Development and biological evaluation of PSMA/FAP dual targeting radiotracers for prostate cancer imaging†

Prostate cancer (PCa) is a common malignant cancer in men with a five-year survival rate of 32%. In recent years, positron emission tomography (PET) has been widely used in clinical PCa diagnosis. In this study, we developed two novel PSMA-FAP radiotracers ([⁶⁸Ga]Ga-PSMA-FAPI-01 and [⁶⁸Ga]Ga-PSMA-FAPI-02) for PET/CT, aiming to develop PSMA-FAP dual-targeting radiotracers with high selectivity and favourable pharmacokinetic properties for the diagnosis of PCa. We introduced lipophilic groups, based on the glutamic acid–urea–lysine pharmacophore and linked a DOTAGA group for ⁶⁸Ga labeling. [⁶⁸Ga]Ga-PSMA-FAPI-01 and [⁶⁸Ga]Ga-PSMA-FAPI-02 were investigated, compared with [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-PSMA I&T. Two novel radiotracers were prepared with a radiochemical purity >95%, and excellent stability in vivo and in vitro. Novel radiotracers revealed high receptor affinity towards PSMA and FAP (K_i < 10 nM). The results of micro-PET/CT imaging and biodistribution studies demonstrated that novel radiotracers displayed excellent dual-targeting capability and favorable pharmacokinetic properties, which were also observed in human PET/CT studies. All these indicate that a dual-targeting strategy is available in designing radiotracers for tumor imaging.