Synthesis and in vitro cellular uptake of 11C-labeled 5-aminolevulinic acid derivative to estimate the induced cellular accumulation of protoporphyrin IX

https://doi.org/10.1016/j.bmcl.2013.06.025Get rights and content

Abstract

Protoporphyrin IX (PpIX) accumulation induced by exogenous 5-aminolevulinic acid (ALA) in tumors affects the therapeutic efficacy of ALA-based photodynamic and sonodynamic therapies. To develop a new imaging probe to estimate the ALA-induced PpIX accumulation, 11C-labeled ALA analog (4), an ALA-dehydratase inhibitor, was radiosynthesized via 11C-methylation of a Schiff-base-activated precursor in the presence of tetrabutylammonium fluoride, followed by the hydrolysis of ester and imine groups. The cellular uptake of 4 linearly increased with time and was inhibited by ALA and other transporter competitors. Monitoring analog 4 with positron emission tomography might be useful to estimate the ALA-induced PpIX accumulation in tumors.

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Acknowledgments

We would like to thank the staff of the Cyclotron Operation and Radiochemistry sections for the production of the radioisotope, the technical support of the remote-controlled synthesis, and the identification of compounds by mass spectral analysis. This work was supported in part by KAKENHI23510289, 24591803, and 25861136.

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