Developments of Quinoline-Engineered Radioligands for Melanin-Targeted PET Imaging
Jiale Zhang, Hao Wang, Xinying Zeng, Xingxing Cheng, Jiahui Sun, Yanjie Wang, Zhexin He, Wuhao Zhou, Rongqiang Zhuang, Hongwu Liu, Zhide Guo, Heqing YiAbstract
A quinoline-based platform was developed to generate melanin-targeted radiotracers suitable for 68Ga-labeling. Four quinoline derivatives integrating a melanin-binding moiety and a radiometal chelator were synthesized and evaluated. All tracers exhibited high hydrophilicity (Log P −2.86 to −2.50) and good radiochemical stability. Among them, [68Ga]Ga-D-6-2-DMA showed the most favorable in vivo performance, with high tumor uptake in B16F10 melanoma (3.00 ± 0.25% ID/g at 0.5 h; 2.75 ± 0.25% ID/g at 2 h) and results consistent with biodistribution. Blocking studies confirmed melanin-specific targeting, and negligible uptake was observed in non-melanoma A375 xenografts. In melanoma lung metastasis models, [68Ga]Ga-D-6-2-DMA clearly visualized metastatic lesions, which correlated with bioluminescence imaging and autoradiography. These findings identify [68Ga]Ga-D-6-2-DMA as a promising lead radiotracer for further development.