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PET Imaging of GPR44 by Antagonist [C-11]MK-7246 in Pigs
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- Cheung, Pierre (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Zhang, Bo (author)
- Uppsala universitet,Translationell avbildning med PET,Science for Life Laboratory, SciLifeLab
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- Puuvuori, Emmi (author)
- Uppsala universitet,Translationell avbildning med PET,Science for Life Laboratory, SciLifeLab
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- (creator_code:org_t)
- 2021-04-16
- 2021
- English.
- In: Biomedicines. - : MDPI. - 2227-9059. ; 9:4
- Journal article (peer-reviewed)
Abstract
Subject headings
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- A validated imaging marker for beta-cell mass would improve understanding of diabetes etiology and enable new strategies in therapy development. We previously identified the membrane-spanning protein GPR44 as highly expressed and specific to the beta cells of the pancreas. The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [C-11]MK-7246 was evaluated in a pig model and in vitro cell lines. The [C-11]MK-7246 compound demonstrated mainly hepatobiliary excretion with a clearly defined pancreas, no spillover from adjacent tissues, and pancreatic binding similar in magnitude to the previously evaluated GPR44 radioligand [C-11]AZ12204657. The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [C-11]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- pancreas imaging
- diabetes
- biomarker
- PET
- PTGDR2
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- art (subject category)
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- Cheung, Pierre
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- Ye, Sofie
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- Korsgren, Olle
- Odell, Luke R.
- Eriksson, Jonas
- Eriksson, Olof
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