⁶⁸Ga-DOTA-Neratinib: A novel small-molecule PET tracer for breast cancer imaging

Current DOTA-based ⁶⁸Ga-labeled small-molecule probes targeting HER2 often suffer from limited tumor-specific uptake. To overcome this limitation, we selected Neratinib, a second-generation pan-HER tyrosine kinase inhibitor, and successfully developed a novel PET imaging agent, ⁶⁸Ga-DOTA-Neratinib. The probe demonstrated high radiochemical yield, excellent in vitro and in vivo stability, and strong binding affinity for the HER2 receptor. Cell uptake assays confirmed specific accumulation in HER2-positive cell lines: uptake in BT-474 and SK-BR-3 cells at 2 h post-incubation was 7.55 ± 1.10 % and 8.18 ± 0.56 %, respectively, significantly higher than that in HER2-negative MCF-7 cells (4.71 ± 0.79 %, P < 0.05). Moreover, micro-PET/CT imaging in HER2-positive tumor-bearing mice showed enhanced tumor uptake and prolonged intratumoral retention of the tracer, though some background blood activity was also observed. These findings suggest that ⁶⁸Ga-DOTA-Neratinib is a promising small-molecule PET probe for the noninvasive imaging of HER2-positive breast cancer.