title: In vivo monitoring of the antiangiogenic effect of neurotensin receptor-mediated radiotherapy by small-animal positron emission tomography: a pilot study.
abstract: The neurotensin receptor (NTS1) has emerged as an interesting target for molecular imaging and radiotherapy of NTS-positive tumors due to the overexpression in a range of tumors. The aim of this study was to develop a 177Lu-labeled NTS1 radioligand, its application for radiotherapy in a preclinical model and the imaging of therapy success by small-animal positron emission tomography (µPET) using [68Ga]DOTA-RGD as a specific tracer for imaging angiogenesis. The 177Lu-labeled peptide was subjected to studies on HT29-tumor-bearing nude mice in vivo, defining four groups of animals (single dose, two fractionated doses, four fractionated doses and sham-treated animals). Body weight and tumor diameters were determined three times per week. Up to day 28 after treatment, µPET studies were performed with [68Ga]DOTA-RGD. At days 7-10 after treatment with four fractionated doses of 11-14 MBq (each at days 0, 3, 6 and 10), the tumor growth was slightly decreased in comparison with untreated animals. Using a single high dose of 51 MBq, a significantly decreased tumor diameter of about 50% was observed with the beginning of treatment. Our preliminary PET imaging data suggested decreased tumor uptake values of [68Ga]DOTA-RGD in treated animals compared to controls at day 7 after treatment. This pilot study suggests that early PET imaging with [68Ga]DOTA-RGD in radiotherapy studies to monitor integrin expression could be a promising tool to predict therapy success in vivo. Further successive PET experiments are needed to confirm the significance and predictive value of RGD-PET for NTS-mediated radiotherapy.
authors.affiliation: Department of Nuclear Medicine, Laboratory of Molecular Imaging and Radiochemistry, Friedrich Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany. simone.maschauer@uk-erlangen.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Maschauer
authors.affiliation: Department of Nuclear Medicine, Laboratory of Molecular Imaging and Radiochemistry, Friedrich Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany. tina_ruckdeschel@gmx.de.
authors.forename: Tina
authors.initials: T
authors.lastname: Ruckdeschel
authors.affiliation: Department of Nuclear Medicine, Laboratory of Molecular Imaging and Radiochemistry, Friedrich Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany. philipp.tripal@uk-erlangen.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Tripal
authors.affiliation: Department of Nuclear Medicine, Innsbruck Medical University, Anichstr. 35, 6020 Innsbruck, Austria. roland.haubner@i-med.ac.at.
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.affiliation: Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstraße 19, 91052 Erlangen, Germany. rgen.einsiedel@fau.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Einsiedel
authors.affiliation: Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstraße 19, 91052 Erlangen, Germany. harald.huebner@fau.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Hübner
authors.affiliation: Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstraße 19, 91052 Erlangen, Germany. peter.gmeiner@fau.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
authors.affiliation: Department of Nuclear Medicine, Laboratory of Molecular Imaging and Radiochemistry, Friedrich Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany. torsten.kuwert@uk-erlangen.de.
authors.forename: Torsten
authors.initials: T
authors.lastname: Kuwert
authors.affiliation: Department of Nuclear Medicine, Laboratory of Molecular Imaging and Radiochemistry, Friedrich Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany. olaf.prante@uk-erlangen.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Prante
references.citation: Radiother Oncol. 2010 Sep;96(3):280-7
references.pmid: 20724013
references.citation: ChemMedChem. 2013 May;8(5):772-8
references.pmid: 23532897
references.citation: ACS Med Chem Lett. 2010 May 21;1(5):224-8
references.pmid: 24900199
references.citation: Bioorg Med Chem Lett. 2008 Mar 15;18(6):2013-8
references.pmid: 18276136
references.citation: J Biol Chem. 1973 Oct 10;248(19):6854-61
references.pmid: 4745447
references.citation: Bioorg Med Chem. 2008 Oct 15;16(20):9359-68
references.pmid: 18809332
references.citation: Eur J Nucl Med Mol Imaging. 2007 Nov;34(11):1804-14
references.pmid: 17594090
references.citation: Cancer Biother Radiopharm. 2007 Jun;22(3):374-81
references.pmid: 17651043
references.citation: Eur J Nucl Med Mol Imaging. 2008 Aug;35(8):1507-15
references.pmid: 18369617
references.citation: J Nucl Med. 2011 Jan;52(1):140-6
references.pmid: 21149494
references.citation: Front Endocrinol (Lausanne). 2013 Jan 17;3:184
references.pmid: 23335914
references.citation: J Pept Res. 2002 Feb;59(2):55-61
references.pmid: 11906607
references.citation: FEBS Lett. 1991 Oct 7;291(1):50-4
references.pmid: 1718779
references.citation: J Med Chem. 2004 Oct 21;47(22):5587-90
references.pmid: 15481995
references.citation: J Nucl Med. 2003 Oct;44(10):1649-54
references.pmid: 14530481
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: ACS Chem Biol. 2009 Jul 17;4(7):503-25
references.pmid: 19462983
references.citation: J Med Chem. 2011 Apr 28;54(8):2915-23
references.pmid: 21446649
references.citation: J Nucl Med. 2009 May;50 Suppl 1:1S-10S
references.pmid: 19380403
references.citation: Trends Pharmacol Sci. 1999 Jul;20(7):302-9
references.pmid: 10390649
references.citation: J Med Chem. 2000 Feb 24;43(4):756-62
references.pmid: 10691700
references.citation: Nucl Med Biol. 2006 May;33(4):495-503
references.pmid: 16720241
references.citation: Microvasc Res. 2014 Mar;92:1-9
references.pmid: 24215790
references.citation: Biochimie. 2011 Sep;93(9):1369-78
references.pmid: 21605619
references.citation: ChemMedChem. 2013 Jan;8(1):75-81
references.pmid: 23097347
references.citation: Bioconjug Chem. 2011 Jul 20;22(7):1374-85
references.pmid: 21662976
references.citation: Int J Pept Protein Res. 1994 Sep;44(3):233-8
references.pmid: 7822099
references.citation: Eur J Nucl Med Mol Imaging. 2010 Aug;37 Suppl 1:S86-103
references.pmid: 20559632
references.citation: Nucl Med Biol. 2006 May;33(4):505-12
references.pmid: 16720242
references.citation: Gut. 1998 Apr;42(4):546-50
references.pmid: 9616318
references.citation: J Med Chem. 2009 Apr 9;52(7):1803-13
references.pmid: 19290594
references.citation: Eur J Nucl Med Mol Imaging. 2009 Jan;36(1):37-47
references.pmid: 18690434
references.citation: Regul Pept. 2000 Sep 25;93(1-3):125-36
references.pmid: 11033059
references.citation: Eur J Nucl Med Mol Imaging. 2003 Aug;30(8):1134-9
references.pmid: 12768332
references.citation: Chemistry. 2006 Aug 16;12(24):6315-22
references.pmid: 16729342
references.citation: J Nucl Med. 2011 Mar;52(3):424-30
references.pmid: 21321268
references.citation: Angew Chem Int Ed Engl. 2010;49(5):976-9
references.pmid: 20029856
references.citation: J Med Chem. 2006 Jul 27;49(15):4767-76
references.pmid: 16854083
references.citation: Radiat Res. 1997 Nov;148(5):435-42
references.pmid: 9355868
references.citation: Mol Pharmacol. 1980 Jul;18(1):11-9
references.pmid: 6251356
references.citation: Biochem Pharmacol. 1973 Dec 1;22(23):3099-108
references.pmid: 4202581