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


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.
1 Department of Pharmaceutical Sciences, Natural Products & Food Research and Analysis (NatuRA), University of Antwerp , Antwerp, Belgium .
Rica
R
Capistrano
2 Department of Nuclear Medicine, Antwerp University Hospital , Edegem, Belgium .|3 Molecular Imaging Center Antwerp (MICA), University of Antwerp , Antwerp, Belgium .
Christel
C
Vangestel
4 Center for Oncological Research (CORE), University of Antwerp , Antwerp, Belgium .
An
A
Wouters
3 Molecular Imaging Center Antwerp (MICA), University of Antwerp , Antwerp, Belgium .
Yanina
Y
Dockx
4 Center for Oncological Research (CORE), University of Antwerp , Antwerp, Belgium .
Patrick
P
Pauwels
2 Department of Nuclear Medicine, Antwerp University Hospital , Edegem, Belgium .|3 Molecular Imaging Center Antwerp (MICA), University of Antwerp , Antwerp, Belgium .
Sigrid
S
Stroobants
1 Department of Pharmaceutical Sciences, Natural Products & Food Research and Analysis (NatuRA), University of Antwerp , Antwerp, Belgium .
Sandra
S
Apers
4 Center for Oncological Research (CORE), University of Antwerp , Antwerp, Belgium .
Filip
F
Lardon
1 Department of Pharmaceutical Sciences, Natural Products & Food Research and Analysis (NatuRA), University of Antwerp , Antwerp, Belgium .
Luc
L
Pieters
3 Molecular Imaging Center Antwerp (MICA), University of Antwerp , Antwerp, Belgium .
Steven
S
Staelens
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D003078:Colchicine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D006801:Humans; D007124:Immunoenzyme Techniques; D019668:Liliaceae / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D023382:Toxicity Tests, Acute; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D010936:Plant Extracts; D019275:Radiopharmaceuticals; D003841:Deoxycytidine; D019788:Fluorodeoxyglucose F18; C014419:colchicoside; D003078:Colchicine; D000093542:Gemcitabine