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

Tsartsalis S, Dumas N, Tournier BB, Pham T, Moulin-Sallanon M, Grégoire MC, Charnay Y, Millet P - EJNMMI Res (2015)

Bottom Line: SPECT images were compared to results of autoradiography, fluorescence microscopy, in situ nucleic acid hybridization, histology, and immunohistochemistry.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.

View Article: PubMed Central - PubMed

Affiliation: Vulnerability Biomarkers Unit, Division of General Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Chemin du Petit-Bel-Air 2, CH1225 Geneva, Chêne-Bourg Switzerland ; Department of Psychiatry, University of Geneva, 1 rue Michel-Servet, CH1211 Geneva 4, Switzerland.

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 [(123)I]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 [(123)I]CLINDE SPECT in translational studies and underlines its potential for clinical glioma SPECT imaging.

No MeSH data available.


Related in: MedlinePlus

In vivoSPECT imaging, histology andex vivoautoradiography.In vivo SPECT image (summed frames between 50 and 80 min of scan), co-registered with a mouse brain MRI template, obtained from one mouse bearing the GL26 tumor in the coronal (A), sagittal (B), and axial (C) planes. VOIs corresponding to tumor and contralateral brain tissue are also depicted. (D)Ex vivo autoradiography of a corresponding brain section from the same mouse. Color scale refers to percentage of maximal activity in the image.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4385259&req=5

Fig1: In vivoSPECT imaging, histology andex vivoautoradiography.In vivo SPECT image (summed frames between 50 and 80 min of scan), co-registered with a mouse brain MRI template, obtained from one mouse bearing the GL26 tumor in the coronal (A), sagittal (B), and axial (C) planes. VOIs corresponding to tumor and contralateral brain tissue are also depicted. (D)Ex vivo autoradiography of a corresponding brain section from the same mouse. Color scale refers to percentage of maximal activity in the image.

Mentions: Figure 1A,B,C shows an in vivo SPECT image (averaged over frames corresponding to 50 to 80 min post-injection of tracer), co-registered to the mouse MRI template. A corresponding coronal brain section after ex vivo autoradiography is presented in Figure 1D. Figure 2 (left part) illustrates the tissue-activity curves (TACs) extracted from the dynamic images of seven mice using two circular VOIs manually delineated on the tumor as well as an equal size VOI on the contralateral striatum. A rapid tracer uptake is observed in the initial frames post-injection followed by washout that, for the contralateral VOI, is almost complete and rapid. Analysis of averaged image frames between 50 and 80 min post-injection across different experimental subjects demonstrated that the tumor side (mean SUV 1.04 ± 0.22) presents a level of radioactivity 3.26 ± 0.32 times higher than that of the contralateral side (mean SUV 0.32 ± 0.08, p < 0.001). TACs of the dynamic scan presented in Figure 2 (right part) also depict the result of a displacement experiment in which 10 mg/kg of unlabeled compound were injected at 82 min post-injection. Radioactivity kinetic pattern in the tumor VOI reveals that about 78% of the radioactivity is displaceable.Figure 1


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

Tsartsalis S, Dumas N, Tournier BB, Pham T, Moulin-Sallanon M, Grégoire MC, Charnay Y, Millet P - EJNMMI Res (2015)

In vivoSPECT imaging, histology andex vivoautoradiography.In vivo SPECT image (summed frames between 50 and 80 min of scan), co-registered with a mouse brain MRI template, obtained from one mouse bearing the GL26 tumor in the coronal (A), sagittal (B), and axial (C) planes. VOIs corresponding to tumor and contralateral brain tissue are also depicted. (D)Ex vivo autoradiography of a corresponding brain section from the same mouse. Color scale refers to percentage of maximal activity in the image.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385259&req=5

Fig1: In vivoSPECT imaging, histology andex vivoautoradiography.In vivo SPECT image (summed frames between 50 and 80 min of scan), co-registered with a mouse brain MRI template, obtained from one mouse bearing the GL26 tumor in the coronal (A), sagittal (B), and axial (C) planes. VOIs corresponding to tumor and contralateral brain tissue are also depicted. (D)Ex vivo autoradiography of a corresponding brain section from the same mouse. Color scale refers to percentage of maximal activity in the image.
Mentions: Figure 1A,B,C shows an in vivo SPECT image (averaged over frames corresponding to 50 to 80 min post-injection of tracer), co-registered to the mouse MRI template. A corresponding coronal brain section after ex vivo autoradiography is presented in Figure 1D. Figure 2 (left part) illustrates the tissue-activity curves (TACs) extracted from the dynamic images of seven mice using two circular VOIs manually delineated on the tumor as well as an equal size VOI on the contralateral striatum. A rapid tracer uptake is observed in the initial frames post-injection followed by washout that, for the contralateral VOI, is almost complete and rapid. Analysis of averaged image frames between 50 and 80 min post-injection across different experimental subjects demonstrated that the tumor side (mean SUV 1.04 ± 0.22) presents a level of radioactivity 3.26 ± 0.32 times higher than that of the contralateral side (mean SUV 0.32 ± 0.08, p < 0.001). TACs of the dynamic scan presented in Figure 2 (right part) also depict the result of a displacement experiment in which 10 mg/kg of unlabeled compound were injected at 82 min post-injection. Radioactivity kinetic pattern in the tumor VOI reveals that about 78% of the radioactivity is displaceable.Figure 1

Bottom Line: SPECT images were compared to results of autoradiography, fluorescence microscopy, in situ nucleic acid hybridization, histology, and immunohistochemistry.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.

View Article: PubMed Central - PubMed

Affiliation: Vulnerability Biomarkers Unit, Division of General Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Chemin du Petit-Bel-Air 2, CH1225 Geneva, Chêne-Bourg Switzerland ; Department of Psychiatry, University of Geneva, 1 rue Michel-Servet, CH1211 Geneva 4, Switzerland.

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 [(123)I]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 [(123)I]CLINDE SPECT in translational studies and underlines its potential for clinical glioma SPECT imaging.

No MeSH data available.


Related in: MedlinePlus