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The development of ...
The development of a GPR44 targeting radioligand [11C]AZ12204657 for in vivo assessment of beta cell mass.
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Jahan, Mahabuba (författare)
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Johnström, Peter (författare)
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- Selvaraju, Ramkumar (författare)
- Uppsala universitet,Plattformen för Preklinisk PET-MRI,Science for Life Laboratory, SciLifeLab
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Svedberg, Marie (författare)
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Winzell, Maria Sörhede (författare)
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Bernström, Jenny (författare)
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Kingston, Lee (författare)
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- Schou, Magnus (författare)
- Karolinska Institutet
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Jia, Zhisheng (författare)
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Skrtic, Stanko (författare)
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Johansson, Lars (författare)
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- Korsgren, Olle (författare)
- Uppsala universitet,Klinisk immunologi
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- Farde, Lars (författare)
- Karolinska Institutet
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- Halldin, Christer (författare)
- Karolinska Institutet
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- Eriksson, Olof (författare)
- Uppsala universitet,Theranostics
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(creator_code:org_t)
- 2018-12-27
- 2018
- Engelska.
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 8
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://ejnmmires.sp...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BACKGROUND: The G-protein-coupled receptor 44 (GPR44) is a beta cell-restricted target that may serve as a marker for beta cell mass (BCM) given the development of a suitable PET ligand.METHODS: The binding characteristics of the selected candidate, AZ12204657, at human GPR44 were determined using in vitro ligand binding assays. AZ12204657 was radiolabeled using 11C- or 3H-labeled methyl iodide ([11C/3H]CH3I) in one step, and the conversion of [11C/3H]CH3I to the radiolabeled product [11C/3H]AZ12204657 was quantitative. The specificity of radioligand binding to GPR44 and the selectivity for beta cells were evaluated by in vitro binding studies on pancreatic sections from human and non-human primates as well as on homogenates from endocrine and exocrine pancreatic compartments.RESULTS: The radiochemical purity of the resulting radioligand [11C]AZ12204657 was > 98%, with high molar activity (MA), 1351 ± 575 GBq/μmol (n = 18). The radiochemical purity of [3H]AZ12204657 was > 99% with MA of 2 GBq/μmol. Pancreatic binding of [11C/3H]AZ12204657 was co-localized with insulin-positive islets of Langerhans in non-diabetic individuals and individuals with type 2 diabetes (T2D). The binding of [11C]AZ12204657 to GPR44 was > 10 times higher in islet homogenates compared to exocrine homogenates. In human islets of Langerhans GPR44 was co-expressed with insulin, but not glucagon as assessed by co-staining and confocal microscopy.CONCLUSION: We radiolabeled [11C]AZ12204657, a potential PET radioligand for the beta cell-restricted protein GPR44. In vitro evaluation demonstrated that [3H]AZ12204657 and [11C]AZ12204657 selectively target pancreatic beta cells. [11C]AZ12204657 has promising properties as a marker for human BCM.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Beta cell imaging
- Beta cell mass
- Diabetes
- G-protein-coupled receptor 44 (GPR44)
- Islet imaging
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Jahan, Mahabuba
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Johnström, Peter
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Selvaraju, Ramku ...
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Svedberg, Marie
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Winzell, Maria S ...
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Bernström, Jenny
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visa fler...
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Kingston, Lee
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Schou, Magnus
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Jia, Zhisheng
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Skrtic, Stanko
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Johansson, Lars
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Korsgren, Olle
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Farde, Lars
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Halldin, Christe ...
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Eriksson, Olof
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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EJNMMI Research
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet