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@ARTICLE{Michno:274066,
      author       = {Michno, Manuel and Schmitz, Jan and Foerges, Anna L and
                      Beer, Simone and Jordan, Jens and Neumaier, Bernd and
                      Drzezga, Alexander and Aeschbach, Daniel and Bauer, Andreas
                      and Tank, Jens and Weis, Henning and Elmenhorst, Eva-Maria
                      and Elmenhorst, David},
      title        = {{E}ffect of {A}cute {H}ypoxia {E}xposure on the
                      {A}vailability of {A}1 {A}denosine {R}eceptors and
                      {P}erfusion in the {H}uman {B}rain.},
      journal      = {Journal of nuclear medicine},
      volume       = {66},
      number       = {1},
      issn         = {0097-9058},
      address      = {New York, NY},
      publisher    = {Soc.},
      reportid     = {DZNE-2025-00047},
      pages        = {142 - 149},
      year         = {2025},
      abstract     = {In animal studies it has been observed that the inhibitory
                      neuromodulator adenosine is released into the cerebral
                      interstitial space during hypoxic challenges. Adenosine's
                      actions on the A1 adenosine receptor (A1AR) protect the
                      brain from oxygen deprivation and overexertion through
                      adjustments in cerebral blood flow, metabolism, and electric
                      activity. Methods: Using
                      8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine
                      ([18F]CPFPX), a PET tracer for the A1AR, we tested the
                      hypothesis that hypoxia-induced adenosine release reduces
                      A1AR availability in the human brain. Furthermore, we
                      investigated whether this response is associated with
                      altered brain perfusion and psychomotor vigilance. Ten
                      healthy volunteers completed a 110-min
                      bolus-plus-constant-infusion [18F]CPFPX PET/MRI hybrid
                      experiment including a 30-min interval of normobaric hypoxia
                      with peripheral oxygen saturation between $70\%$ and $75\%.$
                      We obtained blood samples to calculate metabolite-corrected
                      steady-state A1AR distribution volumes and measured gray
                      matter brain perfusion via arterial spin labeling in high
                      temporal resolution. A 3-min psychomotor vigilance test was
                      conducted every 10 min, and heart rate and peripheral blood
                      oxygen saturation were continuously measured. Results: In
                      all 7 examined brain regions, hypoxia reduced A1AR
                      availability significantly (e.g., frontal lobe, $13.5\%;$ P
                      = 0.0144) whereas gray matter brain perfusion increased
                      (e.g., frontal lobe, $42.5\%;$ P = 0.0007). Heart rate
                      increased by $19\%$ (P = 0.0039). Mean reaction speed
                      decreased by $4.3\%$ (P = 0.0021). Conclusion: Our study is
                      the first, to our knowledge, to demonstrate that acute
                      hypoxia, corresponding to a mean altitude of 5,500 m (18,000
                      ft), reduces A1AR availability in the human brain. The
                      finding is consistent with hypoxia-induced cerebral
                      adenosine release leading to increased A1AR occupancy.},
      keywords     = {Humans / Male / Receptor, Adenosine A1: metabolism / Adult
                      / Brain: diagnostic imaging / Brain: metabolism / Brain:
                      blood supply / Female / Positron-Emission Tomography /
                      Cerebrovascular Circulation / Hypoxia: metabolism / Hypoxia:
                      physiopathology / Hypoxia: diagnostic imaging / Young Adult
                      / Xanthines / Magnetic Resonance Imaging / A1AR (Other) /
                      ASL (Other) / PET (Other) / [18F]CPFPX (Other) / adenosine
                      receptors (Other) / hypoxia (Other) / Receptor, Adenosine A1
                      (NLM Chemicals) / Xanthines (NLM Chemicals) /
                      8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine (NLM
                      Chemicals)},
      cin          = {AG Boecker},
      ddc          = {610},
      cid          = {I:(DE-2719)1011202},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39667818},
      doi          = {10.2967/jnumed.124.268455},
      url          = {https://pub.dzne.de/record/274066},
}