⁶⁸Ga-cyc-DX600 PET/CT in ACE2-targeted tumor imaging

For the tumor-specific ACE2 expression, this research aimed to establish and verify ACE2-targeted PET imaging in differentiating tumors with distinct ACE2 expression.

⁶⁸Ga-cyc-DX600 was synthesized as tracer of ACE2 PET. NOD-SCID mice were used to prepare the subcutaneous tumor models with HEK-293 or HEK-293T/hACE2 cells to verify ACE2 specificity, with other kinds of tumor cells to evaluate the diagnostic efficiency for ACE2 expression, additionally, immunohistochemical analysis and western blot were used to certify the findings on ACE2 PET, which was then performed on four cancer patients and compared with FDG PET.

The metabolic clearance of ⁶⁸Ga-cyc-DX600 was initially completed in 60 min, realizing an ACE2-dependent and organ-specific background of ACE2 PET; meanwhile, tracer uptake of subcutaneous tumor models was of a definite dependence on ACE2 expression (r = 0.903, p < 0.05), and the latter served as the primary factor when ACE2 PET was used for the differential diagnosis of ACE2-related tumors. In pre-clinical practice, a comparable tumor-to-background ratio was acquired in ACE2 PET of a lung cancer patient at 50 and 80 min post injection; the quantitative values of ACE2 PET and FDG PET were negatively correlated (r =  - 0.971 for SUV_max, p = 0.006; r =  - 0.994 for SUV_mean, p = 0.001) in an esophageal cancer patient, no matter the primary lesion or metastasis.

⁶⁸Ga-cyc-DX600 PET was an ACE2-specific imaging for the differential diagnosis of tumors and added complementary value to conventional nuclear medicine diagnosis, such as FDG PET on glycometabolism.