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Updated: Dec 6, 2025
Longitudinal In Vivo Imaging and Quantification of Human Pancreatic Islet Grafting and Contributing Host Cells in the Anterior Eye Chamber
Published on: June 11, 2020
Beta Cell Imaging-From Pre-Clinical Validation to First in Man Testing
Stephane Demine1, Michael L Schulte2, Paul R Territo2,3
1Indiana Biosciences Research Institute, Indianapolis, IN 46202, USA.
Abstract:
There are presently no reliable ways to quantify human pancreatic beta cell mass (BCM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. Furthermore, the lack of beta cell imaging hampers the evaluation of the impact of new drugs aiming to prevent beta cell loss or to restore BCM in diabetes. We presently discuss the potential value of BCM determination as a cornerstone for individualized therapies in diabetes, describe the presently available probes for human BCM evaluation, and discuss our approach for the discovery of novel beta cell biomarkers, based on the determination of specific splice variants present in human beta cells. This has already led to the identification of DPP6 and FXYD2ga as two promising targets for human BCM imaging, and is followed by a discussion of potential safety issues, the role for radiochemistry in the improvement of BCM imaging, and concludes with an overview of the different steps from pre-clinical validation to a first-in-man trial for novel tracers.
Insights
Quantifying human pancreatic beta cell mass (BCM) in vivo is crucial for diabetes research and treatment. New biomarkers like DPP6 and FXYD2ga show promise for BCM imaging and personalized therapies.
Area of Science:
- Endocrinology
- Medical Imaging
- Molecular Biology
Background:
- Accurate quantification of human pancreatic beta cell mass (BCM) in vivo is currently unavailable.
- This limitation hinders understanding of diabetes progression and the efficacy of islet transplantation.
- The absence of beta cell imaging impedes the assessment of novel diabetes drugs targeting BCM.
Purpose of the Study:
- To highlight the significance of BCM determination for personalized diabetes therapies.
- To review existing probes for human BCM evaluation.
- To introduce a novel approach for discovering beta cell biomarkers using splice variants.
Main Methods:
- Investigated specific splice variants in human beta cells to identify novel biomarkers.
- Evaluated DPP6 and FXYD2ga as potential targets for human BCM imaging.
- Discussed radiochemistry's role in advancing BCM imaging techniques.
Main Results:
- Identified DPP6 and FXYD2ga as promising targets for human BCM imaging.
- Explored the potential of splice variants for beta cell biomarker discovery.
- Outlined the pathway from pre-clinical validation to human trials for new tracers.
Conclusions:
- Developing reliable in vivo methods for BCM quantification is essential for diabetes management.
- Novel biomarkers derived from splice variants offer new avenues for beta cell imaging.
- Advancements in radiochemistry and biomarker discovery pave the way for improved BCM imaging and personalized diabetes treatments.
