TY - JOUR
T1 - Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [11C]PBR28 PET
AU - Shao, Xia
AU - Wang, Xueding
AU - English, Sean J.
AU - Desmond, Timothy
AU - Sherman, Phillip S.
AU - Quesada, Carole A.
AU - Piert, Morand R.
N1 - Funding Information:
Supported by the National Institutes of Health (NIH) under grant number R01 AR060350 and R01 AR055179.
PY - 2013/10
Y1 - 2013/10
N2 - Introduction: [11C] PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models. Methods: Acute inflammation was induced by local carrageenan injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [11C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak 11C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [11C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures. Results: LPS-stimulated macrophages displayed dose-dependent increased [11C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of carrageenan-treated paws was significantly increased compared to controls. Also, the [11C]PBR28 uptake ratio of carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [11C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips. Conclusions: Based on our initial data, [11C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving macrophage activation.
AB - Introduction: [11C] PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models. Methods: Acute inflammation was induced by local carrageenan injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [11C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak 11C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [11C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures. Results: LPS-stimulated macrophages displayed dose-dependent increased [11C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of carrageenan-treated paws was significantly increased compared to controls. Also, the [11C]PBR28 uptake ratio of carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [11C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips. Conclusions: Based on our initial data, [11C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving macrophage activation.
KW - Carrageenan-induced inflammation macrophages, RAW 264.7 cells
KW - Systemic adjuvant arthritis
KW - TSPO
KW - [C]PBR28
UR - http://www.scopus.com/inward/record.url?scp=84883553434&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2013.06.008
DO - 10.1016/j.nucmedbio.2013.06.008
M3 - Article
C2 - 23891203
AN - SCOPUS:84883553434
VL - 40
SP - 906
EP - 911
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
SN - 0969-8051
IS - 7
ER -