Synthesis and Preclinical Evaluation of DDR1-Targeted Radiotracers for Colorectal Cancer Diagnosis

Colorectal cancer (CRC) is one of the most common tumors, and discoidin domain receptor 1 (DDR1) expression is significantly higher in CRC. In this study, we designed and synthesized eight novel ⁶⁸Ga-labeled DDR1-targeted radiotracers. The radiochemical purities (RCPs) of radiotracers were all over 95%; except for [⁶⁸Ga]Ga-MYZ02 and [⁶⁸Ga]Ga-MYZ06, other six radiotracers showed high stability <i>in vitro</i> and <i>in vivo</i>. The equilibrium dissociation constants (<i>K</i>_D) of radiotracers were all in the nanomolar range. Micro-PET/CT imaging and biodistribution study showed that [⁶⁸Ga]Ga-MYZ04, which exhibits favorable pharmacokinetic properties, could clearly visualize tumors at 1 h postinjection. Among the six radiotracers, [⁶⁸Ga]Ga-MYZ04 had the highest tumor-to-muscle ratio (T/M: 4.21 ± 0.51), a higher tumor-to-liver ratio (T/L: 0.71 ± 0.06), and the lowest tumor-to-kidney ratio (<i>T</i>/K: 0.55 ± 0.03), suggesting a superior metabolic pathway with primary clearance through the urinary system. This makes it promising for the imaging diagnosis of DDR1-positive expressing CRC.