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A Standardized Method for In Vivo Mouse Pancreas Imaging and Semiquantitative β Cell Mass Measurement by Dual Isotope SPECT

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Abstract

Purpose

In order to evaluate future β cell tracers in vivo, we aimed to develop a standardized in vivo method allowing semiquantitative measurement of a prospective β cell tracer within the pancreas.

Procedures

2-[123I]Iodo-l-phenylalanine ([123I]IPA) and [Lys40([111In]DTPA)]exendin-3 ([111In]Ex3) pancreatic uptake and biodistribution were evaluated using SPECT, autoradiography, and an ex vivo biodistribution study in a controlled unilaterally nephrectomized mouse β cell depletion model. Semiquantitative measurement of the imaging results was performed using [123I]IPA to delineate the pancreas and [111In]Ex3 as a β cell tracer.

Results

The uptake of [123I]IPA was highest in the pancreas. Aside from the kidneys, the uptake of [111In]Ex3 was highest in the pancreas and lungs. Autoradiography showed only uptake of [111In]Ex3 in insulin-expressing cells. Semiquantitative measurement of [111In]Ex3 in the SPECT images based on the delineation of the pancreas with [123I]IPA showed a high correlation with the [111In]Ex3 uptake data of the pancreas obtained by dissection. A strong positive correlation was observed between the relative insulin positive area and the pancreas-to-blood ratios of [111In]Ex3 uptake as determined by counting with a gamma counter and the semiquantitative analysis of the SPECT images.

Conclusions

[123I]IPA is a promising tracer to delineate pancreatic tissue on SPECT images. It shows a high uptake in the pancreas as compared to other abdominal tissues. This study also demonstrates the feasibility and accuracy to measure the β cell mass in vivo in an animal model of diabetes.

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Acknowledgments

Our work was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013), project BetaImage, under grant agreement n° 222980. We thank William Rabiot, Emmy De Blay, and Chéraz Mehiri for technical support.

Conflict of Interest

The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Cell Differentiation Unit, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium

    Iris Mathijs & Luc Bouwens

  2. In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium

    Catarina Xavier, Cindy Peleman, Vicky Caveliers & Tony Lahoutte

  3. Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    Maarten Brom & Martin Gotthardt

  4. Department of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva 4, Switzerland

    Pedro L. Herrera

Authors
  1. Iris Mathijs
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  2. Catarina Xavier
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  3. Cindy Peleman
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  4. Vicky Caveliers
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  5. Maarten Brom
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  7. Pedro L. Herrera
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  8. Tony Lahoutte
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  9. Luc Bouwens
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Corresponding author

Correspondence to Luc Bouwens.

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Mathijs, I., Xavier, C., Peleman, C. et al. A Standardized Method for In Vivo Mouse Pancreas Imaging and Semiquantitative β Cell Mass Measurement by Dual Isotope SPECT. Mol Imaging Biol 17, 58–66 (2015). https://doi.org/10.1007/s11307-014-0771-y

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  • DOI: https://doi.org/10.1007/s11307-014-0771-y

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