18)F-FDG PET/CT for Monitoring Treatment Response

Abstract

Purpose: In vivo efficacy of two herbal extracts of Gloriosa superba L. (Colchicaceae) was investigated in a murine pancreatic tumor model by tumor volume measurements and Positron Emission Tomography (PET) imaging using 2-deoxy-2-[(18)F]fluoro-d-glucose ((18)F-FDG).

Materials and methods: A crude extract of G. superba (GS) seeds rich in colchicine and a colchicine-poor extract (GS2B) containing mostly colchicoside as a putative prodrug were prepared. PANC02-bearing C57BL/6 mice were treated with either placebo, gemcitabine, or one of the extracts (three different doses) for 10 days. Tumor volume measurements were performed daily during treatment and additionally (18)F-FDG Positron emission tomography/computed tomography was acquired at baseline and after 7 days of treatment. Ki-67 and cleaved caspase-3 immunostaining was performed on the resected tumors.

Results: After 7 days of treatment, a dose-dependent tumor growth inhibition of both extracts was observed with the highest in vivo response at the highest dose of GS and GS2B and gemcitabine. A positive significant correlation was found between Ki-67 scores and relative tumor volumes (RTV), and a negative significant correlation between caspase-3 staining scores and RTV. A decrease in (18)F-FDG uptake was clearly observed in all treatment groups.

Conclusions: The therapeutic efficacy of the two different herbal extracts was demonstrated in an in vivo pancreatic tumor model. (18)F-FDG PET was able to detect an early response as overall lower (18)F-FDG uptake was measured in the treated groups.