In vitro and in vivo studies with [(18)F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor.
OBJECTIVE
The aim of this study was to investigate (a) in vitro the relationship between [(18)F]fluorocholine ([(18)F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [(18)F]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 [(18)F]FCH and that of [(18)F]fluorodeoxyglucose ([(18)F]FDG) were measured before and after cytotoxic therapy. [(18)F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model.


RESULTS
The [(18)F]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 IC(50) values calculated with the [(18)F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [(18)F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [(18)F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [(18)F]FCH in liver metastases but there was a significant uptake of [(18)F]FDG.


CONCLUSIONS
In vitro studies suggested that the incorporation of [(18)F]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 [(18)F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [(18)F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded.
Nejjari
Mimoun
M
Hospices Civils de Lyon, Quai des Celestins, 69002 Lyon, France.
Kryza
David
D
Poncet
Gilles
G
Roche
Colette
C
Perek
Nathalie
N
Chayvialle
Jean-Alain
JA
Le Bars
Didier
D
Scoazec
Jean-Yves
JY
Janier
Marc
M
Borson-Chazot
Françoise
F
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism; D004067:Digestive System Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D004701:Endocrine Gland Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D051379:Mice; D009362:Neoplasm Metastasis; D011877:Radionuclide Imaging
D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; C514960:fluorocholine; D002794:Choline