A Standardized Method for In Vivo Mouse Pancreas Imaging and Semiquantitative β Cell Mass Measurement by Dual Isotope SPECT
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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.
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.
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.
[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.
Key wordsExendin l-phenylalanine Dual isotope SPECT Beta cell mass Pancreas imaging
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.
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