Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas.
Beta cell mass
Endocrine-to-exocrine ratio
Human pancreas
Radiolabelled exendin
SPECT/CT imaging
Journal
EJNMMI research
ISSN: 2191-219X
Titre abrégé: EJNMMI Res
Pays: Germany
ID NLM: 101560946
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
received:
15
12
2023
accepted:
03
10
2024
medline:
15
10
2024
pubmed:
15
10
2024
entrez:
15
10
2024
Statut:
epublish
Résumé
Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass. ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496 . gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508 .
Sections du résumé
BACKGROUND
BACKGROUND
Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with
CONCLUSION
CONCLUSIONS
Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496 .
CLINICALTRIALS
RESULTS
gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508 .
Identifiants
pubmed: 39405026
doi: 10.1186/s13550-024-01159-6
pii: 10.1186/s13550-024-01159-6
doi:
Banques de données
ClinicalTrials.gov
['NCT03889496', 'NCT04733508']
Types de publication
Journal Article
Langues
eng
Pagination
96Subventions
Organisme : JDRF
ID : 2-SRA-2014-266-M-B
Pays : United States
Organisme : Diabetes Fonds
ID : 2015-81-1845
Organisme : FP7 Ideas: European Research Council
ID : 602812
Organisme : Innovative Medicines Initiative
ID : 115797
Organisme : Innovative Medicines Initiative
ID : 948268
Organisme : ZonMw
ID : 95105008
Pays : Netherlands
Informations de copyright
© 2024. The Author(s).
Références
Krogvold L, Edwin B, Buanes T, Ludvigsson J, Korsgren O, Hyoty H, et al. Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study. Diabetologia. 2014;57:841–3. https://doi.org/10.1007/s00125-013-3155-y .
doi: 10.1007/s00125-013-3155-y
pubmed: 24429579
Eriksson O, Laughlin M, Brom M, Nuutila P, Roden M, Hwa A, et al. In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use. Diabetologia. 2016;59:1340–9. https://doi.org/10.1007/s00125-016-3959-7 .
doi: 10.1007/s00125-016-3959-7
pubmed: 27094935
Brom M, Joosten L, Frielink C, Peeters H, Bos D, van Zanten M, et al. Validation of (111)In-Exendin SPECT for the determination of the beta-cell Mass in BioBreeding Diabetes-Prone rats. Diabetes. 2018;67:2012–8. https://doi.org/10.2337/db17-1312 .
doi: 10.2337/db17-1312
pubmed: 30045920
Joosten L, Brom M, Peeters H, Bos D, Himpe E, Bouwens L, et al. Measuring the pancreatic beta cell Mass in Vivo with exendin SPECT during hyperglycemia and severe Insulitis. Mol Pharm. 2019;16:4024–30. https://doi.org/10.1021/acs.molpharmaceut.9b00728 .
doi: 10.1021/acs.molpharmaceut.9b00728
pubmed: 31345042
Tornehave D, Kristensen P, Romer J, Knudsen LB, Heller RS. Expression of the GLP-1 receptor in mouse, rat, and human pancreas. J Histochem Cytochem. 2008;56:841–51. https://doi.org/10.1369/jhc.2008.951319 .
doi: 10.1369/jhc.2008.951319
pubmed: 18541709
pmcid: 2516959
Brom M, Woliner-van der Weg W, Joosten L, Frielink C, Bouckenooghe T, Rijken P, et al. Non-invasive quantification of the beta cell mass by SPECT with (1)(1)(1)In-labelled exendin. Diabetologia. 2014;57:950–9. https://doi.org/10.1007/s00125-014-3166-3 .
doi: 10.1007/s00125-014-3166-3
pubmed: 24488022
Brom M, Joosten L, Frielink C, Boerman O, Gotthardt M. (111)In-exendin uptake in the pancreas correlates with the beta-cell mass and not with the alpha-cell mass. Diabetes. 2015;64:1324–8. https://doi.org/10.2337/db14-1212 .
doi: 10.2337/db14-1212
pubmed: 25409700
Jansen TJP, Brom M, Boss M, Buitinga M, Tack CJ, van Meijel LA, et al. Importance of beta cell mass for glycaemic control in people with type 1 diabetes. Diabetologia. 2022;1–9. https://doi.org/10.1007/s00125-022-05830-2 .
Oram RA, Sims EK, Evans-Molina C. Beta cells in type 1 diabetes: mass and function; sleeping or dead? Diabetologia. 2019;62:567–77. https://doi.org/10.1007/s00125-019-4822-4 .
doi: 10.1007/s00125-019-4822-4
pubmed: 30767048
pmcid: 6688846
Yu MG, Keenan HA, Shah HS, Frodsham SG, Pober D, He Z, et al. Residual beta cell function and monogenic variants in long-duration type 1 diabetes patients. J Clin Invest. 2019;129:3252–63. https://doi.org/10.1172/JCI127397 .
doi: 10.1172/JCI127397
pubmed: 31264968
pmcid: 6668678
Keenan HA, Sun JK, Levine J, Doria A, Aiello LP, Eisenbarth G, et al. Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes. 2010;59:2846–53. https://doi.org/10.2337/db10-0676 .
doi: 10.2337/db10-0676
pubmed: 20699420
pmcid: 2963543
Klinke DJ 2. Extent of beta cell destruction is important but insufficient to predict the onset of type 1 diabetes mellitus. PLoS ONE. 2008;3:e1374. https://doi.org/10.1371/journal.pone.0001374 .
Jansen TJP, Buitinga M, Boss M, Nijhoff MF, Brom M, de Galan BE, et al. Monitoring beta cell survival after intrahepatic islet transplantation using dynamic exendin PET imaging: a proof-of-concept study in individuals with type 1 diabetes. Diabetes. 2023. https://doi.org/10.2337/db22-0884 .
doi: 10.2337/db22-0884
pubmed: 37068261
Ekholm R, Ericson LE, Lundquist I. Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography. Diabetologia. 1971;7:339–48. https://doi.org/10.1007/BF01219468 .
doi: 10.1007/BF01219468
pubmed: 4943990
Schafer MK, Hartwig NR, Kalmbach N, Klietz M, Anlauf M, Eiden LE, Weihe E. Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models. Diabetologia. 2013;56:1047–56. https://doi.org/10.1007/s00125-013-2847-7 .
doi: 10.1007/s00125-013-2847-7
pubmed: 23404442
pmcid: 3955760
Saisho Y, Harris PE, Butler AE, Galasso R, Gurlo T, Rizza RA, Butler PC. Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas. J Mol Histol. 2008;39:543–51. https://doi.org/10.1007/s10735-008-9195-9 .
doi: 10.1007/s10735-008-9195-9
pubmed: 18791800
pmcid: 2566800
Eriksson J, Roy T, Sawadjoon S, Bachmann K, Skold C, Larhed M, et al. Synthesis and preclinical evaluation of the CRTH2 antagonist [(11)C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass. Nucl Med Biol. 2019;71:1–10. https://doi.org/10.1016/j.nucmedbio.2019.04.002 .
doi: 10.1016/j.nucmedbio.2019.04.002
pubmed: 31082767
Eriksson O, Johnstrom P, Cselenyi Z, Jahan M, Selvaraju RK, Jensen-Waern M, et al. In vivo visualization of beta-cells by targeting of GPR44. Diabetes. 2018;67:182–92. https://doi.org/10.2337/db17-0764 .
doi: 10.2337/db17-0764
pubmed: 29208633
Jahan M, Johnstrom P, Selvaraju RK, Svedberg M, Winzell MS, Bernstrom J, et al. The development of a GPR44 targeting radioligand [(11)C]AZ12204657 for in vivo assessment of beta cell mass. EJNMMI Res. 2018;8:113. https://doi.org/10.1186/s13550-018-0465-6 .
doi: 10.1186/s13550-018-0465-6
pubmed: 30588560
pmcid: 6306373
Eriksson O, Korsgren O, Selvaraju RK, Mollaret M, de Boysson Y, Chimienti F, Altai M. Pancreatic imaging using an antibody fragment targeting the zinc transporter type 8: a direct comparison with radio-iodinated Exendin-4. Acta Diabetol. 2018;55:49–57. https://doi.org/10.1007/s00592-017-1059-x .
doi: 10.1007/s00592-017-1059-x
pubmed: 29064047
Farino ZJ, Morgenstern TJ, Maffei A, Quick M, De Solis AJ, Wiriyasermkul P, et al. New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion. Mol Psychiatry. 2020;25:2070–85. https://doi.org/10.1038/s41380-018-0344-6 .
doi: 10.1038/s41380-018-0344-6
pubmed: 30626912
Bini J, Sanchez-Rangel E, Gallezot JD, Naganawa M, Nabulsi N, Lim K, et al. PET imaging of pancreatic dopamine D2 and D3 receptor density with (11)C-(+)-PHNO in type 1 diabetes. Journal of nuclear medicine: official publication. Soc Nuclear Med. 2020;61:570–6. https://doi.org/10.2967/jnumed.119.234013 .
doi: 10.2967/jnumed.119.234013
Boss M, Kusmartseva I, Woliner- van der Weg W, Joosten L, Brom M, Béhe M, et al. 111In-exendin spect imaging suggests presence of residual beta cells in patients with longstanding type 1 diabetes. Diabetologia. 2020;43(Abstract). https://doi.org/10.1007/s00125-020-05221-5 .
Willekens SM, Joosten L, Boerman OC, Balhuizen A, Eizirik DL, Gotthardt M, Brom M. Strain Differences Determine the Suitability of Animal Models for noninvasive in vivo Beta cell Mass determination with radiolabeled exendin. Mol Imaging Biol. 2016;18:705–14. https://doi.org/10.1007/s11307-016-0936-y .
doi: 10.1007/s11307-016-0936-y
pubmed: 26886298
pmcid: 5010585
Boss M, Buitinga M, Jansen TJ, Brom M, Visser EP, Gotthardt M. PET-based dosimetry of [(68)Ga]Ga-NODAGA-exendin-4 in humans, a tracer for beta cell imaging. J Nuclear Medicine: Official Publication Soc Nuclear Med. 2019. https://doi.org/10.2967/jnumed.119.228627 .
doi: 10.2967/jnumed.119.228627
van der Kroon I, Woliner-van der Weg W, Brom M, Joosten L, Frielink C, Konijnenberg MW, et al. Whole organ and islet of Langerhans dosimetry for calculation of absorbed doses resulting from imaging with radiolabeled exendin. Sci Rep. 2017;7:39800. https://doi.org/10.1038/srep39800 .
doi: 10.1038/srep39800
pubmed: 28067253
pmcid: 5220322