Skip to main content

Advertisement

SpringerLink
Log in

In vivo detection of hydrogen sulfide in the brain of live mouse: application in neuroinflammation models

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

An Editorial to this article was published on 03 August 2022

Abstract

Purpose

Hydrogen sulfide (H2S) plays important roles in brain pathophysiology. However, nuclear imaging probes for the in vivo detection of brain H2S in living animals have not been developed. Here, we report the first nuclear imaging probe that enables in vivo imaging of endogenous H2S in the brain of live mice.

Methods

Utilizing a bis(thiosemicarbazone) backbone, a fluorescent ATSM-FITC conjugate was synthesized. Its copper complex, Cu(ATSM-FITC) was thoroughly tested as a biosensor for H2S. The same ATSM-FITC ligand was quantitatively labeled with [64Cu]CuCl2 to obtain a radioactive [64Cu][Cu(ATSM-FITC)] imaging probe. Biodistribution and positron emission tomography (PET) imaging studies were performed in healthy mice and neuroinflammation models.

Results

The Cu(ATSM-FITC) complex reacts instantly with H2S to release CuS and becomes fluorescent. It showed excellent reactivity, sensitivity, and selectivity to H2S. Endogenous H2S levels in living cells were successfully detected by fluorescence microscopy. Exceptionally high brain uptake of [64Cu][Cu(ATSM-FITC)] (> 9% ID/g) was observed in biodistribution and PET imaging studies. Subtle changes in brain H2S concentrations in live mice were accurately detected by quantitative PET imaging. Due to its dual modality feature, increased H2S levels in neuroinflammation models were characterized at the subcellular level by fluorescence imaging and at the whole-body scale by PET imaging.

Conclusion

Our biosensor can be readily utilized to study brain H2S function in live animal models and shows great potential as a novel imaging agent for diagnosing brain diseases.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

AA:

Ascorbic acid

AOAA:

Aminooxyacetic acid

AP:

Anteroposterior

BBB:

Blood-brain barrier

CBS:

Cystathionine β-synthase

CO:

Carbon monoxide

CSE:

Cystathionine γ-lyase

Cys:

L-cysteine

DMSO:

Dimethyl sulfoxide

DTT:

Dithiothreitol

DV:

Dorsoventral

FBS:

Fetal bovine serum

FITC-NCS:

Fluorescein isothiocyanate

GSH:

Glutathione

H2O2 :

Hydrogen peroxide

H2S:

Hydrogen sulfide

Hcys:

L-homocysteine

HEK293:

Human embryonic kidney 293 cell

HeLa:

Human cervical cancer cell

HepG2:

Human liver cancer cell

HRMS:

High-resolution mass spectrometry

LPS:

Lipopolysaccharide

LOD:

Limit of detection

MIP:

Maximum intensity projection

ML:

Mediolateral

NO:

Nitric oxide

ONOO− :

Peroxynitrite

PBS:

Phosphate-buffered saline

PET:

Positron emission tomography

PPG:

DL-propargylglycine

U87MG:

Human brain glioblastoma cell

2-ME:

2-Mercaptoethanol

References

  1. Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 1996;16:1066–71. https://doi.org/10.1523/JNEUROSCI.16-03-01066.1996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cao X, Ding L, Xie ZZ, Yang Y, Whiteman M, Moore PK, et al. A review of hydrogen sulfide synthesis, metabolism, and measurement: is modulation of hydrogen sulfide a novel therapeutic for cancer? Antioxid Redox Signal. 2019;31:1–38. https://doi.org/10.1089/ars.2017.7058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nagpure BV, Bian JS. Brain, learning, and memory: role of H2S in neurodegenerative diseases. Handb Exp Pharmacol. 2015;230:193–215. https://doi.org/10.1007/978-3-319-18144-8_10.

    Article  CAS  PubMed  Google Scholar 

  4. Gong QH, Shi XR, Hong ZY, Pan LL, Liu XH, Zhu YZ. A new hope for neurodegeneration: possible role of hydrogen sulfide. J Alzheimers Dis. 2011;24(Suppl 2):173–82. https://doi.org/10.3233/JAD-2011-110128.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang JY, Ding YP, Wang Z, Kong Y, Gao R, Chen G. Hydrogen sulfide therapy in brain diseases: from bench to bedside. Med Gas Res. 2017;7:113–9. https://doi.org/10.4103/2045-9912.208517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bae SK, Heo CH, Choi DJ, Sen D, Joe EH, Cho BR, et al. A ratiometric two-photon fluorescent probe reveals reduction in mitochondrial H2S production in Parkinson’s disease gene knockout astrocytes. J Am Chem Soc. 2013;135:9915–23. https://doi.org/10.1021/ja404004v.

    Article  CAS  PubMed  Google Scholar 

  7. Giovinazzo D, Bursac B, Sbodio JI, Nalluru S, Vignane T, Snowman AM, et al. Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3b and inhibiting Tau hyperphosphorylation. Proc Natl Acad Sci USA. 2021;118:e2017225118. https://doi.org/10.1073/pnas.2017225118.

  8. Zhang X, Bian JS. Hydrogen sulfide: a neuromodulator and neuroprotectant in the central nervous system. ACS Chem Neurosci. 2014;5:876–83. https://doi.org/10.1021/cn500185g.

    Article  CAS  PubMed  Google Scholar 

  9. Wallace JL, Wang R. Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter. Nat Rev Drug Discov. 2015;14:329–45. https://doi.org/10.1038/nrd4433.

    Article  CAS  PubMed  Google Scholar 

  10. Kang JM, Li Z, Organ CL, Park CM, Yang CT, Pacheco A, et al. pH-Controlled hydrogen sulfide release for myocardial ischemia-reperfusion injury. J Am Chem Soc. 2016;138:6336–9. https://doi.org/10.1021/jacs.6b01373.

    Article  CAS  PubMed  Google Scholar 

  11. Ibrahim H, Serag A, Farag MA. Emerging analytical tools for the detection of the third gasotransmitter H2S, a comprehensive review. J Adv Res. 2021;27:137–53. https://doi.org/10.1016/j.jare.2020.05.018.

    Article  CAS  PubMed  Google Scholar 

  12. Lippert AR, New EJ, Chang CJ. Reaction-based fluorescent probes for selective imaging of hydrogen sulfide in living cells. J Am Chem Soc. 2011;133:10078–80. https://doi.org/10.1021/ja203661j.

    Article  CAS  PubMed  Google Scholar 

  13. Sasakura K, Hanaoka K, Shibuya N, Mikami Y, Kimura Y, Komatsu T, et al. Development of a highly selective fluorescence probe for hydrogen sulfide. J Am Chem Soc. 2011;133:18003–5. https://doi.org/10.1021/ja207851s.

    Article  CAS  PubMed  Google Scholar 

  14. Lin VS, Lippert AR, Chang CJ. Cell-trappable fluorescent probes for endogenous hydrogen sulfide signaling and imaging H2O2-dependent H2S production. Proc Natl Acad Sci U S A. 2013;110:7131–5. https://doi.org/10.1073/pnas.1302193110.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lin VS, Chen W, Xian M, Chang CJ. Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems. Chem Soc Rev. 2015;44:4596–618. https://doi.org/10.1039/c4cs00298a.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hammers MD, Taormina MJ, Cerda MM, Montoya LA, Seidenkranz DT, Parthasarathy R, et al. A bright fluorescent probe for H2S enables analyte-responsive, 3D imaging in live Zebrafish using light sheet fluorescence microscopy. J Am Chem Soc. 2015;137:10216–23. https://doi.org/10.1021/jacs.5b04196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shimamoto K, Hanaoka K. Fluorescent probes for hydrogen sulfide (H2S) and sulfane sulfur and their applications to biological studies. Nitric Oxide. 2015;46:72–9. https://doi.org/10.1016/j.niox.2014.11.008.

    Article  CAS  PubMed  Google Scholar 

  18. Pak YL, Li J, Ko KC, Kim G, Lee JY, Yoon J. Mitochondria-targeted reaction-based fluorescent probe for hydrogen sulfide. Anal Chem. 2016;88:5476–81. https://doi.org/10.1021/acs.analchem.6b00956.

    Article  CAS  PubMed  Google Scholar 

  19. Peng JJ, Teoh CL, Zeng X, Samanta A, Wang L, Xu W, et al. Development of a highly selective, sensitive, and fast response upconversion luminescent platform for hydrogen sulfide detection. Adv Funct Mater. 2016;26:191–9. https://doi.org/10.1002/adfm.201503715.

    Article  CAS  Google Scholar 

  20. Sarkar S, Ha YS, Soni N, An GI, Lee W, Kim MH, et al. Immobilization of the gas signaling molecule H2S by radioisotopes: detection, quantification, and in vivo imaging. Angew Chem Int Ed. 2016;55:9365–70. https://doi.org/10.1002/anie.201603813.

    Article  CAS  Google Scholar 

  21. Krasnovskaya O, Spector D, Zlobin A, Pavlov K, Gorelkin P, Erofeev A, et al. Metals in imaging of Alzheimer’s disease. Int J Mol Sci. 2020;21:9190. https://doi.org/10.3390/ijms21239190.

  22. McInnes LE, Noor A, Kysenius K, Cullinane C, Roselt P, McLean CA, et al. Potential diagnostic imaging of Alzheimer’s disease with copper-64 complexes that bind to amyloid-beta plaques. Inorg Chem. 2019;58:3382–95. https://doi.org/10.1021/acs.inorgchem.8b03466.

    Article  CAS  PubMed  Google Scholar 

  23. Noor A, Hayne DJ, Lim S, Van Zuylekom JK, Cullinane C, Roselt PD, et al. Copper bis(thiosemicarbazonato)-stilbenyl complexes that bind to amyloid-beta plaques. Inorg Chem. 2020;59:11658–69. https://doi.org/10.1021/acs.inorgchem.0c01520.

    Article  CAS  PubMed  Google Scholar 

  24. Paterson BM, Cullinane C, Crouch PJ, White AR, Barnham KJ, Rose PD, et al. Modification of biodistribution and brain uptake of copper bis(thiosemicarbazonato) complexes by the incorporation of amine and polyamine functional groups. Inorg Chem. 2019;58:4540–52. https://doi.org/10.1021/acs.inorgchem.9b00117.

    Article  CAS  PubMed  Google Scholar 

  25. Paterson BM, Donnelly PS. Copper complexes of bis(thiosemicarbazones): from chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals. Chem Soc Rev. 2011;40:3005–18. https://doi.org/10.1039/c0cs00215a.

    Article  CAS  PubMed  Google Scholar 

  26. Singh NK, Kumbhar AA, Pokharel YR, Yadav PN. Anticancer potency of copper(II) complexes of thiosemicarbazones. J Inorg Biochem. 2020;210: 111134. https://doi.org/10.1016/j.jinorgbio.2020.111134.

    Article  CAS  PubMed  Google Scholar 

  27. Vavere AL, Lewis JS. Cu-ATSM: a radiopharmaceutical for the PET imaging of hypoxia. Dalton Trans. 2007;43:4893–902. https://doi.org/10.1039/b705989b.

  28. Andreozzi EM, Torres JB, Sunassee K, Dunn J, Walker-Samuel S, Szanda I, et al. Studies of copper trafficking in a mouse model of Alzheimer’s disease by positron emission tomography: comparison of 64Cu acetate and 64CuGTSM. Metallomics. 2017;9:1622–33. https://doi.org/10.1039/c7mt00227k.

    Article  CAS  PubMed  Google Scholar 

  29. Hickey JL, Lim S, Hayne DJ, Paterson BM, White JM, Villemagne VL, et al. Diagnostic imaging agents for Alzheimer’s disease: copper radiopharmaceuticals that target abeta plaques. J Am Chem Soc. 2013;135:16120–32. https://doi.org/10.1021/ja4057807.

    Article  CAS  PubMed  Google Scholar 

  30. Takano Y, Shimamoto K, Hanaoka K. Chemical tools for the study of hydrogen sulfide (H2S) and sulfane sulfur and their applications to biological studies. J Clin Biochem Nutr. 2016;58:7–15. https://doi.org/10.3164/jcbn.15-91.

    Article  CAS  PubMed  Google Scholar 

  31. Holland JP, Aigbirhio FI, Betts HM, Bonnitcha PD, Burke P, Christlieb M, et al. Functionalized bis(thiosemicarbazonato) complexes of zinc and copper: synthetic platforms toward site-specific radiopharmaceuticals. Inorg Chem. 2007;46:465–85. https://doi.org/10.1021/ic0615628.

    Article  CAS  PubMed  Google Scholar 

  32. Sarkar S, Bhatt N, Ha YS, Huynh PT, Soni N, Lee W, et al. High in vivo stability of 64Cu-labeled cross-bridged chelators is a crucial factor in improved tumor imaging of RGD peptide conjugates. J Med Chem. 2018;61:385–95. https://doi.org/10.1021/acs.jmedchem.7b01671.

    Article  CAS  PubMed  Google Scholar 

  33. Zhao J, Chen J, Ma S, Liu Q, Huang L, Chen X, et al. Recent developments in multimodality fluorescence imaging probes. Acta Pharm Sin B. 2018;8:320–38. https://doi.org/10.1016/j.apsb.2018.03.010.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Xi L, Jiang H. Image-guided surgery using multimodality strategy and molecular probes. WIREs Nanomed Nanobiotechnol. 2016;8:46–60. https://doi.org/10.1002/wnan.1352.

    Article  Google Scholar 

  35. Velusamy N, Binoy A, Bobba KN, Nedungadi D, Mishra N, Bhuniya S. A bioorthogonal fluorescent probe for mitochondrial hydrogen sulfide: new strategy for cancer cell labeling. Chem Commun. 2017;53:8802–5. https://doi.org/10.1039/c7cc05339h.

    Article  CAS  Google Scholar 

  36. Chen H, Gong X, Liu X, Li Z, Zhang J, Yang X-F. A nitroso-based fluorogenic probe for rapid detection of hydrogen sulfide in living cells. Sens Actuators B Chem. 2019;281:542–8. https://doi.org/10.1016/j.snb.2018.10.086.

    Article  CAS  Google Scholar 

  37. Magde D, Wong R, Seybold PG. Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and fluorescein in nine solvents: improved absolute standards for quantum yields. Photochem Photobiol. 2002;75:327–34. https://doi.org/10.1562/0031-8655(2002)075%3c0327:Fqyatr%3e2.0.Co;2.

    Article  CAS  PubMed  Google Scholar 

  38. Paul BD, Snyder SH, Kashfi K. Effects of hydrogen sulfide on mitochondrial function and cellular bioenergetics. Redox Biol. 2021;38:101772. https://doi.org/10.1016/j.redox.2020.101772.

  39. Carter RN, Morton NM. Cysteine and hydrogen sulphide in the regulation of metabolism: insights from genetics and pharmacology. J Pathol. 2016;238:321–32. https://doi.org/10.1002/path.4659.

    Article  CAS  PubMed  Google Scholar 

  40. Sun Q, Collins R, Huang S, Holmberg-Schiavone L, Anand GS, Tan CH, et al. Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H2S. J Biol Chem. 2009;284:3076–85. https://doi.org/10.1074/jbc.M805459200.

    Article  CAS  PubMed  Google Scholar 

  41. Wu Z, Liang D, Tang X. Visualizing hydrogen sulfide in mitochondria and lysosome of living cells and in tumors of living mice with positively charged fluorescent chemosensors. Anal Chem. 2016;88:9213–8. https://doi.org/10.1021/acs.analchem.6b02459.

    Article  CAS  PubMed  Google Scholar 

  42. Kim JY, Sarkar S, Bobba KN, Huynh PT, Bhise A, Yoo J. Development of dansyl based copper(II) complex to detect hydrogen sulfide in hypoxia. Org Biomol Chem. 2019;17:7088–94. https://doi.org/10.1039/c9ob00948e.

    Article  CAS  PubMed  Google Scholar 

  43. Pajouhesh H, Lenz GR. Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2005;2:541–53. https://doi.org/10.1602/neurorx.2.4.541.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yang J, Minkler P, Grove D, Wang R, Willard B, Dweik R, et al. Non-enzymatic hydrogen sulfide production from cysteine in blood is catalyzed by iron and vitamin B6. Commun Biol. 2019;2:194. https://doi.org/10.1038/s42003-019-0431-5.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Akahoshi N, Kamata S, Kubota M, Hishiki T, Nagahata Y, Matsuura T, et al. Neutral aminoaciduria in cystathionine beta-synthase-deficient mice; an animal model of homocystinuria. Am J Physiol Renal Physiol. 2014;306:F1462–76. https://doi.org/10.1152/ajprenal.00623.2013.

    Article  CAS  PubMed  Google Scholar 

  46. Lewis JS, McCarthy DW, McCarthy TJ, Fujibayashi Y, Welch MJ. Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model. J Nucl Med. 1999;40:177–83.

    CAS  PubMed  Google Scholar 

  47. Asimakopoulou A, Panopoulos P, Chasapis CT, Coletta C, Zhou ZM, Cirino G, et al. Selectivity of commonly used pharmacological inhibitors for cystathionine synthase (CBS) and cystathionine lyase (CSE). Brit J Pharmacol. 2013;169:922–32. https://doi.org/10.1111/bph.12171.

    Article  CAS  Google Scholar 

  48. Shatalin K, Nuthanakanti A, Kaushik A, Shishov D, Peselis A, Shamovsky I, et al. Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance. Science. 2021;372:1169–75. https://doi.org/10.1126/science.abd8377.

    Article  CAS  PubMed  Google Scholar 

  49. Moest RR. Hydrogen sulfide determination by the methylene blue method. Anal Chem. 1975;47:1204–5. https://doi.org/10.1021/ac60357a008.

    Article  CAS  Google Scholar 

  50. Savelieff MG, Lee S, Liu Y, Lim MH. Untangling amyloid-beta, tau, and metals in Alzheimer’s disease. ACS Chem Biol. 2013;8:856–65. https://doi.org/10.1021/cb400080f.

    Article  CAS  PubMed  Google Scholar 

  51. Jassam YN, Izzy S, Whalen M, McGavern DB, El Khoury J. Neuroimmunology of traumatic brain injury: Time for a paradigm shift. Neuron. 2017;95:1246–65. https://doi.org/10.1016/j.neuron.2017.07.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease Nat Rev Dis Primers. 2017;3:17013. https://doi.org/10.1038/nrdp.2017.13.

    Article  PubMed  Google Scholar 

  53. Jayaraj RL, Azimullah S, Beiram R, Jalal FY, Rosenberg GA. Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation. 2019;16:142. https://doi.org/10.1186/s12974-019-1516-2.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Chun H, Im H, Kang YJ, Kim Y, Shin JH, Won W, et al. Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2- production. Nat Neurosci. 2020;23:1555–66. https://doi.org/10.1038/s41593-020-00735-y.

    Article  CAS  PubMed  Google Scholar 

  55. Hong J, Yoon D, Nam Y, Seo D, Kim JH, Kim MS, et al. Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation. Sci Rep. 2020;10:13337. https://doi.org/10.1038/s41598-020-70390-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Jha MK, Jeon S, Jin M, Ock J, Kim JH, Lee WH, et al. The pivotal role played by lipocalin-2 in chronic inflammatory pain. Exp Neurol. 2014;254:41–53. https://doi.org/10.1016/j.expneurol.2014.01.009.

    Article  CAS  PubMed  Google Scholar 

  57. Tao H, Guo J, Ma Y, Zhao Y, Jin T, Gu L, et al. Luminescence imaging of acute liver injury by biodegradable and biocompatible nanoprobes. ACS Nano. 2020;14:11083–99. https://doi.org/10.1021/acsnano.0c00539.

    Article  CAS  PubMed  Google Scholar 

  58. Kumar M, Sandhir R. Hydrogen Sulfide in physiological and pathological mechanisms in brain. CNS Neurol Disord Drug Targets. 2018;17:654–70. https://doi.org/10.2174/1871527317666180605072018.

    Article  CAS  PubMed  Google Scholar 

  59. Eto K, Asada T, Arima K, Makifuchi T, Kimura H. Brain hydrogen sulfide is severely decreased in Alzheimer’s disease. Biochem Biophys Res Commun. 2002;293:1485–8. https://doi.org/10.1016/S0006-291X(02)00422-9.

    Article  CAS  PubMed  Google Scholar 

  60. DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139(Suppl 2):136–53. https://doi.org/10.1111/jnc.13607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Pizza V, Agresta A, D’Acunto CW, Festa M, Capasso A. Neuroinflamm-aging and neurodegenerative diseases: an overview. CNS Neurol Disord Drug Targets. 2011;10:621–34. https://doi.org/10.2174/187152711796235014.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The Korea Basic Science Institute is acknowledged for HRMS measurements.

Funding

This work was supported by the R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Nos. 2020M2D8A3094031, 2019R1A2C2084313, 2017R1A5A2015391, and 2019H1D3A1A01102643). This work was also supported by a grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by MSIT, Republic of Korea (No. 50461–2022).

Author information

Author notes

  1. Bora Nam, Woonghee Lee, and Swarbhanu Sarkar contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea

    Bora Nam, Woonghee Lee, Swarbhanu Sarkar, Abhinav Bhise, Phuong Tu Huynh, Subramani Rajkumar, Kiwoong Lee, Yeong Su Ha, Seong Hwan Cho, Jeong Eun Lim, Kyung Won Kim & Jeongsoo Yoo

  2. Department of Pharmacology, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Brain Science & Engineering Institute, Kyungpook National University, Daegu, 41944, South Korea

    Jae-Hong Kim & Kyoungho Suk

  3. Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, South Korea

    Hyun Park, Jung Young Kim & Kyo Chul Lee

Authors
  1. Bora Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Woonghee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Swarbhanu Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jae-Hong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abhinav Bhise
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jung Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Phuong Tu Huynh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Subramani Rajkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kiwoong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yeong Su Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Seong Hwan Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jeong Eun Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kyung Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kyo Chul Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Kyoungho Suk
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jeongsoo Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.Y. conceived and directed the project. J.Y., B.N., W.L., and S.S. designed the experiments. S.S. performed organic synthesis. S.S., A.B., P.T.H., and S.R. performed all radiochemistry works. B.N., W.L., K.L., Y.S.H., J.E.L., and K.W.K. performed imaging and biodistribution studies. B.N., S.H.C., and W.L. performed all of the biological evaluation experiments. H.P., J.Y.K., and K.C.L. produced the Cu-64 isotope. J.-H.K. and K.S. performed neuroinflammation studies. B.N., W.L., S.S., J.-H.K., and J.Y. wrote the manuscript in close collaboration with the other coauthors.

Corresponding author

Correspondence to Jeongsoo Yoo.

Ethics declarations

Ethics approval

All animal experiments were performed according to approved animal protocols and guidelines established by the Animal Care Committee of Kyungpook National University (No. KNU 2017–0096, 2019–0009, 2019–0101, 2020–0079).

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Infection and inflammation.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 2.23 MB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nam, B., Lee, W., Sarkar, S. et al. In vivo detection of hydrogen sulfide in the brain of live mouse: application in neuroinflammation models. Eur J Nucl Med Mol Imaging 49, 4073–4087 (2022). https://doi.org/10.1007/s00259-022-05854-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-022-05854-1

Keywords

Search

Navigation