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基于 PSMA 表达,定量 [Fe]MRI 测定 PSMA 靶向 SPIONs 的动力学可区分前列腺肿瘤异种移植物。

Quantitative [Fe]MRI determination of the dynamics of PSMA-targeted SPIONs discriminates among prostate tumor xenografts based on their PSMA expression.

机构信息

Department of Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.

出版信息

J Magn Reson Imaging. 2018 Aug;48(2):469-481. doi: 10.1002/jmri.25935. Epub 2018 Jan 13.

DOI:10.1002/jmri.25935
PMID:29331081
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6045454/
Abstract

BACKGROUND

There is a need for a quantitative MRI method for iron concentration magnetic resonance imaging suitable for measuring the delivery of targeted superparamagnetic iron oxide nanoparticles (SPIONs) to tumors.

PURPOSE

To apply our newly developed [Fe]MRI method to the quantitative imaging in both space and time of the iron dynamics of anti-prostate specific membrane antigen (PSMA) conjugated SPIONs within human prostate tumor xenografts in nude mice.

STUDY TYPE

Longitudinal.

ANIMAL MODEL

45 Harlan Sprague Dawley athymic nude mice bearing xenografts from PSMA-positive LNCaP, C4-2 and PSMA-negative DU145 tumors from human prostate tumor cell lines.

FIELD STRENGTH/SEQUENCE: 1.0 Tesla/ T and T weighted spin echo.

ASSESSMENT

Image intensity and contrast measurements.

STATISTICAL TESTS

Student's t-test.

RESULTS

The SPION diffusion coefficient within tumors was D = 44.8 ± 2.4 × 10 mm /s. The iron taken up by PSMA-positive LNCaP and C4-2 tumors was proportional to the tail-vein injected dose from 60 nmol to 1.6 μmol; injection of 1 μmol of iron in anti-PSMA conjugated SPIONs resulted in a tumor [Fe] of 76 μM. Even at the highest iron dose of 1.6 μmol, the PSMA-negative DU145 tumors took up no significant iron from the anti-PSMA conjugated SPIONs. A similar lack of nonspecific uptake was observed when the antibodies against PSMA were omitted from the injected SPION preparation. The fraction of the initial iron dose that was taken up by PSMA-positive tumors was 2.32 ± 0.75% (n = 10); uptake by the PSMA-negative DU145 tumors and for SPIONs without anti-PSMA antibodies was 0.16 ± 0.34% (n = 7) giving a ratio of [Fe] in PSMA + versus PSMA- tumors greater than 15:1 (P = 0.01).

DATA CONCLUSION

Quantitative [Fe]MRI of anti-PSMA conjugated SPIONs discriminated between PSMA-positive LNCaP and C4-2 and PSMA-negative DU145 human prostate tumor xenografts in vivo.

LEVEL OF EVIDENCE

1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. J. MAGN. RESON. IMAGING 2018;48:469-481.

摘要

背景

需要一种适用于测量靶向超顺磁氧化铁纳米粒子 (SPION) 递送至肿瘤的铁浓度磁共振成像的定量 MRI 方法。

目的

应用我们新开发的 [Fe]MRI 方法,对荷有人前列腺肿瘤细胞系 PSMA 阳性 LNCaP、C4-2 和 PSMA 阴性 DU145 肿瘤的抗前列腺特异性膜抗原 (PSMA) 偶联 SPION 内铁动力学进行定量成像。

研究类型

纵向。

动物模型

45 只哈兰斯普拉格道利无胸腺裸鼠,携带源自 PSMA 阳性 LNCaP、C4-2 和 PSMA 阴性 DU145 人前列腺肿瘤细胞系的异种移植瘤。

磁场强度/序列:1.0 特斯拉/T 和 T 加权自旋回波。

评估

图像强度和对比测量。

统计检验

学生 t 检验。

结果

肿瘤内 SPION 扩散系数 D = 44.8 ± 2.4 × 10 mm /s。PSMA 阳性 LNCaP 和 C4-2 肿瘤摄取的铁与静脉内注射剂量从 60 nmol 到 1.6 μmol 成正比;注射 1 μmol 的抗 PSMA 偶联 SPION 导致肿瘤 [Fe] 为 76 μM。即使在最高铁剂量 1.6 μmol 时,PSMA 阴性 DU145 肿瘤也不会从抗 PSMA 偶联 SPION 中摄取显著的铁。当从注射的 SPION 制剂中省略针对 PSMA 的抗体时,观察到类似的非特异性摄取缺失。PSMA 阳性肿瘤摄取的初始铁剂量的分数为 2.32 ± 0.75%(n = 10);PSMA 阴性 DU145 肿瘤和没有抗 PSMA 抗体的 SPION 的摄取为 0.16 ± 0.34%(n = 7),这使得 PSMA + 肿瘤中的 [Fe] 与 PSMA-肿瘤中的 [Fe] 比值大于 15:1(P = 0.01)。

数据结论

抗 PSMA 偶联 SPION 的定量 [Fe]MRI 可区分体内 PSMA 阳性 LNCaP 和 C4-2 与 PSMA 阴性 DU145 人前列腺肿瘤异种移植瘤。

证据水平

1 技术功效:第 2 阶段 J. Magn. Reson. Imaging 2017. J. MAGN. RESON. IMAGING 2018;48:469-481.

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