Chemistry Department, 2036 Main Mall, University of British Columbia, Vancouver, B.C., Canada.
Nucl Med Biol. 2013 Aug;40(6):841-9. doi: 10.1016/j.nucmedbio.2013.05.002. Epub 2013 Jun 27.
Positron Emission Tomography (PET) is a rapidly expanding, cutting edge technology for preclinical evaluation, cancer diagnosis and staging, and patient management. A one-step aqueous (18)F-labeling method, which can be applied to peptides to provide functional in vivo images, has been a long-standing challenge in PET imaging. Over the past few years, we have sought a rapid and mild radiolabeling method based on the aqueous radiosynthesis of in vivo stable aryltrifluoroborate (ArBF(3)(-)) conjugates. Recent access to production levels of (18)F-Fluoride led to a fluorescent-(18)F-ArBF(3)(-) at unprecedentedly high specific activities of 15Ci/μmol. However, extending this method to labeling peptides as imaging agents has not been explored.
In order to extend these results to a peptide of clinical interest in the context of production-level radiosynthesis, we applied this new technology for labeling RGD, measured its specific activity by standard curve analysis, and carried out a preliminary evaluation of its imaging properties.
RGD was labeled in excellent radiochemical yields at exceptionally high specific activity (~14Ci/μmol) (n = 3). Preliminary tumor-specific images corroborated by ex vivo biodistribution data with blocking controls show statistically significant albeit relatively low tumor uptake along with reasonably high tumor:blood ratios (n = 3).
Isotope exchange on a clinically useful (18)F-ArBF(3)(-) radiotracer leads to excellent radiochemical yields and exceptionally high specific activities while the anionic nature of the aryltrifluoroborate prosthetic results in very rapid clearance. Since rapid clearance of the radioactive tracer is generally desirable for tracer development, these results suggest new directions for varying linker arm composition to slightly retard clearance rather than enhancing it.
This work is the first to use production levels of (18)F-activity to directly label RGD at specific activities that are an order of magnitude higher than most reports and thereby increases the distribution window for radiotracer production and delivery.
正电子发射断层扫描（PET）是一种快速发展的前沿技术，可用于临床前评估、癌症诊断和分期以及患者管理。一种一步法的水性（18）F 标记方法，可应用于肽以提供体内功能图像，一直是 PET 成像中的一个长期挑战。在过去的几年中，我们一直在寻找一种基于体内稳定的芳基三氟硼酸盐（ArBF(3)(-)）缀合物的水性放射合成的快速温和的放射性标记方法。最近获得的（18）F-氟化物生产水平导致了前所未有的高比活度 15Ci/μmol 的荧光-（18）F-ArBF(3)(-)。然而，将这种方法扩展到标记作为成像剂的肽尚未得到探索。
为了将这些结果扩展到生产水平放射合成背景下具有临床意义的肽，我们将这项新技术应用于 RGD 的标记，通过标准曲线分析测量其比活度，并对其成像特性进行初步评估。
RGD 以极好的放射化学产率和极高的比活度（~14Ci/μmol）（n=3）进行标记。用阻断对照进行的初步肿瘤特异性图像与体外生物分布数据一致，显示出统计学上显著但相对较低的肿瘤摄取，同时具有合理高的肿瘤：血液比（n=3）。
临床有用的（18）F-ArBF(3)(-)放射性示踪剂的同位素交换导致极好的放射化学产率和极高的比活度，而芳基三氟硼酸盐假体的阴离子性质导致非常快速的清除。由于放射性示踪剂的快速清除通常是示踪剂开发所期望的，因此这些结果表明可以改变连接臂组成以稍微延迟清除而不是增强清除的新方向。
这项工作是首次使用生产水平的（18）F-活性直接标记 RGD，其比活度比大多数报道高一个数量级，从而增加了放射性示踪剂生产和输送的分布窗口。
