School of Chemistry, University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Curr Top Med Chem. 2011;11(5):500-20. doi: 10.2174/156802611794785172.
Peptide targeted ⁶⁴Cu-labelled diagnostic agents for positron emission tomography are viable candidates for molecular imaging of cancer. In a clinical setting, optimal image quality relies on selective tumor uptake of the ⁶⁴Cu-labelled radiotracer. The three components of the radiotracer construct--the chelate group, linker and targeting peptide--all influence the biodistribution of the ⁶⁴Cu-labelled radiotracer in vivo. Low or moderate Cu complex stability in vivo results in transmetallation of ⁶⁴Cu to endogenous proteins, giving rise to high background activity. The length and the nature of the linker group affect the affinity of the ⁶⁴Cu-labelled radiotracer for the target receptor. Variations in the peptide sequence can impact on the metabolic stability and therefore the bioavailability and tumor retention of the ⁶⁴Cu-labelled radiotracer in vivo. Lastly, the hydrophilicity of the construct can influence radiotracer metabolism and clearance pathways. Recent advances in the field of peptide targeted ⁶⁴Cu-labelled radiopharmaceuticals involve GRPR-targeted and αvβ3 integrin receptor-targeted constructs. These constructs are based on the bombesin peptide sequence and the RGD recognition motif respectively. These examples are reviewed as case studies in the optimisation of ⁶⁴Cu radiotracer design.
肽靶向 ⁶⁴Cu 标记的诊断剂是正电子发射断层扫描（PET）分子成像的候选物。在临床环境中，最佳的图像质量依赖于肿瘤对 ⁶⁴Cu 标记放射性示踪剂的选择性摄取。放射性示踪剂构建的三个组成部分——螯合剂、连接子和靶向肽——都影响 ⁶⁴Cu 标记放射性示踪剂在体内的生物分布。体内低或中等 Cu 配合物稳定性导致 ⁶⁴Cu 向内源性蛋白的转金属化，从而导致高背景活性。连接子基团的长度和性质影响 ⁶⁴Cu 标记放射性示踪剂与靶受体的亲和力。肽序列的变化会影响放射性示踪剂的代谢稳定性，从而影响 ⁶⁴Cu 标记放射性示踪剂在体内的生物利用度和肿瘤滞留。最后，构建体的亲水性会影响放射性示踪剂的代谢和清除途径。肽靶向 ⁶⁴Cu 标记放射性药物领域的最新进展涉及 GRPR 靶向和 αvβ3 整合素受体靶向构建体。这些构建体分别基于蛙皮素肽序列和 RGD 识别基序。这些例子被作为 ⁶⁴Cu 放射性示踪剂设计优化的案例研究进行了综述。
