Skip to main content
Top
Published in: EJNMMI Research 1/2015

Open Access 01-12-2015 | Preliminary research

SPECT imaging of glioma with radioiodinated CLINDE: evidence from a mouse GL26 glioma model

Authors: Stergios Tsartsalis, Noé Dumas, Benjamin B Tournier, Tien Pham, Marcelle Moulin-Sallanon, Marie-Claude Grégoire, Yves Charnay, Philippe Millet

Published in: EJNMMI Research | Issue 1/2015

Login to get access

Abstract

Background

Recent research has demonstrated the potential of 18-kDa translocator protein (TSPO) to serve as a target for nuclear imaging of gliomas. The aim of this study was to evaluate SPECT imaging of GL26 mouse glioma using radioiodinated CLINDE, a TSPO-specific tracer.

Methods

GL26 cells, previously transfected with an enhanced green fluorescent protein (EGFP)-expressing lentivirus, were stereotactically implanted in the striatum of C57/Bl6 mice. At 4 weeks post-injection, dynamic SPECT scans with [123I]CLINDE were performed. A displacement study assessed specificity of tracer binding. SPECT images were compared to results of autoradiography, fluorescence microscopy, in situ nucleic acid hybridization, histology, and immunohistochemistry. Western blotting was performed to verify TSPO production by the tumor.

Results

Specific uptake of tracer by the tumor is observed with a high signal-to-noise ratio. Tracer uptake by the tumor is indeed 3.26 ± 0.32 times higher than that of the contralateral striatum, and 78% of the activity is displaceable by unlabeled CLINDE. Finally, TSPO is abundantly expressed by the GL26 cells.

Conclusions

The present study demonstrates the feasibility of [123I]CLINDE SPECT in translational studies and underlines its potential for clinical glioma SPECT imaging.
Literature
2.
go back to reference Winkeler A, Boisgard R, Awde AR, Dubois A, Theze B, Zheng J, et al. The translocator protein ligand [(1)(8)F]DPA-714 images glioma and activated microglia in vivo. Eur J Nucl Med Mol Imaging. 2012;39(5):811–23.CrossRefPubMedCentralPubMed Winkeler A, Boisgard R, Awde AR, Dubois A, Theze B, Zheng J, et al. The translocator protein ligand [(1)(8)F]DPA-714 images glioma and activated microglia in vivo. Eur J Nucl Med Mol Imaging. 2012;39(5):811–23.CrossRefPubMedCentralPubMed
3.
go back to reference Tang D, Hight MR, McKinley ET, Fu A, Buck JR, Smith RA, et al. Quantitative preclinical imaging of TSPO expression in glioma using N, N-diethyl-2-(2-(4-(2–18 F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimi din-3-yl)acetamide. J Nucl Med. 2012;53(2):287–94.CrossRefPubMedCentralPubMed Tang D, Hight MR, McKinley ET, Fu A, Buck JR, Smith RA, et al. Quantitative preclinical imaging of TSPO expression in glioma using N, N-diethyl-2-(2-(4-(2–18 F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimi din-3-yl)acetamide. J Nucl Med. 2012;53(2):287–94.CrossRefPubMedCentralPubMed
4.
go back to reference Su Z, Herholz K, Gerhard A, Roncaroli F, Du Plessis D, Jackson A, et al. [(1)(1)C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging. 2013;40(9):1406–19.CrossRefPubMedCentralPubMed Su Z, Herholz K, Gerhard A, Roncaroli F, Du Plessis D, Jackson A, et al. [(1)(1)C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging. 2013;40(9):1406–19.CrossRefPubMedCentralPubMed
5.
go back to reference Mattner F, Bandin DL, Staykova M, Berghofer P, Gregoire MC, Ballantyne P, et al. Evaluation of [(1)(2)(3)I]-CLINDE as a potent SPECT radiotracer to assess the degree of astroglia activation in cuprizone-induced neuroinflammation. Eur J Nucl Med Mol Imaging. 2011;38(8):1516–28.CrossRefPubMed Mattner F, Bandin DL, Staykova M, Berghofer P, Gregoire MC, Ballantyne P, et al. Evaluation of [(1)(2)(3)I]-CLINDE as a potent SPECT radiotracer to assess the degree of astroglia activation in cuprizone-induced neuroinflammation. Eur J Nucl Med Mol Imaging. 2011;38(8):1516–28.CrossRefPubMed
6.
go back to reference Mattner F, Mardon K, Katsifis A. Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS). Eur J Nucl Med Mol Imaging. 2008;35(4):779–89.CrossRefPubMed Mattner F, Mardon K, Katsifis A. Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS). Eur J Nucl Med Mol Imaging. 2008;35(4):779–89.CrossRefPubMed
8.
go back to reference Mattner F, Katsifis A, Staykova M, Ballantyne P, Willenborg DO. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis. Eur J Nucl Med Mol Imaging. 2005;32(5):557–63.CrossRefPubMed Mattner F, Katsifis A, Staykova M, Ballantyne P, Willenborg DO. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis. Eur J Nucl Med Mol Imaging. 2005;32(5):557–63.CrossRefPubMed
9.
go back to reference Schiffer WK, Mirrione MM, Biegon A, Alexoff DL, Patel V, Dewey SL. Serial microPET measures of the metabolic reaction to a microdialysis probe implant. J Neurosci Methods. 2006;155(2):272–84.CrossRefPubMed Schiffer WK, Mirrione MM, Biegon A, Alexoff DL, Patel V, Dewey SL. Serial microPET measures of the metabolic reaction to a microdialysis probe implant. J Neurosci Methods. 2006;155(2):272–84.CrossRefPubMed
10.
go back to reference Charnay Y, Imhof A, Vallet PG, Hakkoum D, Lathuiliere A, Poku N, et al. Clusterin expression during fetal and postnatal CNS development in mouse. Neuroscience. 2008;155(3):714–24.CrossRefPubMed Charnay Y, Imhof A, Vallet PG, Hakkoum D, Lathuiliere A, Poku N, et al. Clusterin expression during fetal and postnatal CNS development in mouse. Neuroscience. 2008;155(3):714–24.CrossRefPubMed
11.
go back to reference Imhof A, Charnay Y, Vallet PG, Aronow B, Kovari E, French LE, et al. Sustained astrocytic clusterin expression improves remodeling after brain ischemia. Neurobiol Dis. 2006;22(2):274–83.CrossRefPubMed Imhof A, Charnay Y, Vallet PG, Aronow B, Kovari E, French LE, et al. Sustained astrocytic clusterin expression improves remodeling after brain ischemia. Neurobiol Dis. 2006;22(2):274–83.CrossRefPubMed
12.
13.
go back to reference Batarseh A, Papadopoulos V. Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol Cell Endocrinol. 2010;327(1–2):1–12.CrossRefPubMedCentralPubMed Batarseh A, Papadopoulos V. Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol Cell Endocrinol. 2010;327(1–2):1–12.CrossRefPubMedCentralPubMed
14.
go back to reference Buck JR, McKinley ET, Hight MR, Fu A, Tang D, Smith RA, et al. Quantitative, preclinical PET of translocator protein expression in glioma using 18 F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline. J Nucl Med. 2011;52(1):107–14.CrossRefPubMedCentralPubMed Buck JR, McKinley ET, Hight MR, Fu A, Tang D, Smith RA, et al. Quantitative, preclinical PET of translocator protein expression in glioma using 18 F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline. J Nucl Med. 2011;52(1):107–14.CrossRefPubMedCentralPubMed
15.
go back to reference Shah AH, Snelling B, Bregy A, Patel PR, Tememe D, Bhatia R, et al. Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality? J Neurooncol. 2013;112(2):141–52.CrossRefPubMed Shah AH, Snelling B, Bregy A, Patel PR, Tememe D, Bhatia R, et al. Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality? J Neurooncol. 2013;112(2):141–52.CrossRefPubMed
16.
go back to reference Zhang H, Ma L, Wu C, Xu B. Performance of SPECT in the differential diagnosis of glioma recurrence from radiation necrosis. J Clin Neurosci. 2015;22(2):229–37.CrossRefPubMed Zhang H, Ma L, Wu C, Xu B. Performance of SPECT in the differential diagnosis of glioma recurrence from radiation necrosis. J Clin Neurosci. 2015;22(2):229–37.CrossRefPubMed
17.
go back to reference Awde AR, Boisgard R, Theze B, Dubois A, Zheng J, Dolle F, et al. The translocator protein radioligand 18 F-DPA-714 monitors antitumor effect of erufosine in a rat 9 L intracranial glioma model. J Nucl Med. 2013;54(12):2125–31.CrossRefPubMed Awde AR, Boisgard R, Theze B, Dubois A, Zheng J, Dolle F, et al. The translocator protein radioligand 18 F-DPA-714 monitors antitumor effect of erufosine in a rat 9 L intracranial glioma model. J Nucl Med. 2013;54(12):2125–31.CrossRefPubMed
18.
go back to reference Su Z, Gerhard A, Hinz R, Coope DJ, Thompson G, Karabatsou K, et al. In vivo imaging of translocator protein expression in low-grade gliomas by positron emission tomography. Glasgow, UK: British Neuro-Oncology Society Annual Conference; 2010. Su Z, Gerhard A, Hinz R, Coope DJ, Thompson G, Karabatsou K, et al. In vivo imaging of translocator protein expression in low-grade gliomas by positron emission tomography. Glasgow, UK: British Neuro-Oncology Society Annual Conference; 2010.
19.
go back to reference Meikle SR, Kench P, Kassiou M, Banati RB. Small animal SPECT and its place in the matrix of molecular imaging technologies. Phys Med Biol. 2005;50(22):R45–61.CrossRefPubMed Meikle SR, Kench P, Kassiou M, Banati RB. Small animal SPECT and its place in the matrix of molecular imaging technologies. Phys Med Biol. 2005;50(22):R45–61.CrossRefPubMed
Metadata
Title
SPECT imaging of glioma with radioiodinated CLINDE: evidence from a mouse GL26 glioma model
Authors
Stergios Tsartsalis
Noé Dumas
Benjamin B Tournier
Tien Pham
Marcelle Moulin-Sallanon
Marie-Claude Grégoire
Yves Charnay
Philippe Millet
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-015-0092-4

Other articles of this Issue 1/2015

EJNMMI Research 1/2015 Go to the issue