Tehrani Omid S, Muzik Otto, Heilbrun Lance K, Douglas Kirk A, Lawhorn-Crews Jawana M, Sun Haihao, Mangner Thomas J, Shields Anthony F
Karmanos Cancer Institute, Wayne State University, 4100 John R. Street, Detroit, MI 48201, USA.
J Nucl Med. 2007 Sep;48(9):1436-41. doi: 10.2967/jnumed.107.042762.
The kinetics of 1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)thymine (FMAU) were studied using PET to determine the most appropriate and simplest approach to image acquisition and analysis. The concept of tumor retention ratio (TRR) is introduced and validated.
Ten patients with brain (n = 4) or prostate (n = 6) tumors were imaged using (18)F-FMAU PET (mean dose, 369 MBq). Sixty-minute dynamic images were obtained; this was followed by whole-body images. Mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) of each tumor were determined as the mean over 3 planes of each time interval. For kinetic analyses, blood activity was measured in 18 samples over 60 min. Samples were analyzed by high-performance liquid chromatography at 3 selected times to determine tracer metabolites. FMAU kinetics were measured using a 3-compartment model yielding the flux (K1 x k3/(k2 + k3)) (K1, k2, and k3 are rate constants) and compared with TRR measurements. TRR was calculated as the tumor (18)F-FMAU uptake area under the curve divided by the product of blood (18)F-FMAU AUC and time. A similar analysis was performed using muscle to estimate (18)F-FMAU delivery.
SUVmean measurements obtained from 5 to 11 min correlated with those obtained from 30 to 60 min (r(2) = 0.92, P < 0.0001) and 50 to 60 min (r(2) = 0.92, P < 0.0001) due to the rapid clearance of (18)F-FMAU. Similar results were obtained using SUVmax measurements (r(2) = 0.93, P < 0.0001; r(2) = 0.88, P < 0.0001, respectively). The measurement of TRR using either blood or muscle activity over 11 min provided results comparable to those of 60-min dynamic imaging and a 3-compartment model. This analysis required only 5 blood samples drawn at 1, 2, 3, 5, and 11 min without metabolite correction to produce comparable results.
Tissue retention ratio measurements obtained over 11 min can replace flux measurements in (18)F-FMAU imaging. The SUVmean and the SUVmax in 5-11 min images correlated well with those of images obtained at 50-60 min. The quality of the images and tissue kinetics in 11 min of imaging makes it a desirable and shorter tumor imaging option.
使用正电子发射断层扫描(PET)研究了1-(2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基)胸腺嘧啶(FMAU)的动力学,以确定图像采集和分析最合适、最简单的方法。引入并验证了肿瘤滞留率(TRR)的概念。
10例脑肿瘤(n = 4)或前列腺肿瘤(n = 6)患者接受了(18)F-FMAU PET成像(平均剂量,369 MBq)。获得了60分钟的动态图像;随后进行全身图像采集。确定每个肿瘤的平均和最大标准化摄取值(分别为SUVmean和SUVmax),作为每个时间间隔3个平面的平均值。对于动力学分析,在60分钟内采集18个样本测量血液活性。在3个选定时间通过高效液相色谱分析样本以确定示踪剂代谢物。使用三室模型测量FMAU动力学,得出通量(K1×k3/(k2 + k3))(K1、k2和k3为速率常数),并与TRR测量结果进行比较。TRR计算为肿瘤(18)F-FMAU曲线下摄取面积除以血液(18)F-FMAU曲线下面积(AUC)与时间的乘积。使用肌肉进行类似分析以估计(18)F-FMAU的输送。
由于(18)F-FMAU的快速清除,5至11分钟获得的SUVmean测量值与30至60分钟(r(2) = 0.92,P < 0.0001)和50至60分钟(r(2) = 0.92,P < 0.0001)获得的测量值相关。使用SUVmax测量也得到了类似结果(分别为r(2) = 0.93,P < 0.0001;r(2) = 0.88,P < 0.0001)。在11分钟内使用血液或肌肉活性测量TRR,其结果与60分钟动态成像和三室模型的结果相当。该分析仅需要在第1、2、3、5和11分钟采集5份血样,无需进行代谢物校正即可产生可比结果。
在(18)F-FMAU成像中,11分钟内获得的组织滞留率测量值可替代通量测量。5至11分钟图像中的SUVmean和SUVmax与50至60分钟获得的图像中的值相关性良好。11分钟成像的图像质量和组织动力学使其成为理想且更短的肿瘤成像选择。