Frings Virginie, Yaqub Maqsood, Hoyng Lieke L, Golla Sandeep S V, Windhorst Albert D, Schuit Robert C, Lammertsma Adriaan A, Hoekstra Otto S, Smit Egbert F, Boellaard Ronald
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
J Nucl Med. 2014 Sep;55(9):1417-23. doi: 10.2967/jnumed.114.140913. Epub 2014 Jun 26.
3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET/CT provides a noninvasive assessment of proliferation and, as such, could be a valuable imaging biomarker in oncology. The aim of the present study was to assess the validity of simplified quantitative parameters of (18)F-FLT uptake in non-small cell lung cancer (NSCLC) patients before and after the start of treatment with a tyrosine kinase inhibitor (TKI).
Ten patients with metastatic NSCLC harboring an activating epidermal growth factor receptor mutation were included in this prospective observational study. Patients underwent (15)O-H2O and (18)F-FLT PET/CT scanning on 3 separate occasions: within 7 d before treatment, and 7 and 28 d after the first therapeutic dose of a TKI (gefitinib or erlotinib). Dynamic scans were acquired and venous blood samples were collected during the (18)F-FLT scan to measure parent fraction and plasma and whole-blood radioactivity concentrations. Simplified measures (standardized uptake value [SUV] and tumor-to-blood ratio [TBR]) were correlated with fully quantitative measures derived from kinetic modeling.
Twenty-nine of thirty (18)F-FLT PET/CT scans were evaluable. According to the Akaike criterion, a reversible 2-tissue model with 4 rate constants and blood volume parameter was preferred in 84% of cases. Relative therapy-induced changes in SUV and TBR correlated with those derived from kinetic analyses (r(2) = 0.83-0.97, P < 0.001, slope = 0.72-1.12). (18)F-FLT uptake significantly decreased at 7 and 28 d after the start of treatment compared with baseline (P < 0.01). Changes in (18)F-FLT uptake were not correlated with changes in perfusion, as measured using (15)O-H2O.
SUV and TBR could both be used as surrogate simplified measures to assess changes in (18)F-FLT uptake in NSCLC patients treated with a TKI, at the cost of a small underestimation in uptake changes or the need for a blood sample and metabolite measurement, respectively.
3'-脱氧-3'-(18)F-氟胸苷((18)F-FLT)PET/CT可对增殖进行无创评估，因此在肿瘤学中可能是一种有价值的成像生物标志物。本研究的目的是评估非小细胞肺癌(NSCLC)患者在开始使用酪氨酸激酶抑制剂(TKI)治疗前后(18)F-FLT摄取简化定量参数的有效性。
本前瞻性观察研究纳入了10例携带激活型表皮生长因子受体突变的转移性NSCLC患者。患者在3个不同时间点接受(15)O-H2O和(18)F-FLT PET/CT扫描：治疗前7天内，以及首次给予TKI(吉非替尼或厄洛替尼)治疗剂量后7天和28天。在(18)F-FLT扫描期间进行动态扫描并采集静脉血样，以测量母体分数以及血浆和全血放射性浓度。简化测量指标(标准化摄取值[SUV]和肿瘤与血液比值[TBR])与动力学建模得出的完全定量测量指标相关。
30次(18)F-FLT PET/CT扫描中有29次可评估。根据赤池准则，在84%的病例中，具有4个速率常数和血容量参数的可逆双组织模型更为合适。SUV和TBR相对治疗引起的变化与动力学分析得出的变化相关(r(2)=0.83-0.97，P<0.001，斜率=0.72-1.12)。与基线相比，治疗开始后7天和28天(18)F-FLT摄取显著降低(P<0.01)。使用(15)O-H2O测量的灌注变化与(18)F-FLT摄取变化不相关。
SUV和TBR均可作为替代简化测量指标，用于评估接受TKI治疗的NSCLC患者(18)F-FLT摄取的变化，代价分别是摄取变化略有低估或需要采集血样并测量代谢物。
