Tritium labeled choline and fluoroethylcholine – In vitro evaluation for visualization of prostate cancer with PET

Abstract

1909

Objectives: Carbon-11 labeled choline (CH) showed great potential for imaging prostate cancer especially in correlation with modern imaging techniques as PET/CT [1, 2]. Due to longer half life and shorter positron range of ¹⁸F, resulting in higher resolution in PET, CH and the F-substituted analogue fluoroethylcholine (FEC) [3] were evaluated in in vitro investigations using [³H]CH and [³H]FEC.

Methods: Normal (human skin fibroblasts, HSF5 (A)) and tumor cells (prostate adenocarcinoma: bone metastasis, PC3 (B); prostate adenocarcinoma: brain metastasis DU145 (C)) were seeded 10⁵ cells/well on 6well plates and treated with 37 kBq/well of [³H]CH or [³H]FEC. After incubation cells were lysed by methanol incubation followed by liquid-liquid-extraction to elaborate lipophilic and hydrophilic metabolites [4]. Determination and quantification of free and phosphorylated substance in the hydrophilic fraction was analyzed by HPLC (for A and B).

Results: After 3 h of incubation the uptake of [³H]CH and [³H]FEC in tumor cells was significantly higher than in normal cells. Longer incubation up to 24 h confirmed the results (see table: Results calculated on 10⁶ cells in % dose, n > 3). In comparison to the distribution of [³H]CH metabolites the distribution of [³H]FEC metabolites led to similar amounts of activity in the hydrophilic fraction but less in the lipophilic fraction. [table] HPLC analysis showed same amounts of phosphorylation for [³H]CH and [³H]FEC in tumor cells B and C, but slower phosphorylation of both tracers in A.

Conclusions: With respect to longer half life and shorter positron range [¹⁸F]FEC seems to be a highly promising tracer for imaging prostate cancer with PET as similar results in cell experiments could be obtained using [³H]CH and [³H]FEC. Ref.: [1] Breeuwsma AJ et al., Eur. J. Nucl. Med. Mol. Imaging 2005, 32, 668-73. [2] Farsad M et al., J. Nucl. Med. 2005, 46, 1642-9. [3] Hara T et al., J. Nucl. Med. 2002, 43, 187-99. [4] DeGrado TR et al., J. Nucl. Med. 2001, 42, 1805-1814.