In vitro and in vivo comparative study of Ga-68-labeled DOTA-, NOTA-, and HBEDCC-chelated radiotracers targeting prostate-specific membrane antigen

Ga-68-radiolabeled small molecules targeting prostate-specific membrane antigen (PSMA) have been extensively investigated as Ga-68-positron emission tomography (Ga-68-PET) tracers. Nevertheless, current Ga-68-labeled radiotracers suffer from either fair detection rates for metastatic prostate cancer lesions or a high uptake by the kidneys. This study synthesizes new PSMA-targeted radiotracers, [Ga-68]SC691-DOTA, [Ga-68]SC691-NOTA, and [Ga-68]SC691-HBEDCC, and explores the in vitro and in vivo properties. These three radiotracers enabled PSMA-positive LNCaP tumors to be visualized by micro-PET/CT as early as 5 min post-injection. Biodistribution studies revealed that all three compounds could accumulate in the tumor with high affinity. The kidney's uptake of [Ga-68]SC691-DOTA and [Ga-68]SC691-NOTA was comparable but lower than [Ga-68]SC691-HBEDCC. [Ga-68]SC691-HBEDCC demonstrated the most increased uptake and retention in the tumor over 2 h post-injection and a lower tumor-to-tissue ratio than [Ga-68]SC691-DOTA, and [Ga-68]SC691-NOTA.

Automated summary

This study synthesizes new PSMA-targeted radiotracers and finds that these three compounds can visualize PSMA-positive LNCaP tumors as early as 5 min post-injection. All three compounds have high affinity for the tumor. Among them, [Ga-68]SC691-HBEDCC shows the highest uptake and retention in the tumor over 2 h post-injection and a lower tumor-to-tissue ratio compared to [Ga-68]SC691-DOTA and [Ga-68]SC691-NOTA.