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 in vitro and in vivo. The equilibrium dissociation constants (KD) 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 (T/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.