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Nucl Med Biol. 2014 Jul;41(6):471-6. doi: 10.1016/j.nucmedbio.2014.03.017. Epub 2014 Mar 29.

Pre-clinical evaluation of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 for imaging of insulinoma.

Author information

1
Preclinical PET Platform (PPP), Department of Medicinal Chemistry, Uppsala University, SE-751 83 Uppsala, Sweden. Electronic address: ramkumar.selvaraju@pet.medchem.uu.se.
2
Preclinical PET Platform (PPP), Department of Medicinal Chemistry, Uppsala University, SE-751 83 Uppsala, Sweden; Department of Radiology, Oncology and Radiation Sciences, Uppsala University, SE-751 85 Uppsala, Sweden; PET Centre, Centre for Medical Imaging, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
3
Preclinical PET Platform (PPP), Department of Medicinal Chemistry, Uppsala University, SE-751 83 Uppsala, Sweden.
4
Department of Radiology, Oncology and Radiation Sciences, Uppsala University, SE-751 85 Uppsala, Sweden; AstraZeneca R&D, SE-431 83 Mölndal, Sweden.
5
Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
6
Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
7
Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.

Abstract

INTRODUCTION:

Insulinoma is the most common form of pancreatic endocrine tumors responsible for hyperinsulinism in adults. These tumors overexpress glucagon like peptide-1 (GLP-1) receptor, and biologically stable GLP-1 analogs have therefore been proposed as potential imaging agents. Here, we evaluate the potential of a positron emission tomography (PET) tracer, [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4, for imaging and quantification of GLP-1 receptors (GLP-1R) in insulinoma.

METHODS:

[(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was evaluated for binding to GLP-1R by in vitro autoradiography binding studies in INS-1 tumor from xenografts. In vivo biodistribution was investigated in healthy control mice, INS-1 xenografted and PANC1 xenografted immunodeficient mice at two different doses of peptide: 2.5μg/kg (baseline) and 100μg/kg (block). In vivo imaging of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in xenografted mice was evaluated by small animal PET/CT using a direct comparison with the clinically established insulinoma marker [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP).

RESULTS:

GLP-1 receptor density could be quantified in INS-1 tumor biopsies. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 showed significant uptake (p≤0.05) in GLP1-R positive tissues such as INS-1 tumor, lungs and pancreas upon comparison between baseline and blocking studies. In vivo imaging showed concordant results with higher tumor-to-muscle ratio in INS-1 xenografted mice compared with [(11)C]5-HTP.

CONCLUSION:

[(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 has high affinity and specificity for GLP-1R expressed on insulinoma in vitro and in vivo.

KEYWORDS:

Glucagon like peptide-1 receptor (GLP-1R); Insulinoma; Positron emission tomography (PET); [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4

PMID:
24857864
DOI:
10.1016/j.nucmedbio.2014.03.017
[Indexed for MEDLINE]

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