Effects of ⁶⁸Ga-labeled PEG and non-PEG variant peptides as HER2-targeting probes on the progression of gastrointestinal (GI) tumor cells

Human epidermal growth factor receptor 2 (HER2)-targeted molecular probes have great application prospects in the diagnosis of various cancers, including gastrointestinal (GI) cancer.

This study aimed to investigate the effects of ⁶⁸Ga-labeled PEG and non-PEG variant peptides on GI cancer.

The results showed that HER2 is overexpressed in GC and CRC. ⁶⁸Ga-DOTA-A9 and ⁶⁸Ga-DOTA-PEG₄-A9 were prepared with high radiochemical purity (> 95%), and it was stable in saline at room temperature for 3 h. In vivo, probes specifically label tumor cells. ⁶⁸Ga-DOTA-PEG₄-A9 has higher hydrophilicity (log P = − 3.25 ± 0.14). Biodistribution studies demonstrated that ⁶⁸Ga-DOTA-A9 and ⁶⁸Ga-DOTA-PEG₄-A9 were rapidly cleared from blood and mainly excreted from the kidney. In vitro cell experiments have confirmed that ⁶⁸Ga-DOTA-A9 and ⁶⁸Ga-DOTA-PEG₄-A9 could activate the PI3K/AKT pathway by inhibiting the expression of HER2.

⁶⁸Ga-DOTA-A9 and ⁶⁸Ga-DOTA-PEG₄-A9 were easily synthesized, and it might be potential molecular probes for GI tumor, and could activate the PI3K/AKT pathway by inhibiting the expression of HER2, thereby regulating the progression of GI cancer.