Peptide-Based PET Imaging Differentiates Netrin-1 Expression in Tumors

Neuroaxonal guidance factor-1 (Netrin-1) is a secreted glycoprotein overexpressed in cancer. It promotes tumor growth and metastasis and has demonstrated potential as a biomarker for tumor theranostics. In this study, we developed a novel Ga-68 labeled peptide radiotracer, termed [⁶⁸Ga]Ga-DKP, to assess the expression of netrin-1 in tumors. The tracer exhibited high radiochemical purity (over 95%) and strong stability. In vitro cellular assays demonstrated that A549 and 4T1 cells exhibited stronger binding capabilities for the probe than those in A375 cells, as they expressed higher levels of netrin-1. Furthermore, a blocking assay in A549 cells confirmed the affinity and specificity of the probe for netrin-1. In vivo PET/CT imaging and biodistribution studies demonstrated rapid tumor uptake and tissue excretion. A549 and 4T1 tumor-bearing mice showed higher tumor-to-muscle ratios (9.70 ± 1.24 and 10.94 ± 3.44, respectively) at 2 h postinjection, which were approximately 3-fold higher than A375 tumors. In conclusion, [⁶⁸Ga]Ga-DKP could be used to quantify netrin-1 levels, showing potential for clinical application.