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使用氘代水诱导的 2H-组织标记的氘磁共振成像可在临床场强下监测癌症治疗。

Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength.

机构信息

Department of Radiology, Gifu University, Gifu, Japan.

Department of Radiological Technology, Central Japan International Medical Center, Gifu, Japan.

出版信息

Clin Cancer Res. 2023 Dec 15;29(24):5173-5182. doi: 10.1158/1078-0432.CCR-23-1635.

Abstract

PURPOSE

An accurate and noninvasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice.

EXPERIMENTAL DESIGN

MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2-bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS, and histopathology were performed.

RESULTS

The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI, and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments.

CONCLUSIONS

Deuterium MRI at 1.5T proved feasible to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.

摘要

目的

除了传统的解剖成像技术外,准确且无创的肿瘤治疗后反应评估至关重要。高场磁共振成像(MRI)使用氘标记分子已被证明是癌症代谢成像的替代方法。本研究旨在使用 2H 组织标记和临床场强下的氘 MRI 对胰腺癌模型小鼠中的三种抗癌疗法进行肿瘤可视化和评估。

实验设计

制备 BALB/c-nu 小鼠的 MIA PaCa-2 胰腺癌细胞和 C26 结直肠癌细胞模型,并在自由饮用 30% D2O 的前 10 天内重复进行氘 MRI,以跟踪组织中 2H 的分布。还测量了 MIA PaCa-2 荷瘤小鼠照射、贝伐单抗给药或吉西他滨给药后肿瘤内 2H 的积累。进行了确证性质子 MRI、体外代谢极化 13C-MRS 和组织病理学检查。

结果

小鼠全身的 2H 分布在饮用后 1 天即可见,信号强度每天增加。虽然照射后 1 天和 3 天肿瘤大小没有变化,但 2H 的量明显减少。贝伐单抗或吉西他滨给药后,肿瘤的 2H 图像强度也显著降低。代谢极化 13C-MRS、质子 MRI 和 2H-NMR 光谱证实了抗癌治疗的疗效。

结论

1.5T 下的氘 MRI 可在 D2O 给药期间证明对跟踪小鼠组织中的 2H 分布是可行的,并显示肿瘤异种移植物中 2H 的积累更高。这项研究证明了一种有前途的癌症放化疗初步评估的成功方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2514/10722130/936012ecc68d/5173fig1.jpg

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