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

Imaging diagnosis of inflammation has been challenging for many years. Inflammation imaging agents commonly used in nuclear medicine, such as [⁶⁷Ga]Ga-citrate and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) showed some limitations. The identification of a radiotracer with high specificity and low radiation dose is clinically important. With the commercialization of ⁶⁸Ge/⁶⁸Ga generators and the high ⁶⁸Ga cyclotron production capacity, the study of ⁶⁸Ga-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 ⁶⁸Ga complexation and as a new positron emission tomography (PET) imaging agent of inflammation in comparison to [⁶⁸Ga]Ga-citrate.

The present experimental studies have shown that the novel [⁶⁸Ga]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 [⁶⁸Ga]Ga-4HMSA displayed similar uptakes in the inflamed paw than [⁶⁸Ga]Ga-citrate, which are superior compared to those of contralateral (non-injected) paws at days 1-3 from PET imaging. [⁶⁸Ga]Ga-citrate accumulated in the upper body of the animal such as the liver, lungs and the heart, whereas the [⁶⁸Ga]Ga-4HMSA revealed low uptakes in the majority of the organs and was cleared relatively rapidly from blood circulation through the kidneys and bladder.

The results highlight the potential of [⁶⁸Ga]Ga-4HMSA as an interesting alternative to [⁶⁸Ga]Ga-citrate for inflammation imaging by PET. The new PET tracer also offers additional advantages than [⁶⁸Ga]Ga-citrate in term of dosimetry and lower overall background activity.