Synthesis, radiolabeling, and pre-clinical evaluation of [Sc]Sc-AAZTA conjugate PSMA inhibitor, a new tracer for high-efficiency imaging of prostate cancer.

Purpose: The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer.

Background: Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [Sc][Sc-(AAZTA)] and two derivatives, i.e., [Sc][Sc (CNAAZTA-BSA)] and [Sc][Sc (CNAAZTA-cRGDfK)].

Results: B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes.

Conclusions: This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.