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全身照射后增殖和凋亡：在小鼠模型中的纵向 PET 研究。

Proliferation and apoptosis after whole-body irradiation: longitudinal PET study in a mouse model.

机构信息

Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany.

Comparative Experimental Pathology, Institute of Pathology, TU Munich, Munich, Germany.

出版信息

Eur J Nucl Med Mol Imaging. 2024 Jan;51(2):395-404. doi: 10.1007/s00259-023-06430-x. Epub 2023 Oct 5.

DOI:10.1007/s00259-023-06430-x
PMID:37796306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10774227/
Abstract

PURPOSE

A reliable method for regional in vivo imaging of radiation-induced cellular damage would be of great importance for the detection of therapy-induced injury to healthy tissue and the choice of adequate treatment of radiation emergency patients in both civilian and military events. This study aimed to investigate in a mouse model if positron emission tomography (PET) imaging with proliferation and apoptosis markers is potentially suitable for this purpose.

METHODS

Four groups, including twenty mice (wild-type C57BL/6) each, were whole-body irradiated with 0 Gy, 0.5 Gy, 1 Gy, and 3 Gy and examined by PET over a six-month period at defined time points. 3'-[F]fluoro-3'-deoxythymidine ([F]FLT) and 2-(5-[F]fluoropentyl)-2-methyl malonic acid ([F]ML-10) were used to visualise proliferation and apoptosis. Regional standard uptake values were compared with respect to irradiation dose over time. Histologic data and peripheral blood cell values were correlated with the PET results.

RESULTS

The hematopoietic bone marrow showed a significantly increased [F]FLT signal at early time points after radiation exposure (day 3 and day 7). This correlated with blood parameters, especially leukocytes, and histological data. A significantly increased [F]FLT signal also occurred in the gastrointestinal tract and thymus at early time points. An increased [F]ML-10 signal related to irradiation doses was observed in the bone marrow on day 8, but there was a high variability of standard uptake values and no correlation with histological data.

CONCLUSION

[F]FLT showed potential to visualise the extent, regional distribution and recovery from radiation-induced cellular damage in the bone marrow, gastrointestinal tract and thymus. The potential of [F]FLT imaging to assess the extent of bone marrow affected by irradiation might be especially useful to predict the subsequent severity of hematopoietic impairment and to adapt the therapy of the bone marrow reserve. [F]ML-10 PET proved to be not sensitive enough for the reliable detection of radiation induced apoptosis.

摘要

目的

对于检测治疗引起的健康组织损伤以及选择适当的辐射急症患者治疗方法，在体内对辐射诱导的细胞损伤进行区域成像的可靠方法非常重要。本研究旨在通过在小鼠模型中研究增殖和凋亡标志物的正电子发射断层扫描（PET）成像是否适合此目的。

方法

对包括二十只（野生型 C57BL/6）小鼠在内的四组小鼠进行全身照射，照射剂量分别为 0Gy、0.5Gy、1Gy 和 3Gy，并在六个月的时间内通过 PET 在定义的时间点进行检查。3'-[F]氟-3'-脱氧胸苷([F]FLT)和 2-(5-[F]氟戊基)-2-甲基丙二酸([F]ML-10)用于观察增殖和凋亡。将区域标准摄取值与随时间的照射剂量进行比较。将组织学数据和外周血细胞值与 PET 结果相关联。

结果

造血骨髓在辐射暴露后的早期时间点（第 3 天和第 7 天）显示出明显增加的[F]FLT 信号。这与血液参数尤其是白细胞以及组织学数据相关。在早期时间点，胃肠道和胸腺中也观察到明显增加的[F]FLT 信号。在第 8 天，骨髓中观察到与照射剂量相关的增加的[F]ML-10 信号，但标准摄取值的变异性很大，与组织学数据没有相关性。

结论

[F]FLT 具有可视化骨髓、胃肠道和胸腺中辐射诱导的细胞损伤的范围、区域分布和恢复的潜力。[F]FLT 成像评估受照射骨髓范围的潜力可能特别有助于预测随后造血功能障碍的严重程度，并调整骨髓储备的治疗方法。[F]ML-10 PET 证明对于可靠检测辐射诱导的细胞凋亡不够敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/417d6483d8e1/259_2023_6430_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/919361078d42/259_2023_6430_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/c0ce12e259d3/259_2023_6430_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/2c3bf1fd389e/259_2023_6430_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/f3946acd6eaa/259_2023_6430_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/87ce46615f07/259_2023_6430_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/5e76923eb13c/259_2023_6430_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/b084a9a8d267/259_2023_6430_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/417d6483d8e1/259_2023_6430_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/919361078d42/259_2023_6430_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/c0ce12e259d3/259_2023_6430_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/2c3bf1fd389e/259_2023_6430_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/f3946acd6eaa/259_2023_6430_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/87ce46615f07/259_2023_6430_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/5e76923eb13c/259_2023_6430_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/b084a9a8d267/259_2023_6430_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa3/10774227/417d6483d8e1/259_2023_6430_Fig8_HTML.jpg

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