TY - JOUR
T1 - In vitro and in vivo studies with [18F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor
AU - Nejjari, Mimoun
AU - Kryza, David
AU - Poncet, Gilles
AU - Roche, Colette
AU - Perek, Nathalie
AU - Chayvialle, Jean Alain
AU - Le Bars, Didier
AU - Scoazec, Jean Yves
AU - Janier, Marc
AU - Borson-Chazot, Françoise
N1 - Funding Information:
This work was supported by grants from Region Rhône-Alpes (Programme Thématiques Prioritaires Région), Cancéropole Lyon Auvergne Rhône-Alpes (CLARA) and Rhône-Alpes Genopole. We thank Mr. John Carew for the manuscript's English revision.
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Purpose: The aim of this study was to investigate (a) in vitro the relationship between [18F]fluorocholine ([18F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [18F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [18F]FCH and that of [18F]fluorodeoxyglucose ([18F]FDG) were measured before and after cytotoxic therapy. [18F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [18F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC50 values calculated with the [18F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [18F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [18F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [18F]FCH in liver metastases but there was a significant uptake of [18F]FDG. Conclusions: In vitro studies suggested that the incorporation of [18F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [18F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [18F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded.
AB - Purpose: The aim of this study was to investigate (a) in vitro the relationship between [18F]fluorocholine ([18F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [18F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [18F]FCH and that of [18F]fluorodeoxyglucose ([18F]FDG) were measured before and after cytotoxic therapy. [18F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [18F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC50 values calculated with the [18F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [18F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [18F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [18F]FCH in liver metastases but there was a significant uptake of [18F]FDG. Conclusions: In vitro studies suggested that the incorporation of [18F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [18F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [18F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded.
KW - Animal model
KW - Endocrine tumor
KW - Fluorocholine
KW - Fluorodeoxyglucose
KW - PET imaging
UR - http://www.scopus.com/inward/record.url?scp=37449025862&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2007.09.008
DO - 10.1016/j.nucmedbio.2007.09.008
M3 - Article
C2 - 18158951
AN - SCOPUS:37449025862
SN - 0969-8051
VL - 35
SP - 123
EP - 130
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 1
ER -