68Ga-TP1580 as a novel molecular probe for HER2-positive tumor imaging using MicroPET

HER2 is an attractive target for the treatment of breast cancer. Tc-99(m)-labeled HER2-specific binding to the small molecule mimetic peptide B2-S22-AFA shows the potential of detecting HER2 expression in vivo (Zhang in Transl Oncol 10:518-526, 2017). However, the low resolution of SPECT-CT imaging and the inability to quantitatively analyze may partially limit its wide use.Ga-68 is an excellent PET radionuclide due to availability, nearly quantitative reaction, and short physical half-life. In this study, Ga-68-labeled-NOTA- B2-S22-AFA (hereinafter referred to as Ga-68-TP1580) was applied for PET-CT imaging in HER2 breast cancer xenografts mice. In vitro studies and MicroPET imaging were performed in the SKBR-3 breast cancer model. Ga-68-TP1580 could be produced within 20 min with 93.2 +/- 2.1% yield and the radiochemical purity was greater than 95%. The tracer was stable in PBS and human serum for at least 2 h. MicroPET imaging revealed that the SKBR-3 xenografts were visualized and the tumor uptakes were 1.22 +/- 0.04, 0.71 +/- 0.07, and 0.43 +/- 0.04% ID/g at 0.5 h, 1 h, and 2 h.The corresponding tumor-to-blood and tumor-to-muscle ratios were 1.05 +/- 0.06, 1.34 +/- 0.21, and 1.33 +/- 0.57, respectively, and 4.02 +/- 1.39, 7.47 +/- 2.86, and 5.82 +/- 1.98 at 0.5 h, 1 h, and 2 h. No significant decrease in tumor uptake of Ga-68-TP1580 was seen after injection of excess unlabeled TP1580.In conclusion, TP1580 can be labeled by Ga-68 with high radiochemical purity (> 95%), good vitro stability (keep consistent radiochemical purity > 95% for more than 2 h).Ga-68-TP1580 can combine with target tissue and show some tumor uptake in SKBR-3 xenografts, but not be blocked by NOTA-B2-S22-AFA which indicates poor specificity.