Evaluation of radioiodinated 1-[2-(3,4-Dimethoxyphenyl)ethyl]-4-(2-iodophenylpropyl)piperazine as a tumor diagnostic agent with functional sigma receptor imaging by single photon emission computed tomography.
Evaluation of radioiodinated 1-[2-(3,4-Dimethoxyphenyl)ethyl]-4-(2-iodophenylpropyl)piperazine as a tumor diagnostic agent with functional sigma receptor imaging by single photon emission computed tomography.
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DOI：
10.1248/bpb.31.879
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发表时间：
2008-05
影响因子：
2
通讯作者：
M. Hirata;Tetsuya Mori;T. Umeda;Takeshi Abe;Tomoya Yamamoto;Y. Ohmomo
中科院分区：
文献类型：
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作者：
M. Hirata;Tetsuya Mori;T. Umeda;Takeshi Abe;Tomoya Yamamoto;Y. Ohmomo
通过对sigma受体的可视化，评价了放射性碘化1-[2-（3,4-二甲氧基苯基）乙基]-4-（2-碘苯丙基）哌嗪（o-BON）和1-[2-（3,4-二甲氧基苯基）乙基]-4-（3-碘苯丙基）哌嗪（m-BON）作为单光子发射计算机断层扫描（SPECT）肿瘤显像的放射性药物。[125 I]o-BON和[125 I]m-BON在荷瘤小鼠体内的生物分布研究表明，放射性标记化合物在肿瘤中具有高的肿瘤摄取和长时间的滞留。与这些因素相比，血液和肌肉积累较低，导致肿瘤与血液和肿瘤与肌肉的比例较好。在外周器官中，与[125 I]m-BON相比，[125 I]o-BON表现出快速清除。[125 I]o-BON和[125 I]m-BON与肿瘤细胞膜上sigma受体的选择性相互作用通过各种sigma和其他受体配体的预处理实验得到证实。[125 I]o-BON比[125 I]m-BON对sigma受体具有更高的特异性结合；因此，[125 I]选择o-BON进行进一步评价。多种肿瘤均可见[125 I]o-BON的高摄取，且[125 I]o-BON的积累与sigma受体表达水平呈良好的线性相关（R2=0.70）。此外，[125 I]o-BON在肿瘤中的积累反映了肿瘤的增殖速度。这些结果表明，使用放射性碘化o-BON作为测量与sigma受体表达相关的增殖状态的标志物是可行的。
Radioiodinated 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(2-iodophenylpropyl)piperazine (o-BON) and 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-iodophenylpropyl)piperazine (m-BON) were evaluated as single photon emission computed tomography (SPECT) radiopharmaceuticals for tumor imaging by visualization of sigma receptors. In vivo biodistribution studies of [125 I]o-BON and [125 I]m-BON in tumor-bearing mice showed a high tumor uptake and prolonged retention of radiolabeled compounds in the tumor. In contrast with these factors, the blood and muscle accumulations were low, which resulted in a good tumor-to-blood ratio and tumor-to-muscle ratio. In peripheral organs, [125 I]o-BON showed rapid clearance in comparison with [125 I]m-BON. Selective interactions of [125 I]o-BON and [125 I]m-BON with sigma receptors on tumor cell membranes were confirmed by pretreatment experiments with various sigma and other receptor ligands. [125 I]o-BON possesses higher specific binding toward sigma receptors than does [125 I]m-BON; thus, [125 I]o-BON was chosen for further evaluations. High uptake of [125 I]o-BON was observed in various tumors, and a good linear correlation (R2=0.70) was found between accumulation of [125 I]o-BON and the sigma receptor expression level. Furthermore, the accumulation of [125 I]o-BON in tumors reflected their proliferation rate. These results suggest that it is feasible to use radioiodinated o-BON as a marker for measuring the proliferative status associated with sigma receptor expression.