Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mol Pharm. 2011 Jun 6;8(3):736-47. doi: 10.1021/mp100358f. Epub 2011 Apr 6.
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, ¹²⁴I has the longest physical half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes ¹²⁴I very attractive for pharmacological studies. However, the high energy of the positrons emitted by ¹²⁴I and the presence of single photons in the ¹²⁴I emission can potentially introduce limitations in the quantitative analysis of the images. The objective of this research was to determine whether the use of ¹²⁴I 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 ¹²⁴I, 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 ¹²⁴I is an excellent label for quantitative pharmacological PET imaging studies.
随着越来越多的生物技术产品和药物输送系统进入临床前和临床研究，正电子发射断层扫描（PET）药理学成像研究发挥着越来越重要的作用。此类研究通常需要研究缓慢而复杂的药代动力学（PK）。这表明候选药物需要用具有长物理半衰期的放射性核素进行标记。在目前可用的 PET 正电子发射体中，¹²⁴I 的物理半衰期最长（4.2 天）。这一点，加上碘在体内的良好研究行为，使得¹²⁴I 非常适合用于药理学研究。然而，¹²⁴I 发射的正电子的高能量以及¹²⁴I 发射中的单光子的存在，可能会对图像的定量分析引入限制。本研究的目的是确定¹²⁴I 作为 PET 标记物是否能提供适合 PK 研究的数据质量。该研究使用 MicroPET P4 扫描仪（西门子/协和微系统公司）进行。使用线源和圆柱形体模测量空间分辨率、计数率性能、灵敏度和散射分数。使用人体重组蛋白在大鼠和食蟹猴中进行模型动物研究。这些蛋白质用¹²⁴I 标记，最高可达 185MBq/mg。在相机的中心，OSEM3D/MAP 的横向和轴向空间分辨率比 FORE-2DFBP 更高（FWHM 分别为 2.52 毫米和 3.31 毫米，3.10 毫米和 3.69 毫米）。真符合计数率的线性度在高达 44MBq 时观察到。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，对于啮齿动物为每只动物 2-10MBq，对于较大的动物为每公斤体重 4-10MBq，在从分钟（动态研究）到 10 天的所有实验时间范围内，数值数据的质量都适合 PK 分析。总的来说，这些数据表明，¹²⁴I 是定量药理学 PET 成像研究的极佳标记物。
