Abstract：
Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [18F]FNA-N-CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [18F]FNA-N-CooP was prepared by highly chemoselective N-acylation and characterized using different chemical approaches. We validated its binding to the target using in vitro tissue section autoradiography and performed stability tests in vitro and in vivo. [18F]FNA-N-CooP was successfully synthesized in 16.8% decay-corrected radiochemical yield with high radiochemical purity (98.5%). It exhibited heterogeneous binding on brain metastasis tissue sections from a patient with breast cancer, with foci of radioactivity binding corresponding to FABP3 positivity. Furthermore, the tracer binding was reduced by 55% in the presence of nonradioactive FNA-N-CooP a blocker, indicating specific tracer binding and that FABP3 is a viable target for [18F]FNA-N-CooP. Favorably, the tracer did not bind to necrotic tumor tissue. However, [18F]FNA-N-CooP displayed limited stability both in vitro in mouse plasma or human serum and in vivo in mouse, therefore further studies are needed to improve the stability [18F]FNA-N-CooP to be used for in vivo applications.
摘要：
脂肪酸结合蛋白3（FABP3）在肿瘤细胞和肿瘤血管中都有表达，使其成为医学成像和治疗的潜在目标。在这项研究中,我们的目的是用游离氨基和巯基放射性标记CooP肽，并通过正电子发射断层扫描评估放射性标记产物[18F]FNA-N-CooP对乳腺癌脑转移瘤中FABP3表达的成像。[18F]FNA-N-CooP通过高度化学选择性N-酰化制备并使用不同的化学方法表征。我们使用体外组织切片放射自显影术验证了其与靶标的结合，并在体外和体内进行了稳定性测试。[18F]FNA-N-CooP以16.8%的衰变校正放射化学产率和高放射化学纯度(98.5%)成功合成。它在乳腺癌患者的脑转移组织切片上表现出异质结合，具有对应于FABP3阳性的放射性结合灶。此外，在存在非放射性FNA-N-CooP阻断剂的情况下，示踪剂结合减少了55％，表明特异性示踪剂结合和FABP3是[18F]FNA-N-CooP的可行靶标。有利的是,示踪剂未与坏死肿瘤组织结合。然而,[18F]FNA-N-CooP在小鼠血浆或人血清中的体外和小鼠体内显示出有限的稳定性，因此需要进一步的研究来提高[18F]FNA-N-CooP的稳定性以用于体内应用。
