Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Evaluation of 64Cu-labeled PET Tracers for Imaging Acute Inflammation and Endogenous Hydrogen Sulfide

  • Hye Yeon Seo (Department of Biomedical Sciences, Seoul National University Graduate School) ;
  • Ran Ji Yoo (Department of Nuclear Medicine, Seoul National University Hospital) ;
  • Jae min Jeong (Cellbion Co., Ltd.) ;
  • Yun-sang Lee (Department of Nuclear Medicine, Seoul National University Hospital)
  • Received : 2023.12.08
  • Accepted : 2023.12.26
  • Published : 2023.12.30
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Abstract

Hydrogen sulfide (H2S), recognized as the third gasotransmitter with specific implications for inflammation and hypoxia, exhibits affinity for 64Cu immobilization. This study explores the viability of 64Cu-labeled PET tracers in detecting endogenous H2S. In vitro reactivity experiments involved evaluating the interaction between various concentrations of NaHS and 64Cu-labeled chelators at 37℃ in a shaking incubator. In vivo molecular PET imaging studies were conducted using two distinct mouse models. An acute inflammation model, induced with carrageenan, involved administering 2.22 MBq/100 µL of [64Cu]Cu-ATSM or [64Cu]Cu-Cyclen intravenously 4 hours post-inflammation induction, with subsequent PET imaging in static 5 min mode. For the NaHS implantation model, NaHS dissolved in Matrigel was subcutaneously injected into the right dorsal region of BALB/c mice, followed by intravenous injection of radiotracers (2.22 MBq/100 µL) 1 hour later, and subsequent PET imaging. The optimized labeling condition involved dissolving 10 ㎍ of chelators in ammonium acetate buffer and reacting at 60℃ for 20 minutes. Both [64Cu]Cu-Cyclen and [64Cu]Cu-ATSM reacted with various concentrations of NaHS to form insoluble 64CuS. High uptake of [64Cu]Cu-ATSM and [64Cu]Cu-Cyclen in acute inflammatory lesions in the mouse right footpad and the NaHS implantation model suggests their potential as imaging agents for inflammation and H2S in vivo. In conclusion, optimized [64Cu]Cu-ATSM and [64Cu]Cu-Cyclen labeling conditions for endogenous H2S imaging were established, confirming insoluble 64CuS both in vitro and in vivo. [64Cu]Cu-ATSM and [64Cu]Cu-Cyclen hold promise as diagnostic agents targeting endogenous H2S in various diseases associated with inflammation and hypoxia.

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Acknowledgement

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