Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. He...Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen （PSMA） promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer （CRPC）. The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS （Ad.PSMApro-hNIS） or adenovirus.cytomegalovirus-hNIS containing the cytomegalovirus promoter （Ad.CMM-hNIS） or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus （Ad.CMV） infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells （P 〈 0.05）. An in vivo animal model showed a significant difference in 1311 radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus （P 〈 0.05） and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.展开更多
目的评估PSMA-PET/CT在接受新辅助治疗的寡转移前列腺癌患者中诊断及预后预测效能。方法回顾性纳入初治寡转移前列腺癌男性患者共50名,所有患者在基线时接受PSMA-PET/CT检查和其他评估,并接受4~6周期新辅助内分泌治疗合并化疗后,全麻下...目的评估PSMA-PET/CT在接受新辅助治疗的寡转移前列腺癌患者中诊断及预后预测效能。方法回顾性纳入初治寡转移前列腺癌男性患者共50名,所有患者在基线时接受PSMA-PET/CT检查和其他评估,并接受4~6周期新辅助内分泌治疗合并化疗后,全麻下行机器人辅助下前列腺癌根治术加盆腔淋巴结清扫术,术后患者继续接受内分泌治疗。计算并比较PSMA-PET/CT成像特征与其他临床特征的关系,使用Logistic回归分析各临床因素对预后的影响。结果PSA各水平组和各ISUP评分组间的SUVmax无显著差异;转移局限于盆腔组与出现盆腔外转移患者的SUVmax水平具有显著差异(21.01 vs 47.06,P=0.0059);单因素Logistic回归显示,SUVmax(OR=1.032,95%CI=1.002~1.063,P=0.040)和PSMA-PET/CT发现转移病灶是否位于盆腔范围内(OR=5.630,95%CI=1.648~19.232,P=0.006)与预后显著相关;多因素Logistic回归显示,PSMA-PET/CT发现转移病灶是否位于盆腔范围内(OR=3.879,95%CI=1.066~14.121,P=0.040)是预后预测的独立因素。结论PSMA-PET/CT能更准确估计转移范围,其成像结果也可以在一定程度上预测患者手术后的中短期预后。本文可为制定个性化精准化的治疗方案提供参考。展开更多
前列腺癌是威胁中老年男性生命健康的最常见的恶性肿瘤之一,其死亡率仅次于肺癌。前列腺特异性膜抗原(prostatic specific membrane antigen,PSMA)是一种前列腺癌细胞高表达的跨膜蛋白,是前列腺癌早期诊断、分期和治疗中的重要靶点。基...前列腺癌是威胁中老年男性生命健康的最常见的恶性肿瘤之一,其死亡率仅次于肺癌。前列腺特异性膜抗原(prostatic specific membrane antigen,PSMA)是一种前列腺癌细胞高表达的跨膜蛋白,是前列腺癌早期诊断、分期和治疗中的重要靶点。基于此,放射性核素标记的PSMA成为正电子发射型计算机断层显像(positron emission tomography,PET)的靶向分子探针,在前列腺癌患者的诊疗中具有独特的优势和重要的价值。本文总结了PSMA PET在前列腺癌临床诊疗中的应用进展,旨在更好服务于临床。展开更多
Using conventional imaging modalities, it is difficult to detect recurrent lesions in prostate cancer patients who have undergone biochemical relapse, especially in patients with low prostate-specific antigen （PSA） ...Using conventional imaging modalities, it is difficult to detect recurrent lesions in prostate cancer patients who have undergone biochemical relapse, especially in patients with low prostate-specific antigen （PSA） levels. We retrospectively reviewed the files of fifty patients with histopathologically confirmed prostate cancer who underwent 99mTc-labeled prostate-specific membrane antigen （PSMA） single-photon emission computed tomography （SPECT）/computed tomography （CT）, magnetic resonance imaging （MRI）, and bone scan within a 30-day period. PSMA-SPECT/CT indicated metastatic lesions in 39 patients and had a higher detection rate （78.0%） than bone scan （34.0%） or MRI （40.0%）. The diagnostic efficiency of PSMA-SPECT/CT imaging for bone and lymph node metastases （50.0% and 42.0%） was better than bone scan （34.0% and 0.0%） or MRI （24.0% and 20.0%）. PSMA-SPECT/CT provided a higher detection rate at serum PSA levels of 〈1 ng ml-1, 1-4 ng ml-1, 4-10 ng ml-1, and 〉10 ng ml-1. No correlation was found between Gleason score, PSA level, and the tracer tumor/background ratio of metastatic lesions. With the aid of PSMA-SPECT/CT imaging, the therapeutic strategy was changed for 31 patients, and this may have enhanced their clinical outcome. In conclusion, PSMA-SPECT/CT imaging could detect more metastatic lesions and achieve a higher detection rate than conventional imaging modalities at different serum PSA levels in prostate cancer patients who had undergone biochemical relapse.展开更多
文摘Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen （PSMA） promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer （CRPC）. The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS （Ad.PSMApro-hNIS） or adenovirus.cytomegalovirus-hNIS containing the cytomegalovirus promoter （Ad.CMM-hNIS） or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus （Ad.CMV） infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells （P 〈 0.05）. An in vivo animal model showed a significant difference in 1311 radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus （P 〈 0.05） and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.
文摘目的评估PSMA-PET/CT在接受新辅助治疗的寡转移前列腺癌患者中诊断及预后预测效能。方法回顾性纳入初治寡转移前列腺癌男性患者共50名,所有患者在基线时接受PSMA-PET/CT检查和其他评估,并接受4~6周期新辅助内分泌治疗合并化疗后,全麻下行机器人辅助下前列腺癌根治术加盆腔淋巴结清扫术,术后患者继续接受内分泌治疗。计算并比较PSMA-PET/CT成像特征与其他临床特征的关系,使用Logistic回归分析各临床因素对预后的影响。结果PSA各水平组和各ISUP评分组间的SUVmax无显著差异;转移局限于盆腔组与出现盆腔外转移患者的SUVmax水平具有显著差异(21.01 vs 47.06,P=0.0059);单因素Logistic回归显示,SUVmax(OR=1.032,95%CI=1.002~1.063,P=0.040)和PSMA-PET/CT发现转移病灶是否位于盆腔范围内(OR=5.630,95%CI=1.648~19.232,P=0.006)与预后显著相关;多因素Logistic回归显示,PSMA-PET/CT发现转移病灶是否位于盆腔范围内(OR=3.879,95%CI=1.066~14.121,P=0.040)是预后预测的独立因素。结论PSMA-PET/CT能更准确估计转移范围,其成像结果也可以在一定程度上预测患者手术后的中短期预后。本文可为制定个性化精准化的治疗方案提供参考。
文摘Using conventional imaging modalities, it is difficult to detect recurrent lesions in prostate cancer patients who have undergone biochemical relapse, especially in patients with low prostate-specific antigen （PSA） levels. We retrospectively reviewed the files of fifty patients with histopathologically confirmed prostate cancer who underwent 99mTc-labeled prostate-specific membrane antigen （PSMA） single-photon emission computed tomography （SPECT）/computed tomography （CT）, magnetic resonance imaging （MRI）, and bone scan within a 30-day period. PSMA-SPECT/CT indicated metastatic lesions in 39 patients and had a higher detection rate （78.0%） than bone scan （34.0%） or MRI （40.0%）. The diagnostic efficiency of PSMA-SPECT/CT imaging for bone and lymph node metastases （50.0% and 42.0%） was better than bone scan （34.0% and 0.0%） or MRI （24.0% and 20.0%）. PSMA-SPECT/CT provided a higher detection rate at serum PSA levels of 〈1 ng ml-1, 1-4 ng ml-1, 4-10 ng ml-1, and 〉10 ng ml-1. No correlation was found between Gleason score, PSA level, and the tracer tumor/background ratio of metastatic lesions. With the aid of PSMA-SPECT/CT imaging, the therapeutic strategy was changed for 31 patients, and this may have enhanced their clinical outcome. In conclusion, PSMA-SPECT/CT imaging could detect more metastatic lesions and achieve a higher detection rate than conventional imaging modalities at different serum PSA levels in prostate cancer patients who had undergone biochemical relapse.
