A Human-derived Dual MRI/PET Reporter Gene System with High Translational Potential for Cell Tracking.
A Human-derived Dual MRI/PET Reporter Gene System with High Translational Potential for Cell Tracking.
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DOI：
10.1007/s11307-021-01697-8
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发表时间：
2022-04
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
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作者：
报告基因成像已被广泛用于纵向报告移植工程细胞的全身分布和活力。多模式细胞跟踪可以提供关于细胞命运的补充信息。典型的多模式报告基因系统通常结合联合收割机临床和临床前模式。磁共振成像（MRI）和正电子发射断层扫描（PET），两种临床模式的多模式报告基因系统，将是有利的结合PET的灵敏度与MRI的高分辨率形态和非电离性质。我们开发并评估了由两个人源性报告基因组成的双MRI/PET报告基因系统，其利用临床报告探针进行工程细胞检测。作为概念验证，对乳腺癌细胞进行工程改造，使其共表达人有机阴离子转运蛋白多肽1B 3（OATP 1B 3）和人碘化钠同向转运蛋白（NIS），前者摄取临床MRI造影剂乙氧基苄基-二亚乙基三胺五乙酸钆（Gd-EOB-DTPA），后者摄取PET示踪剂[18 F]四氟硼酸盐（[18 F] TFB）。小鼠T1加权MRI结果显示，与对侧原始肿瘤相比，乳腺癌基因工程乳腺脂肪垫肿瘤的MRI信号显著更高（p < 0.05）。静脉或腹腔注射Gd-EOB-DTPA后5 h，对比增强无差异。在[18 F]TFB PET图像中，我们还发现工程肿瘤的标准摄取值（SUV）显著高于未处理肿瘤（p < 0.001）。与PET图像相比，在相对较高分辨率的MR图像中，肿瘤内信号增强的异质性更明显。我们的研究证明了非侵入性追踪使用我们的人源性双重MRI/PET报告系统设计的细胞的能力，从而能够对移植细胞进行更全面的评估。未来的工作重点是应用这种工具来跟踪治疗细胞，这可能有一天会使细胞跟踪在医疗保健系统中得到更广泛的应用。
Reporter gene imaging has been extensively used to longitudinally report on whole-body distribution and viability of transplanted engineered cells. Multi-modal cell tracking can provide complementary information on cell fate. Typical multi-modal reporter gene systems often combine clinical and preclinical modalities. A multi-modal reporter gene system for magnetic resonance imaging (MRI) and positron emission tomography (PET), two clinical modalities, would be advantageous by combining the sensitivity of PET with the high-resolution morphology and non-ionizing nature of MRI. We developed and evaluated a dual MRI/PET reporter gene system composed of two human-derived reporter genes that utilize clinical reporter probes for engineered cell detection. As a proof-of-concept, breast cancer cells were engineered to co-express the human organic anion transporter polypeptide 1B3 (OATP1B3) that uptakes the clinical MRI contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), and the human sodium iodide symporter (NIS) which uptakes the PET tracer, [18F] tetrafluoroborate ([18F] TFB). T1-weighted MRI results in mice exhibited significantly higher MRI signals in reporter-gene-engineered mammary fat pad tumors versus contralateral naïve tumors (p < 0.05). No differences in contrast enhancement were observed at 5 h after Gd-EOB-DTPA administration using either intravenous or intraperitoneal injection. We also found significantly higher standard uptake values (SUV) in engineered tumors in comparison to the naïve tumors in [18F]TFB PET images (p < 0.001). Intratumoral heterogeneity in signal enhancement was more conspicuous in relatively higher resolution MR images compared to PET images. Our study demonstrates the ability to noninvasively track cells engineered with our human-derived dual MRI/PET reporter system, enabling a more comprehensive evaluation of transplanted cells. Future work is focused on applying this tool to track therapeutic cells, which may one day enable the broader application of cell tracking within the healthcare system.
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影响因子：
3.7
作者：
Kim H;Cha GW;Jeong YE;Lee WG;Chang KS;Roh JY;Yang SC;Park MY;Park C;Shin EH
通讯作者：
Shin EH
影响因子：
3.7
作者：
Dubois, Veronica P.;Zotova, Darya;Ronald, John A.
通讯作者：
Ronald, John A.
影响因子：
9.3
作者：
Fruhwirth, Gilbert O.;Diocou, Seckou;Mullen, Greg E. D.
通讯作者：
Mullen, Greg E. D.
DOI：
10.1148/rycan.2019190035
发表时间：
2019-11-01
期刊：
RADIOLOGY-IMAGING CANCER
影响因子：
--
作者：
Nystrom, Nivin N.;Yip, Lawrence C. M.;Ronald, John A.
通讯作者：
Ronald, John A.
影响因子：
12.4
作者：
Parkins, Katie M.;Dubois, Veronica P.;Ronald, John A.
通讯作者：
Ronald, John A.