Preloading with L-BPA, L-tyrosine and L-DOPA enhances the uptake of [F]FBPA in human and mouse tumour cell lines.

Aim of this study was to investigate if cellular [F]FBPA uptake can be increased upon preloading with amino acids. [F]FBPA uptake was assessed in HuH-7, CaCo-2 and B16-F1 cells pretreated with different concentrations or incubation times of L-BPA, L-tyrosine or L-DOPA. Without preloading, highest uptake of [F]FBPA was observed in B16-F1 cells, followed by CaCo-2 cells and HuH-7 cells.

Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6'-[F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia.

Positron emission tomography (PET) using fluorine-18 (F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6'-deoxy-6'-[F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12±8% (n=10, based on [F]fluoride starting activity) in a total synthesis time of 60min with a specific activity at end of synthesis of 218±58GBq/μmol (n=10).

The cell line NCl-H441 is a useful in vitro model for transport studies of human distal lung epithelial barrier.

The lack of a well characterized, continuously growing in vitro model of human distal lung epithelial phenotype constitutes a serious limitation in the area of inhalation biopharmaceutics, particularly in the context of transepithelial transport studies. Here, we investigated if a human lung adenocarcinoma cell line, NCl-H441, has potential to serve as an in vitro model of human distal lung epithelium. The development of barrier properties was studied by immunocytochemistry (ICC) against the junction proteins zonula occludens protein 1 (ZO-1) and E-cadherin and measurement of transepithelial electrical resistance (TEER).