使用正电子发射断层显像/计算机断层扫描（PET/CT）对非小细胞肺癌（NSCLC）患者的[F]阿法替尼进行定量分析：一项可行性研究。
Quantification of [F]afatinib using PET/CT in NSCLC patients: a feasibility study.
作者信息
van de Stadt E A, Yaqub M, Lammertsma A A, Poot A J, Schober P R, Schuit R C, Smit E F, Bahce I, Hendrikse N H
机构信息
Department of Pulmonology, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
出版信息
EJNMMI Res. 2020 Aug 17;10(1):97. doi: 10.1186/s13550-020-00684-4.
INTRODUCTION
Only a subgroup of non-small cell lung cancer (NSCLC) patients benefit from treatment using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as afatinib. Tumour uptake of [F]afatinib using positron emission tomography (PET) may identify those patients that respond to afatinib therapy. Therefore, the aim of this study was to find the optimal tracer kinetic model for quantification of [F]afatinib uptake in NSCLC tumours.
METHODS
[F]Afatinib PET scans were performed in 10 NSCLC patients. The first patient was scanned for the purpose of dosimetry. Subsequent patients underwent a 20-min dynamic [O]HO PET scan (370 MBq) followed by a dynamic [F]afatinib PET scan (342 ± 24 MBq) of 60 or 90 min. Using the Akaike information criterion (AIC), three pharmacokinetic plasma input models were evaluated with both metabolite-corrected sampler-based input and image-derived (IDIF) input functions in combination with discrete blood samples. Correlation analysis of arterial on-line sampling versus IDIF was performed. In addition, perfusion dependency and simplified measures were assessed.
RESULTS
Ten patients were included. The injected activity of [F]afatinib was 341 ± 37 MBq. Fifteen tumours could be identified in the field of view of the scanner. Based on AIC, tumour kinetics were best described using an irreversible two-tissue compartment model and a metabolite-corrected sampler-based input function (Akaike 50%). Correlation of plasma-based input functions with metabolite-corrected IDIF was very strong (r = 0.93). The preferred simplified uptake parameter was the tumour-to-blood ratio over the 60- to 90-min time interval (TBR). Tumour uptake of [F]afatinib was independent of perfusion.
CONCLUSION
The preferred pharmacokinetic model for quantifying [F]afatinib uptake in NSCLC tumours was the 2T3K_vb model. TBR showed excellent correlation with this model and is the best candidate simplified method.
TRIAL REGISTRATION
https://eudract.ema.europa.eu/ nr 2012-002849-38.
引言
只有一小部分非小细胞肺癌（NSCLC）患者能从使用表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）如阿法替尼的治疗中获益。利用正电子发射断层扫描（PET）测定[F]阿法替尼在肿瘤中的摄取情况，可能有助于识别那些对阿法替尼治疗有反应的患者。因此，本研究的目的是寻找用于定量NSCLC肿瘤中[F]阿法替尼摄取的最佳示踪剂动力学模型。
方法
对10例NSCLC患者进行了[F]阿法替尼PET扫描。第一位患者扫描是为了进行剂量测定。随后的患者先进行了20分钟的动态[O]HO PET扫描（370MBq），然后进行了60或90分钟的动态[F]阿法替尼PET扫描（342±24MBq）。使用赤池信息准则（AIC），结合代谢物校正的基于采样器的输入函数和图像衍生（IDIF）输入函数以及离散血样，评估了三种药代动力学血浆输入模型。对动脉在线采样与IDIF进行了相关性分析。此外，还评估了灌注依赖性和简化测量方法。
结果
纳入了10例患者。[F]阿法替尼的注射活度为341±37MBq。在扫描仪视野内可识别出15个肿瘤。基于AIC，使用不可逆双组织室模型和代谢物校正的基于采样器的输入函数（赤池50%）能最好地描述肿瘤动力学。基于血浆的输入函数与代谢物校正的IDIF的相关性非常强（r = 0.93）。首选的简化摄取参数是60至90分钟时间间隔内的肿瘤与血液比值（TBR）。[F]阿法替尼在肿瘤中的摄取与灌注无关。
结论
用于定量NSCLC肿瘤中[F]阿法替尼摄取的首选药代动力学模型是2T3K_vb模型。TBR与该模型显示出极好的相关性，是最佳的简化方法候选者。
试验注册
https://eudract.ema.europa.eu/ nr 2012-002849-38。
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