标题：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
摘要：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 [125I] o -BON and [125I] 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, [125I] o -BON showed rapid clearance in comparison with [125I] m -BON. Selective interactions of [125I] o -BON and [125I] m -BON with sigma receptors on tumor cell membranes were confirmed by pretreatment experiments with various sigma and other receptor ligands. [125I] o -BON possesses higher specific binding toward sigma receptors than does [125I] m -BON; thus, [125I] o -BON was chosen for further evaluations. High uptake of [125I] o -BON was observed in various tumors, and a good linear correlation ( R 2=0.70) was found between accumulation of [125I] o -BON and the sigma receptor expression level. Furthermore, the accumulation of [125I] 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.
