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

Shiou Shiow Farn, Kang Wei Chang, Wan Chi Lin, Hung Man Yu, Kun Liang Lin, Yu Chin Tseng, Yu Chang, Chung Shan Yu, Wuu Jyh Lin

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2577-2591
Number of pages15
JournalDrug Design, Development and Therapy
Volume15
DOIs
Publication statusPublished - 2021

Keywords

  • Dopamine transporter
  • Ga-68
  • Parkinson disease

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Synthesis, radiolabeling, and preliminary in vivo evaluation of [68ga] ipcat-nota as an imaging agent for dopamine transporter'. Together they form a unique fingerprint.

Cite this