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Molecules. 2018 Aug 21;23(9). pii: E2100. doi: 10.3390/molecules23092100.

Imaging of Human Insulin Secreting Cells with Gd-DOTA-P88, a Paramagnetic Contrast Agent Targeting the Beta Cell Biomarker FXYD2γa.

Author information

1
ULB-Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Route de Lennik, Brussels 808-CP618, 1070 Brussels, Belgium. stephane.demine@ulb.ac.be.
2
ULB-Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Route de Lennik, Brussels 808-CP618, 1070 Brussels, Belgium. a.balhuizen@gmail.com.
3
Laboratoire G-Time, Université Libre de Bruxelles (ULB), Av. F.D. Roosevelt 50 CP 160/02, 1050 Brussels, Belgium. vdebaill@ulb.ac.be.
4
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands. Lieke.Claessens-Joosten@radboudumc.nl.
5
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000 Mons, Belgium. fereau.maite@gmail.com.
6
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000 Mons, Belgium. satyamurthy.chilla@gmail.com.
7
ULB-Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Route de Lennik, Brussels 808-CP618, 1070 Brussels, Belgium. Isabelle.Millard@ulb.ac.be.
8
INSERM U1016, Université Paris-Descartes, Institut Cochin, 75014 Paris, France. raphael.scharfmann@inserm.fr.
9
Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles (ULB) and University of Mons, 12 Rue des Professeurs Jeener et Brachet, 6041 Charleroi-Gosselies, Belgium. Dominique.Egrise@erasme.ulb.ac.be.
10
Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles (ULB) and University of Mons, 12 Rue des Professeurs Jeener et Brachet, 6041 Charleroi-Gosselies, Belgium. sgoldman@ulb.ac.be.
11
Department of Clinical and Experimental Medicine, and University Hospital, University of Pisa, 56100 Pisa, Italy. piero.marchetti@med.unipi.it.
12
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands. martin.gotthardt@radboudumc.nl.
13
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000 Mons, Belgium. Sophie.LAURENT@umons.ac.be.
14
Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles (ULB) and University of Mons, 12 Rue des Professeurs Jeener et Brachet, 6041 Charleroi-Gosselies, Belgium. Sophie.LAURENT@umons.ac.be.
15
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000 Mons, Belgium. Carmen.BURTEA@umons.ac.be.
16
ULB-Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Route de Lennik, Brussels 808-CP618, 1070 Brussels, Belgium. deizirik@ulb.ac.be.

Abstract

Non-invasive imaging and quantification of human beta cell mass remains a major challenge. We performed pre-clinical in vivo validation of a peptide previously discovered by our group, namely, P88 that targets a beta cell specific biomarker, FXYD2γa. We conjugated P88 with DOTA and then complexed it with GdCl₃ to obtain the MRI (magnetic resonance imaging) contrast agent (CA) Gd-DOTA-P88. A scrambled peptide was used as a negative control CA, namely Gd-DOTA-Scramble. The CAs were injected in immunodeficient mice implanted with EndoC-βH1 cells, a human beta cell line that expresses FXYD2γa similarly to primary human beta cells. The xenograft-bearing mice were analyzed by MRI. At the end, the mice were euthanized and the CA biodistribution was evaluated on the excised tissues by measuring the Gd concentration with inductively coupled plasma mass spectrometry (ICP-MS). The MRI and biodistribution studies indicated that Gd-DOTA-P88 accumulates in EndoC-βH1 xenografts above the level observed in the background tissue, and that its uptake is significantly higher than that observed for Gd-DOTA-Scramble. In addition, the Gd-DOTA-P88 showed good xenograft-to-muscle and xenograft-to-liver uptake ratios, two potential sites of human islets transplantation. The CA shows good potential for future use to non-invasively image implanted human beta cells.

KEYWORDS:

MRI; Type 1 diabetes; Type 2 diabetes; beta cell imaging; non-invasive imaging; pancreatic beta cell; paramagnetic contrast agent; peptide-based imaging

PMID:
30134599
PMCID:
PMC6225257
DOI:
10.3390/molecules23092100
[Indexed for MEDLINE]
Free PMC Article

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