In vitro and in vivo studies with [¹⁸F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor

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.