Synthesis, radiolabeling, and preliminary in vivo evaluation of [⁶⁸ga] ipcat-nota as an imaging agent for dopamine transporter

Introduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [^99mTc]TRODAT-1, [¹²³I]β-CIT, and [¹²³I]FP-CIT are commercially available;⁹⁹Mo/^99mTc generator is in short supply and¹²³I 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 chelating⁶⁸Ga, a radioisotope derived from a⁶⁸Ge/⁶⁸Ga generator. Methods: IPCAT-NOTA 22 was synthesized and labeled with [⁶⁸Ga]GaCl₄ − at room tem-perature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodis-tribution, and dynamic PET imaging studies were performed in Sprague Dawley rats. Results: [⁶⁸Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [⁶⁸Ga]IPCAT-NOTA 24 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 [⁶⁸Ga]IPCAT-NOTA 24 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 [⁶⁸Ga]IPCAT-NOTA 24 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 [⁶⁸Ga]IPCAT-NOTA 24 uptake and transporter localization.