Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba 263-8555, Japan.
Bioorg Med Chem Lett. 2013 Aug 15;23(16):4567-70. doi: 10.1016/j.bmcl.2013.06.025. Epub 2013 Jun 20.
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, (11)C-labeled ALA analog (4), an ALA-dehydratase inhibitor, was radiosynthesized via (11)C-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.
原卟啉 IX（PpIX）在肿瘤中外源性 5-氨基酮戊酸（ALA）的积累影响了基于 ALA 的光动力和声动力疗法的治疗效果。为了开发一种新的成像探针来估计 ALA 诱导的 PpIX 积累，通过在四丁基氟化铵存在下对席夫碱激活的前体进行（11）C-甲基化，合成了放射性标记的 ALA 类似物（4），这是一种 ALA-脱水酶抑制剂，然后水解酯和亚胺基团。4 的细胞摄取随时间线性增加，并被 ALA 和其他转运体竞争物抑制。用正电子发射断层扫描监测类似物 4 可能有助于估计肿瘤中 ALA 诱导的 PpIX 积累。
