[(68)Ga]Ga-4HMSA a promising new PET tracer for imaging inflammation

BACKGROUND: Imaging diagnosis of inflammation has been challenging for many years. Inflammation imaging agents commonly used in nuclear medicine, such as [(67)Ga]Ga-citrate and 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) showed some limitations. The identification of a radiotracer with high specificity and low radiation dose is clinically important. With the commercialization of (68)Ge/(68)Ga generators and the high (68)Ga cyclotron production capacity, the study of (68)Ga-based tracer for inflammation has increased and shown good potential. In the present work, we report the synthesis of 4HMSA, a new acyclic chelator, and its first investigation for (68)Ga complexation and as a new positron emission tomography (PET) imaging agent of inflammation in comparison to [(68)Ga]Ga-citrate. RESULTS: The present experimental studies have shown that the novel [(68)Ga]Ga-4HMSA is stable allowing imaging of inflammation in a preclinical model of adjuvant- and pathogen-based inflammation involving intraplantar injection of complete Freund’s adjuvant (CFA). We also found that [(68)Ga]Ga-4HMSA displayed similar uptakes in the inflamed paw than [(68)Ga]Ga-citrate, which are superior compared to those of contralateral (non-injected) paws at days 1–3 from PET imaging. [(68)Ga]Ga-citrate accumulated in the upper body of the animal such as the liver, lungs and the heart, whereas the [(68)Ga]Ga-4HMSA revealed low uptakes in the majority of the organs and was cleared relatively rapidly from blood circulation through the kidneys and bladder. CONCLUSION: The results highlight the potential of [(68)Ga]Ga-4HMSA as an interesting alternative to [(68)Ga]Ga-citrate for inflammation imaging by PET. The new PET tracer also offers additional advantages than [(68)Ga]Ga-citrate in term of dosimetry and lower overall background activity.