Dataset Information

Toward molecular imaging of the free fatty acid receptor 1.

ABSTRACT:

Aims

Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling.

Methods

In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([³H]AZ1, [³H]AZ2 and [³H]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma.

Results

[³H]AZ1 showed improved specificity to FFAR1, with decreased off-target binding compared to [³H]AZ2 and [³H]TAK-875, while retaining high affinity in the nanomolar range. FFAR1 density in human islets was approximately 50% higher than in exocrine tissue.

Conclusions

AZ1 is a suitable lead compound for PET labeling for molecular imaging of FFAR1 in humans, due to high affinity and reduced off-target binding.

SUBMITTER: Hellstrom-Lindahl E

PROVIDER: S-EPMC5486603 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

Toward molecular imaging of the free fatty acid receptor 1.

Hellström-Lindahl Ewa E Åberg Ola O Ericsson Cecilia C O'Mahony Gavin G Johnström Peter P Skrtic Stanko S Eriksson Olof O

Acta diabetologica 20170413 7

<h4>Aims</h4>Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling.<h4>Methods</h4>In order to identify ...[more]

PMID: 28409274

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Dataset Information

Toward molecular imaging of the free fatty acid receptor 1.

Aims

Methods

Results

Conclusions

Publications

Toward molecular imaging of the free fatty acid receptor 1.

Similar Datasets

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