Optimisation of Animal Handing and Timing of 2-deoxy-2-[¹⁸F]fluoro-D-glucose PET Tumour Imaging in Mice.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Molecular Imaging and Biology Pub Date : 2024-12-01 Epub Date: 2024-11-11 DOI:10.1007/s11307-024-01956-4

Richard L Hesketh, David Y Lewis, Kevin M Brindle

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Abstract

Purpose: In humans, 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60 min. Similar studies have not been performed in mice and the static imaging time point for most studies is arbitrarily set at 30 - 60 min post-injection of [¹⁸F]FDG. Ideally, static PET imaging should be performed after the initial period of rapid uptake but this period has not been defined in mice, with previous dynamic studies in mice being limited to 60 min. This study aimed to define the kinetics of [¹⁸F]FDG biodistribution over periods of 3 - 4 h in different murine tumour models, both subcutaneous and autochthonous, and to further refine fasting and warming protocols used prior to imaging.

Procedures: Dynamic [¹⁸F]FDG PET-CT scans lasting 3 or 4 h were performed with C57BL/6 J and Balb/c nude mice bearing subcutaneous EL4 murine T-cell lymphoma and Colo205 human colorectal tumours, respectively, and with transgenic Eμ-Myc lymphoma mice. Prior to [¹⁸F]FDG injection, four combinations of different animal handling conditions were used: warming for 1 h at 31 °C; maintenance at room temperature (20 - 24 °C), fasting for 6 - 10 h and a fed state.

Results: Tumour mean standardised uptake value (SUV_mean) peaked at 147 ± 48 min post injection in subcutaneous tumours and 74 ± 31 min in autochthonous Eμ-Myc lymphomas. The tumour-to-blood ratio (TBR) peaked at 171 ± 57 and 83 ± 33 min in subcutaneous and autochthonous Eμ-Myc tumours, respectively. Fasting increased tumour [¹⁸F]FDG uptake and suppressed myocardial uptake in EL4 tumour-bearing mice. There was a good correlation between tumour SUV_mean and K_i calculated using an input function (IDIF) derived from the inferior vena cava.

Conclusions: Delayed static [¹⁸F]FDG-PET imaging (> 60 min) in both autochthonous and subcutaneous tumours in improved tumour-to-background contrast and increased reproducibility.

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优化小鼠 2-脱氧-2-[18F]氟-D-葡萄糖 PET 肿瘤成像的动物处理和时间安排。

目的：在人体中，2-脱氧-2-[18F]氟-D-葡萄糖（[18F]FDG）的肿瘤与背景对比度在典型的摄取期（45-60 分钟）后仍会持续上升。在小鼠中还没有进行过类似的研究，大多数研究的静态成像时间点被随意设定为注射[18F]FDG 后的 30 - 60 分钟。理想情况下，静态 PET 成像应在快速吸收的初始阶段后进行，但小鼠的这一阶段尚未确定，之前的小鼠动态研究仅限于 60 分钟。本研究旨在确定[18F]FDG在不同小鼠皮下和自身肿瘤模型中3-4小时的生物分布动力学，并进一步完善成像前的禁食和保温方案：对分别患有皮下 EL4 小鼠 T 细胞淋巴瘤和 Colo205 人类结直肠肿瘤的 C57BL/6 J 和 Balb/c 裸鼠以及转基因 Eμ-Myc 淋巴瘤小鼠进行了持续 3 或 4 小时的动态 [18F]FDG PET-CT 扫描。在注射[18F]FDG之前，使用了四种不同的动物处理条件组合：31 °C下保温1小时；室温（20 - 24 °C）下维持；禁食6 - 10小时和进食状态：皮下肿瘤的平均标准化摄取值（SUVmean）在注射后 147 ± 48 分钟达到峰值，自体 Eμ-Myc 淋巴瘤的平均标准化摄取值（SUVmean）在注射后 74 ± 31 分钟达到峰值。皮下肿瘤和自体Eμ-Myc淋巴瘤的瘤血比（TBR）分别在注射后171±57分钟和83±33分钟达到峰值。空腹可增加EL4肿瘤小鼠的肿瘤[18F]FDG摄取量，抑制心肌摄取量。肿瘤SUVmean与使用下腔静脉输入函数（IDIF）计算的Ki之间存在良好的相关性：结论：对自体和皮下肿瘤进行延迟静态[18F]FDG-PET成像（> 60 分钟）可改善肿瘤与背景的对比度并提高再现性。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.