Evaluation of prostate-specific membrane antigen as an imaging reporter.

Evaluation of prostate-specific membrane antigen as an imaging reporter.
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DOI:
10.2967/jnumed.113.134031
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发表时间:
2014-05
期刊:
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子:
--
通讯作者:
Pomper MG
Pomper MG
中科院分区:
其他
文献类型:
--
作者:
Castanares MA;Mukherjee A;Chowdhury WH;Liu M;Chen Y;Mease RC;Wang Y;Rodriguez R;Lupold SE;Pomper MG

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基因报告基因提供了一种非侵入性方法来监测和评估细胞群。基因报告-探针系统的理想特性包括生物相容性、缺乏免疫原性、低背景表达或信号以及高检测灵敏度。前列腺特异性膜抗原 (PSMA) 是一种有吸引力的基因报告候选者,因为它是一种具有选择性表达模式的人类跨膜蛋白,并且有多种 PSMA 显像剂可用于临床和临床前应用。我们通过与 2 种临床建立的报告基因(突变型单纯疱疹病毒 I 型胸苷激酶和人类碘化钠同向转运蛋白)进行比较,评估了 PSMA 作为基因成像报告基因的用途。构建表达每个报告基因的腺病毒并在体外验证其表达和功能。为了将 PSMA 与现有的成像报告基因进行比较,建立了双侧基质胶悬浮模型,其中裸鼠携带同样感染每种报告基因或对照腺病毒的细胞。进行动态 PET,并为每个报告基因-探针对生成时间-活性曲线。峰值目标与背景比率的比较表明,相对于对照基质胶悬浮液以及肌肉,PSMA 提供了最高的比率。此外,作为概念证明,PSMA 被用作成像报告基因,通过核成像探针和光学成像探针监测腺病毒肝转导。这些初步研究支持 PSMA 作为非侵入性基因报告基因的进一步发展。
Genetic reporters provide a noninvasive method to monitor and evaluate a population of cells. The ideal properties of a gene reporter-probe system include biocompatibility, lack of immunogenicity, low background expression or signal, and high sensitivity of detection. The prostate-specific membrane antigen (PSMA) is an attractive candidate for a genetic reporter as it is a human trans-membrane protein with a selective expression pattern, and there are several PSMA imaging agents available for clinical and preclinical applications. We evaluated the use of PSMA as a genetic imaging reporter by comparison to 2 clinically established reporters, the mutant herpes simplex virus type I thymidine kinase and the human sodium-iodide symporter. Adenoviruses expressing each reporter were constructed and validated in vitro for expression and function. To compare PSMA with existing imaging reporters, a bilateral Matrigel suspension model was established with nude mice bearing cells equally infected with each reporter or control adenovirus. Dynamic PET was performed, and time–activity curves were generated for each reporter-probe pair. A comparison of peak target-to-background ratios revealed that PSMA offered the highest ratio relative to the control Matrigel suspension as well as muscle. Further, as proof of concept, PSMA was applied as an imaging reporter to monitor adenoviral liver transduction with both nuclear and optical imaging probes. These preliminary studies support further development of PSMA as a noninvasive genetic reporter.
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