Evaluation of [18F]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-03-18

AUTHORS

Saeka Shimochi, Thomas Keller, Ella Kujala, Joonas Khabbal, Johan Rajander, Eliisa Löyttyniemi, Olof Solin, Pirjo Nuutila, Shigehiko Kanaya, Emrah Yatkin, Tove J. Grönroos, Hidehiro Iida

ABSTRACT

PurposeRecent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide ([18F]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats.ProceduresNeuropathic pain was induced in rats (n = 20) by PSNL, and pain sensation tests were conducted before surgery and 3 and 7 days post-injury. On day 7, in vivo PET imaging and ex vivo autoradiography were performed using [18F]F-DPA or [11C]PK11195. Ex vivo biodistribution and PET imaging of the removed spinal cord were carried out with [18F]F-DPA. Sham-operated and PK11195-pretreated animals were also examined.ResultsMechanical allodynia was confirmed in the PSNL rats from day 3 through day 7. Ex vivo autoradiography showed a higher lesion-to-background uptake with [18F]F-DPA compared with [11C]PK11195. Ex vivo PET imaging of the removed spinal cord showed [18F]F-DPA accumulation in the inflammation site, which was immunohistochemically confirmed to coincide with microglia activation. Pretreatment with PK11195 eliminated the uptake. The SUV values of in vivo [18F]F-DPA and [11C]PK11195 PET were not significantly increased in the lesion compared with the reference region, and were fivefold higher than the values obtained from the ex vivo data. Ex vivo biodistribution revealed a twofold higher [18F]F-DPA uptake in the vertebral body compared to that seen in the bone from the skull.Conclusions[18F]F-DPA aided visualization of the spinal cord inflammation site in PSNL rats on ex vivo autoradiography and was superior to [11C]PK11195. In vivo [18F]F-DPA PET did not allow for visualization of tracer accumulation even using a high-spatial-resolution PET scanner. The main reason for this result was due to insufficient SUVs in the spinal cord region as compared with the background noise, in addition to a spillover from the vertebral body. More... »

PAGES

641-650

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-022-01713-5

DOI

http://dx.doi.org/10.1007/s11307-022-01713-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1146380384

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35303205


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24 schema:description Abstract PurposeRecent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide ([18F]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats.ProceduresNeuropathic pain was induced in rats (n = 20) by PSNL, and pain sensation tests were conducted before surgery and 3 and 7 days post-injury. On day 7, in vivo PET imaging and ex vivo autoradiography were performed using [18F]F-DPA or [11C]PK11195. Ex vivo biodistribution and PET imaging of the removed spinal cord were carried out with [18F]F-DPA. Sham-operated and PK11195-pretreated animals were also examined.ResultsMechanical allodynia was confirmed in the PSNL rats from day 3 through day 7. Ex vivo autoradiography showed a higher lesion-to-background uptake with [18F]F-DPA compared with [11C]PK11195. Ex vivo PET imaging of the removed spinal cord showed [18F]F-DPA accumulation in the inflammation site, which was immunohistochemically confirmed to coincide with microglia activation. Pretreatment with PK11195 eliminated the uptake. The SUV values of in vivo [18F]F-DPA and [11C]PK11195 PET were not significantly increased in the lesion compared with the reference region, and were fivefold higher than the values obtained from the ex vivo data. Ex vivo biodistribution revealed a twofold higher [18F]F-DPA uptake in the vertebral body compared to that seen in the bone from the skull.Conclusions[18F]F-DPA aided visualization of the spinal cord inflammation site in PSNL rats on ex vivo autoradiography and was superior to [11C]PK11195. In vivo [18F]F-DPA PET did not allow for visualization of tracer accumulation even using a high-spatial-resolution PET scanner. The main reason for this result was due to insufficient SUVs in the spinal cord region as compared with the background noise, in addition to a spillover from the vertebral body.
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30 schema:keywords DPA uptake
31 N-diethyl
32 PET
33 PET imaging
34 PET scanner
35 PK11195
36 PSNL rats
37 PurposeRecent studies
38 SUV
39 SUV values
40 accumulation
41 activation
42 addition
43 allodynia
44 animals
45 autoradiography
46 background noise
47 background uptake
48 biodistribution
49 body
50 bone
51 cord
52 cord regions
53 data
54 day 3
55 day 7
56 days
57 dpa
58 emission tomography scanner
59 evaluation
60 ex
61 ex vivo autoradiography
62 ex vivo data
63 feasibility
64 glia
65 high lesions
66 high spatial resolution
67 imaging
68 inflammation sites
69 lesions
70 ligation
71 main reason
72 microglia activation
73 microglial activation
74 model
75 nerve ligation
76 neuropathic pain
77 noise
78 pain
79 partial sciatic nerve ligation
80 positron emission tomography scanner
81 pretreatment
82 pyrimidin-3
83 rat model
84 rats
85 reasons
86 reference region
87 region
88 resolution
89 results
90 scanner
91 sciatic nerve ligation
92 sensation tests
93 sensitivity
94 sham
95 sites
96 skull
97 spatial resolution
98 spillovers
99 spinal cord
100 spinal cord microglial activation
101 spinal cord regions
102 spinal glia
103 study
104 surgery
105 test
106 tomography scanner
107 tracer accumulation
108 twofold
109 uptake
110 values
111 vertebral body
112 visualization
113 vivo
114 vivo PET imaging
115 vivo autoradiography
116 vivo data
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