Development of a 68 Ga-labelled PET tracer for carbonic anhydrase IX-overexpressed tumors using the artificial sweetener saccharin

Abstract

In this study, we developed a saccharin (SAC)-based radiopharmaceutical (⁶⁸ Ga-NOTA-SAC) and evaluated the possibility of its application as a PET tracer in the diagnosis of carbonic anhydrase IX (CA IX)-overexpressed tumors. We did a water-soluble tetrazolium assay and flow cytometry analysis to identify the cell viability decrease by SAC. The radiochemical purity and stability of ⁶⁸ Ga- NOTA-SAC in human and mouse serum was greater than 98%. The small animal PET image-based radioactivity distribution of all organs decreased over time.⁶⁸ Ga-NOTA-SAC presented the highest tumor-to-muscle ratio at 90 min post injection (p.i). The growth rates of tumor-to-muscle ratios of ⁶⁸ Ga-NOTA-SAC were 88% at 60 min and 220% at 90 min, compared to 30 min p.i. The potential of ⁶⁸ Ga-NOTA-SAC as a PET tracer is expected to contribute to the diagnostic research on CA IX-overexpressed tumors with the advantages of a relatively simple synthesis method.

Keywords: 68Ga-NOTA-SAC; Carbonic anhydrase IX; PET tracer; Saccharin; U87MG.