scholarly journals PET Imaging of Crossed Cerebellar Diaschisis after Long-Term Cerebral Ischemia in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Ana Joya ◽  
Daniel Padro ◽  
Vanessa Gómez-Vallejo ◽  
Sandra Plaza-García ◽  
Jordi Llop ◽  
...  

Crossed cerebellar diaschisis (CCD) is a decrease of regional blood flow and metabolism in the cerebellar hemisphere contralateral to the injured brain hemisphere as a common consequence of stroke. Despite CCD has been detected in patients with stroke using neuroimaging modalities, the evaluation of this phenomenon in rodent models of cerebral ischemia has been scarcely evaluated so far. Here, we report the in vivo evaluation of CCD after long-term cerebral ischemia in rats using positron emission tomography (PET) imaging with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Imaging studies were combined with neurological evaluation to assess functional recovery. In the ischemic territory, imaging studies showed a significant decrease in glucose metabolism followed by a progressive recovery later on. Conversely, the cerebellum showed a contralateral hypometabolism from days 7 to 14 after reperfusion. Neurological behavior showed major impaired outcome at day 1 after ischemia followed by a significant recovery of the sensorimotor function from days 7 to 28 after experimental stroke. Taken together, these results suggest that the degree of CCD after cerebral ischemia might be predictive of neurological recovery.

2009 ◽  
Vol 30 (1) ◽  
pp. 230-241 ◽  
Author(s):  
Abraham Martín ◽  
Raphaël Boisgard ◽  
Benoit Thézé ◽  
Nadja Van Camp ◽  
Bertrand Kuhnast ◽  
...  

Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [18F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. In vivo PET imaging showed significant increase in DPA ( N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. In vitro autoradiography confirmed these in vivo results. In vivo and in vitro [18F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [18F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.


2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Simone Maschauer ◽  
Olaf Prante

At the time when the highly efficient [18F]FDG synthesis was discovered by the use of the effective precursor 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (mannose triflate) for nucleophilic18F-substitution, the field of PET in nuclear medicine experienced a long-term boom. Thirty years later, various strategies for chemoselective18F-labeling of biomolecules have been developed, trying to keep up with the emerging field of radiopharmaceutical sciences. Among the new radiochemical strategies, chemoselective18F-fluoroglycosylation methods aim at the sweetening of pharmaceutical radiochemistry by providing a powerful and highly valuable tool for the design of18F-glycoconjugates with suitablein vivoproperties for PET imaging studies. This paper provides a short review (reflecting the literature not older than 8 years) on the different18F-fluoroglycosylation reactions that have been applied to the development of various18F-glycoconjugate tracers, including not only peptides, but also nonpeptidic tracers and high-molecular-weight proteins.


2018 ◽  
Vol 15 (13) ◽  
pp. 1267-1275 ◽  
Author(s):  
F.E. Reesink ◽  
D. Vállez García ◽  
C.A. Sánchez-Catasús ◽  
D.E. Peretti ◽  
A.T. Willemsen ◽  
...  

Background: We describe the phenomenon of crossed cerebellar diaschisis (CCD) in four subjects diagnosed with Alzheimer’s disease (AD) according to the National Institute on Aging - Alzheimer Association (NIA-AA) criteria, in combination with 18F-FDG PET and 11C-PiB PET imaging. Methods: 18F-FDG PET showed a pattern of cerebral metabolism with relative decrease most prominent in the frontal-parietal cortex of the left hemisphere and crossed hypometabolism of the right cerebellum. 11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer delivery (a surrogate of relative cerebral blood flow) in the left hemisphere. CCD is the phenomenon of unilateral cerebellar hypometabolism as a remote effect of supratentorial dysfunction of the brain in the contralateral hemisphere. The mechanism implies the involvement of the cortico-ponto-cerebellar fibers. The pathophysiology is thought to have a functional or reversible basis but can also reflect in secondary morphologic change. CCD is a well-recognized phenomenon, since the development of new imaging techniques, although scarcely described in neurodegenerative dementias. Results: To our knowledge this is the first report describing CCD in AD subjects with documentation of both 18F-FDG PET and 11C-PiB PET imaging. CCD in our subjects was explained on a functional basis due to neurodegenerative pathology in the left hemisphere. There was no structural lesion and the symmetric amyloid accumulation did not correspond with the unilateral metabolic impairment. Conclusion: This suggests that CCD might be caused by non-amyloid neurodegeneration. The pathophysiological mechanism, clinical relevance and therapeutic implications of CCD and the role of the cerebellum in AD need further investigation.


2018 ◽  
Vol 54 (82) ◽  
pp. 11538-11541 ◽  
Author(s):  
N. L. Fletcher ◽  
Z. H. Houston ◽  
J. D. Simpson ◽  
R. N. Veedu ◽  
K. J. Thurecht

We report a novel multifunctional hyperbranched polymer based on polyethylene glycol (PEG) as a nanomedicine platform that facilitates longitudinal and quantitative 89Zr-PET imaging, enhancing knowledge of nanomaterial biodistribution and pharmacokinetics/pharmacodynamics both in vivo and ex vivo.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eduardo Romero ◽  
Alfonso Martínez ◽  
Marta Oteo ◽  
Marta Ibañez ◽  
Mirentxu Santos ◽  
...  

AbstractRadionuclide generator systems can routinely provide radionuclides on demand such as 68Ga produced by a 68Ge/68Ga generator without the availability of an on-site accelerator or a research reactor. Thus, in this work nano-SnO2 was used to develop a new 68Ge/68Ga generator which was evaluated over a period of 17 months and 305 elution cycles. The elution yield was 91.1 ± 1.8% in the first 7 mL (1 M HCl as eluent) when the generator was new and then it decreased with time and use to 73.8 ± 1.9%. Around 80% of the elutable 68Ga activity was obtained in 1 mL and the 68Ge content in the eluate did not exceed 1 × 10–4% over the investigation period when it was eluted regularly. The described generator provided adequate results for radiolabelling of DOTA-TOC with direct use of eluate. In addition, [68Ga]Ga-DOTA-TOC was tested satisfactorily for in vivo tumor detection by microPET/CT imaging in a lung cancer mouse model.


2018 ◽  
Vol 61 (6) ◽  
pp. 2278-2291 ◽  
Author(s):  
Ran Cheng ◽  
Wakana Mori ◽  
Longle Ma ◽  
Mireille Alhouayek ◽  
Akiko Hatori ◽  
...  

2017 ◽  
Vol 37 (3) ◽  
pp. 1163-1178 ◽  
Author(s):  
Geraldine Pottier ◽  
Vanessa Gómez-Vallejo ◽  
Daniel Padro ◽  
Raphaël Boisgard ◽  
Frédéric Dollé ◽  
...  

Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using positron emission tomography (PET) imaging. In this work, we report the evaluation of the in vivo expression of CB2R with [11C]A-836339 PET after cerebral ischemia and in two rat models of neuroinflammation, first by intrastriatal LPS and then by AMPA injection. PET images and in vitro autoradiography showed a lack of specific [11C]A-836339 uptake in these animal models demonstrating the limitation of this radiotracer to image CB2 receptor under neuroinflammatory conditions. Further, using immunohistochemistry, the CB2 receptor displayed a modest expression increase after cerebral ischemia, LPS and AMPA models. Finally, [18F]DPA-714-PET and immunohistochemistry demonstrated decreased neuroinflammation by a selective CB2R agonist, JWH133. Taken together, these findings suggest that [11C]A-836339 is not a suitable radiotracer to monitor in vivo CB2R expression by using PET imaging. Future studies will have to investigate alternative radiotracers that could provide an accurate binding to CB2 receptors following brain inflammation.


2010 ◽  
Vol 31 (2) ◽  
pp. 757-766 ◽  
Author(s):  
Gina Ziegler ◽  
Dorette Freyer ◽  
Denise Harhausen ◽  
Uldus Khojasteh ◽  
Wilfried Nietfeld ◽  
...  

Reduced infarct volume in TLR2-knockout mice compared with C57Bl/6 wild-type mice has recently been shown in experimental stroke and confirmed in this study. We now also show a significant decrease of CD11b-positive cell counts and decreased neuronal death in the ischemic hemispheres of TLR2-deficient mice compared with C57Bl/6wt mice 2 days after transient focal cerebral ischemia. To examine the potential benefit of intravascular TLR2 inhibition, C57Bl/6wt mice were treated intraarterially with TLR2-blocking anti-TLR2 antibody (clone T2.5) after 45 minutes of cerebral ischemia and compared with control antibody (isotype) treated wild-type mice. Whereas T2.5-treated mice had no reduction in infarct volumes at 48 hours after reperfusion, they did have decreased numbers of CD11b-positive inflammatory cells and decreased neuronal death compared with isotype-treated control mice. Comparison of the isotype antibody treatment to control (saline) treatment showed no effects on infarct volumes or neuronal survival. However, mice treated with the control isotype antibody had increased numbers of CD11b-positive inflammatory cells compared with saline-treated animals. Thus, antibody treatment itself (i.e., control isotype antibody, but potentially of any antibody) may have adverse effects and limit therapeutic benefit of anti-TLR2-antibody therapy. We conclude that TLR2 mediates leukocyte and microglial infiltration and neuronal death, which can be attenuated by TLR2 inhibition. The TLR2 inhibition in vivo improves neuronal survival and may represent a future stroke therapy.


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