Synthesis, Radiolabeling, and Preliminary in vivo Evaluation of [Ga] IPCAT-NOTA as an Imaging Agent for Dopamine Transporter.

INTRODUCTION

Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [Tc]TRODAT-1, [I]β-CIT, and [I]FP-CIT are commercially available; Mo/Tc generator is in short supply and I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating Ga, a radioisotope derived from a Ge/Ga generator.

METHODS

IPCAT-NOTA was synthesized and labeled with [Ga]GaCl at room temperature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodistribution, and dynamic PET imaging studies were performed in Sprague Dawley rats.

RESULTS

[Ga]IPCAT-NOTA obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [Ga]IPCAT-NOTA of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100- and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [Ga]IPCAT-NOTA showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5-15, 30-40, and 60-70 minutes, respectively, in NanoPET studies. The RCP% of [Ga]IPCAT-NOTA at 30 minutes in vivo remained 67.65%.

CONCLUSION

Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [Ga]IPCAT-NOTA uptake and transporter localization.