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非小细胞肺癌患者[18F]FAZA 的药代动力学分析。

Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients.

机构信息

Department of Radiology & Nuclear Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands,

出版信息

Eur J Nucl Med Mol Imaging. 2013 Oct;40(10):1523-31. doi: 10.1007/s00259-013-2462-3. Epub 2013 Jun 6.

DOI:10.1007/s00259-013-2462-3
PMID:23740374
Abstract

PURPOSE

[(18)F]Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within a tumour. The aims of this study were to determine the optimal kinetic model along with validation of using alternatives to arterial blood sampling for analysing [(18)F]FAZA studies and to assess the validity of simplified analytical methods.

METHODS

Dynamic 70-min [(18)F]FAZA PET/CT scans were obtained from nine non-small cell lung cancer patients. Continuous arterial blood sampling, together with manual arterial and venous sampling, was performed to derive metabolite-corrected plasma input functions. Volumes of interest (VOIs) were defined for tumour, healthy lung muscle and adipose tissue generating [(18)F]FAZA time-activity curves (TACs). TACs were analysed using one- and two-tissue compartment models using both metabolite-corrected blood sampler plasma input functions (BSIF) and image-derived plasma input functions (IDIF).

RESULTS

The reversible two-tissue compartment model with blood volume parameter (2T4k+VB) best described kinetics of [(18)F]FAZA in tumours. Volumes of distribution (VT) obtained using IDIF correlated well with those derived using BSIF (R(2) = 0.82). Venous samples yielded the same radioactivity concentrations as arterial samples for times >50 min post-injection (p.i.). In addition, both plasma to whole blood ratios and parent fractions were essentially the same for venous and arterial samples. Both standardised uptake value (SUV), normalised to lean body mass, and tumour to blood ratio correlated well with VT (R(2) = 0.77 and R(2) = 0.87, respectively, at 50-60 min p.i.), although a bias was observed at low VT.

CONCLUSION

The 2T4k+VB model provided the best fit to the dynamic [(18)F]FAZA data. IDIF with venous blood samples can be used as input function. Further data are needed to validate the use of simplified methods.

摘要

目的

[(18)F]氟阿霉素阿拉伯糖苷(FAZA)是一种正电子发射断层扫描(PET)示踪剂,旨在识别肿瘤内的缺氧区域。本研究的目的是确定最佳动力学模型,以及验证替代动脉采血分析[(18)F]FAZA 研究的方法,并评估简化分析方法的有效性。

方法

对 9 名非小细胞肺癌患者进行了 70 分钟的动态[(18)F]FAZA PET/CT 扫描。连续进行动脉采血,以及手动动脉和静脉采血,以获得代谢校正的血浆输入函数。为肿瘤、健康肺肌肉和脂肪组织定义了感兴趣体积(VOI),生成[(18)F]FAZA 时间-活性曲线(TAC)。使用代谢校正的血液采样器血浆输入函数(BSIF)和图像衍生的血浆输入函数(IDIF),通过单组织和双组织室模型分析 TAC。

结果

在肿瘤中,具有血容量参数(2T4k+VB)的可逆双组织室模型能最好地描述[(18)F]FAZA 的动力学。使用 IDIF 获得的分布容积(VT)与使用 BSIF 获得的分布容积(VT)密切相关(R²=0.82)。静脉样本在注射后 50 分钟以上时间点获得的放射性浓度与动脉样本相同(p.i.)。此外,静脉和动脉样本的血浆与全血比值和母体分数基本相同。标准摄取值(SUV),归一化到瘦体重,以及肿瘤与血液的比值与 VT 密切相关(在 50-60 分钟 p.i.时,R²分别为 0.77 和 0.87),尽管在低 VT 时观察到偏差。

结论

2T4k+VB 模型为动态[(18)F]FAZA 数据提供了最佳拟合。可以使用静脉血样本的 IDIF 作为输入函数。需要进一步的数据来验证简化方法的使用。

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