Iodine-124 as a Label for Pharmacological PET Imaging
Iodine-124 as a Label for Pharmacological PET Imaging
复制标题
DOI：
10.1021/mp100358f
复制
发表时间：
2011-05-01
影响因子：
4.9
通讯作者：
Papisov, Mikhail I.
中科院分区：
文献类型：
--
作者：
Belov, Vasily V.;Bonab, Ali A.;Papisov, Mikhail I.
随着越来越多的生物技术产品和药物释放系统进入临床前和临床研究，PET的药物成像研究发挥着越来越重要的作用。这类研究通常需要研究缓慢而复杂的药代动力学(PK)。这表明用具有较长物理半衰期的放射性核素标记候选药物。在目前可用的正电子发射体中，(124)1具有最长的物理半衰期(4.2天)。这一点，再加上碘在体内的良好行为，使I-124对药理学研究非常有吸引力。然而，I-124发射的正电子的高能量以及I-124发射的单个光子的存在可能会给图像的定量分析带来限制。这项研究的目的是确定使用I-124作为PET标签是否提供了适合PK研究的数据质量。这项研究使用MicroPET P4扫描仪(西门子/协和微系统)进行。使用线源和柱状体模测量了空间分辨率、计数率性能、灵敏度和散射分数。用重组人蛋白在大鼠和食蟹猴身上进行了动物模型研究。I-124标记的蛋白质最高可达185MBq/mg。OSEM3D/MAP的轴向和轴向分辨率均令人满意，且高于前2DFBP(FWHM 2.52比3.31 mm，3.10比3.69 mm)。真符合计数率的线性度高达44mBq。动物研究表明，即使是非常小的器官也能很好地描绘和分辨。在最佳剂量下，啮齿类动物每只动物2-10MBq，大型动物每公斤体重4-10MBq，在从几分钟(动态研究)到10天的所有实验时间范围内，数字数据的质量都适合PK分析。总体而言，数据表明I-124是定量药理学PET成像研究的极佳标记物。
With the growing number of biotechnology products and drug delivery systems entering preclinical and clinical studies, pharmacological imaging studies with PET play an increasingly significant role. Such studies often require investigation of slow and complex pharmacokinetics (PK). This suggests labeling of the drug candidate with radionuclides that have long physical half-lives. Among the currently available PET positron emitters, (124)1 has the longest physical half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes I-124 very attractive for pharmacological studies. However, the high energy of the positrons emitted by I-124 and the presence of single photons in the I-124 emission can potentially introduce limitations in the quantitative analysis of the images. The objective of this research was to determine whether the use of I-124 as a PET label provides data quality suitable for PK studies. The study was carried out using MicroPET P4 scanner (Siemens/Concorde Microsystems). Spatial resolution, count-rate performance, sensitivity and scatter fraction were measured using a line source and a cylindrical phantom. Model animal studies in rats and cynomolgus monkeys were carried out using human recombinant proteins. The proteins were labeled with I-124, up to 185 MBq/mg. The transaxial and axial spatial resolutions in the center of the camera were satisfactory and higher for OSEM3D/MAP than FORE-2DFBP (FWHM 2.52 vs 3.31 mm, and 3.10 vs 3.69 mm). Linearity of the true coincidence count-rate was observed up to 44 MBq. Animal studies demonstrated excellent delineation and resolution of even very small organs. At optimal doses, 2-10 MBq per animal for rodents and 4-10 MBq per kg of body weight for larger animals, the quality of numerical data was appropriate for PK analysis in all experimental timeframes from minutes (dynamic studies) to 10 days. Overall, the data suggest that I-124 is an excellent label for quantitative pharmacological PET imaging studies.