Phase I study of noninvasive imaging of adenovirus-mediated gene expression in the human prostate.
Phase I study of noninvasive imaging of adenovirus-mediated gene expression in the human prostate.
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DOI：
10.1038/mt.2008.172
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发表时间：
2008-10
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影响因子：
--
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中科院分区：
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--
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为了监测癌症的非侵入性潜在治疗性腺病毒，我们开发了一种基于钠碘转运体(NIS)的方法学。将携带两个自杀基因和NIS基因的复制型腺病毒Ad5-yCD/utTKSR39rep-hNIS注射到临床局限性前列腺癌患者的前列腺内。采用单光子发射计算机断层扫描(SPECT)技术，对感染细胞摄取Na99mTcO4的NIS基因表达(GE)进行无创性成像。研究治疗是安全的，98%的不良事件为1级或2级。在9例患者中，有7例(78%)在1×1012病毒颗粒(VP)时在前列腺中检测到GE，而在1×1011 VP时未检测到GE。用SPECT定量测定GE的体积和总量。在1 cm~3内注射1×1012 VP后，GE体积(GeV)增加到平均6.6 cm~3，平均占总前列腺体积的18%。腺病毒注射后1-2天，GEV和强度达到峰值，在前列腺中可检测到长达7天。全身成像显示基因在前列腺内表达，SPECT成像没有证据表明腺病毒在前列腺外扩散。结果表明，无创性显像腺病毒介导的基因治疗在人类是可行和安全的。
To monitor noninvasively potentially therapeutic adenoviruses for cancer, we have developed a methodology based on the sodium iodide symporter (NIS). Men with clinically localized prostate cancer were administered an intraprostatic injection of a replication-competent adenovirus, Ad5-yCD/utTKSR39rep-hNIS, armed with two suicide genes and the NIS gene. NIS gene expression (GE) was imaged noninvasively by uptake of Na99mTcO4 in infected cells using single photon emission–computed tomography (SPECT). The investigational therapy was safe with 98% of the adverse events being grade 1 or 2. GE was detected in the prostate in seven of nine (78%) patients at 1 × 1012 virus particles (vp) but not at 1 × 1011 vp. Volume and total amount of GE was quantified by SPECT. Following injection of 1 × 1012 vp in 1 cm3, GE volume (GEV) increased to a mean of 6.6 cm3, representing, on average, 18% of the total prostate volume. GEV and intensity peaked 1–2 days after the adenovirus injection and was detectable in the prostate up to 7 days. Whole-body imaging demonstrated intraprostatic gene expression, and there was no evidence of extraprostatic dissemination of the adenovirus by SPECT imaging. The results demonstrate that noninvasive imaging of adenovirus-mediated gene therapy in humans is feasible and safe.
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