Synthesis and biological evaluation of 68Ga-DOTA-AngII as a radiotracer for PET/MR imaging of hepatocellular carcinoma

The precise diagnosis of HCC is confronted with severe challenges due to the tumor heterogeneity and insidious symptoms of hepatocellular carcinoma (HCC), and meanwhile the limitations of positron emission tomography (PET) with traditional 2-deoxy-2-[fluorine-18] fluoro-d-glucose (¹⁸F-FDG) tracer. Given that angiotensin II type 1 receptor (AT1R) is significantly upregulated in HCC and closely related to its progression, we have developed a novel ⁶⁸Ga-radiolabeled compound, ⁶⁸Ga-DOTA-AngII (⁶⁸Ga-DOTA-GGDRVYIHPF), and evaluated its HCC detection capability. ⁶⁸Ga-DOTA-AngII demonstrated acceptable stability in both human plasma and phosphate buffered saline. In vivo imaging and in vitro biodistribution analysis in tumor-bearing mice showed that ⁶⁸Ga-DOTA-AngII demonstrate a high tumor uptake, and the tumor tissue exhibited rapid uptake. In brief, this radiotracer possesses a promising potency for imaging the expression of AT1R for further clinical application.