| Exendin-4-based radiopharmaceuticals for glucagonlike peptide-1 receptor PET/CT and SPECT/CT. | |
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MedLine Citation:
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PMID: 20595511 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Strong overexpression of glucagonlike peptide-1 (GLP-1) receptors in human insulinoma provides an attractive target for imaging. The first clinical trials demonstrated that GLP-1 receptor SPECT/CT using [Lys(40)(Ahx [6-aminohexanoic acid]-DOTA-(111)In)NH(2)]-exendin-4 can localize hardly detectable insulinomas. However, [Lys(40)(Ahx-DOTA-(111)In)NH(2)]-exendin-4 imaging has drawbacks related to the use of (111)In in that it is costly and carries a relatively high radiation burden for the patient. The aim of this study was the preclinical evaluation of [Lys(40)(Ahx-DOTA-(68)Ga)NH(2)]-exendin-4 for PET/CT and [Lys(40)(Ahx-hydrazinonicotinamide [HYNIC]-(99m)Tc)NH(2)]-exendin-4 for SPECT/CT. METHODS: Internalization, biodistribution, dosimetry, and imaging studies were performed in the Rip1Tag2 mouse model of pancreatic beta-cell carcinogenesis and compared with our gold standard [Lys(40)(Ahx-DOTA-(111)In)NH(2)]-exendin-4. Poly-glutamic acid and Gelofusine, a gelatin-based plasma expander, were used for renal uptake reduction studies. RESULTS: The tumor uptake of [Lys(40)(Ahx-DOTA-(68)Ga)NH(2)]-exendin-4 was 205 +/- 59 percentage injected activity per gram of tissue at 4 h. Other GLP-1 receptor-positive organs showed more than 4.8 times lower radioactivity uptake. [Lys(40)(Ahx-HYNIC-(99m)Tc/ethylenediaminediacetic acid [EDDA])NH(2)]-exendin-4, compared with its (111)In- and (68)Ga-labeled sister compounds, showed significantly less tumor and organ uptake. The significantly lower tumor and organ uptake of [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)]-exendin-4 did not result in inferior tumor-to-organ ratios or reduced image quality. All radiopeptides tested showed a high tumor-to-background ratio, resulting in the visualization of small tumors (maximum diameter between 1.0 and 3.2 mm) by SPECT and PET. The only exception was the kidneys, which also showed high uptake. This uptake could be reduced by 49%-78% using poly-glutamic acid, Gelofusine, or a combination of the 2. The estimated effective radiation dose was 3.7 muSv/MBq for [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)]-exendin-4, which was 8 times less than that for [Lys(40)(Ahx-DOTA-(68)Ga)NH(2)]-exendin-4 and 43 times less than that for [Lys(40)(Ahx-DOTA-(111)In)NH(2)]-exendin-4. CONCLUSION: These promising pharmacokinetic and imaging data show that [Lys(40)(Ahx-DOTA-(68)Ga)NH(2)]-exendin-4 and [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)]-exendin-4 are suitable candidates for clinical GLP-1 receptor imaging studies. |
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Authors:
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Damian Wild; Andreas Wicki; Rosalba Mansi; Martin Béhé; Boris Keil; Peter Bernhardt; Gerhard Christofori; Peter J Ell; Helmut R Mäcke |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of nuclear medicine : official publication, Society of Nuclear Medicine Volume: 51 ISSN: 1535-5667 ISO Abbreviation: J. Nucl. Med. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-02 Completed Date: 2010-07-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217410 Medline TA: J Nucl Med Country: United States |
Other Details:
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Languages: eng Pagination: 1059-67 Citation Subset: IM |
Affiliation:
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Clinic and Institute of Nuclear Medicine, University Hospital Basel, Basel, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Dose-Response Relationship, Radiation Female Gallium Radioisotopes / diagnostic use Indicators and Reagents Indium Radioisotopes / diagnostic use Isotope Labeling Kidney / metabolism, radionuclide imaging Male Mice Mice, Transgenic Peptides / chemistry, diagnostic use* Positron-Emission Tomography Radiopharmaceuticals / chemistry, diagnostic use* Receptors, Glucagon / metabolism* Technetium Compounds / diagnostic use Tissue Distribution Tomography, Emission-Computed Tomography, Emission-Computed, Single-Photon Venoms / chemistry, diagnostic use* |
| Chemical | |
Reg. No./Substance:
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0/Gallium Radioisotopes; 0/Indicators and Reagents; 0/Indium Radioisotopes; 0/Peptides; 0/Radiopharmaceuticals; 0/Receptors, Glucagon; 0/Technetium Compounds; 0/Venoms; 0/glucagon-like peptide receptor; 141732-76-5/exenatide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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