Abstract | PURPOSE: METHODS: Targeting of insulinomas with [Lys(40)( DOTA)] exendin-3 labelled with either (111)In or (68)Ga was investigated in vitro using insulinoma tumour cells (INS-1). [Lys(40)((111)In- DTPA)] Exendin-3 was used as a reference in this study. In vivo targeting was investigated in BALB/c nude mice with subcutaneous INS-1 tumours. PET imaging was performed using a preclinical PET/CT scanner. RESULTS: In vitro exendin-3 specifically bound and was internalized by GLP-1R-positive cells. In BALB/c nude mice with subcutaneous INS-1 tumours a high uptake of [Lys(40)((111)In- DTPA)] exendin-3 in the tumour was observed (33.5 +/- 11.6%ID/g at 4 h after injection). Uptake was specific, as determined by coinjection of an excess of unlabelled [Lys(40)] exendin-3 (1.8 +/- 0.1%ID/g). The pancreas also exhibited high and specific uptake (11.3 +/- 1.0%ID/g). High uptake was also found in the kidneys (144 +/- 24%ID/g) and this uptake was not receptor-mediated. In this murine tumour model optimal targeting of the GLP-1R expressing tumour was obtained at exendin doses < or =0.1 microg. Remarkably, tumour uptake of (68)Ga-labelled [Lys(40)( DOTA)] exendin-3 was lower (8.9 +/- 3.1%ID/g) than tumour uptake of (111)In-labelled [Lys(40)( DTPA)] exendin-3 (25.4 +/- 7.2%ID/g). The subcutaneous tumours were clearly visualized by small-animal PET imaging after injection of 3 MBq of [Lys(40)((68)Ga- DOTA)] exendin-3. CONCLUSION:
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Authors | Maarten Brom, Wim J G Oyen, Lieke Joosten, Martin Gotthardt, Otto C Boerman |
Journal | European journal of nuclear medicine and molecular imaging
(Eur J Nucl Med Mol Imaging)
Vol. 37
Issue 7
Pg. 1345-55
(Jul 2010)
ISSN: 1619-7089 [Electronic] Germany |
PMID | 20111963
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Gallium Radioisotopes
- Heterocyclic Compounds, 1-Ring
- Peptides
- exendin 3
- 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
- Pentetic Acid
- Lysine
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Topics |
- Amino Acid Sequence
- Animals
- Biological Transport
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Female
- Gallium Radioisotopes
- Heterocyclic Compounds, 1-Ring
(chemistry)
- Inhibitory Concentration 50
- Injections
- Insulinoma
(diagnostic imaging, metabolism)
- Kinetics
- Lysine
(chemistry)
- Mice
- Molecular Sequence Data
- Pentetic Acid
(chemistry)
- Peptides
(chemistry, metabolism, pharmacokinetics)
- Positron-Emission Tomography
(methods)
- Rats
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