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Utility of (18) F-FDG and (11)C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation.

English SJ, Diaz JA, Shao X, Gordon D, Bevard M, Su G, Henke PK, Rogers VE, Upchurch GR, Piert M - EJNMMI Res (2014)

Bottom Line: The utility of (18) F-FDG and (11)C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed.CD68 and translocator protein (TSPO) immunohistochemistry (IHC), as well as TSPO gene expression assays, were performed for validation.These results support further investigation of (18) F-FDG and (11)C-PBR28 in the noninvasive assessment of human AAA development.

View Article: PubMed Central - PubMed

Affiliation: Conrad Jobst Vascular Research Laboratories, University of Michigan Health System, Ann Arbor, MI, 48109, USA, seanengl@med.umich.edu.

ABSTRACT

Background: The utility of (18) F-FDG and (11)C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed.

Methods: Utilizing the porcine pancreatic elastase (PPE) perfusion model, abdominal aortas of male Sprague-Dawley rats were infused with active PPE (APPE, AAA; N = 24) or heat-inactivated PPE (IPPE, controls; N = 16). Aortic diameter increases were monitored by ultrasound (US). Three, 7, and 14 days after induction, APPE and IPPE rats were imaged using (18) F-FDG microPET (approximately 37 MBq IV) and compared with (18) F-FDG autoradiography (approximately 185 MBq IV) performed at day 14. A subset of APPE (N = 5) and IPPE (N = 6) animals were imaged with both (11)C-PBR28 (approximately 19 MBq IV) and subsequent (18) F-FDG (approximately 37 MBq IV) microPET on the same day 14 days post PPE exposure. In addition, autoradiography of the retroperitoneal torso was performed after (11)C-PBR28 (approximately 1,480 MBq IV) or (18) F-FDG (approximately 185 MBq IV) administration at 14 days post PPE exposure. Aortic wall-to-muscle ratios (AMRs) were determined for microPET and autoradiography. CD68 and translocator protein (TSPO) immunohistochemistry (IHC), as well as TSPO gene expression assays, were performed for validation.

Results: Mean 3 (p = 0.009), 7 (p < 0.0001) and 14 (p < 0.0001) days aortic diameter increases were significantly greater for APPE AAAs compared to IPPE controls. No significant differences in (18) F-FDG AMR were determined at days 3 and 7 post PPE exposure; however, at day 14, the mean (18) F-FDG AMR was significantly elevated in APPE AAAs compared to IPPE controls on both microPET (p = 0.0002) and autoradiography (p = 0.02). Similarly, mean (11)C-PBR28 AMR was significantly increased at day 14 in APPE AAAs compared to IPPE controls on both microPET (p = 0.04) and autoradiography (p = 0.02). For APPE AAAs, inhomogeneously increased (18) F-FDG and (11)C-PBR28 uptake was noted preferentially at the anterolateral aspect of the AAA. Compared to controls, APPE AAAs demonstrated significantly increased macrophage cell counts by CD68 IHC (p = 0.001) as well as increased TSPO staining (p = 0.004). Mean TSPO gene expression for APPE AAAs was also significantly elevated compared to IPPE controls (p = 0.0002).

Conclusion: Rat AAA wall inflammation can be visualized using (18) F-FDG and (11)C-PBR28 microPET revealing regional differences of radiotracer uptake on microPET and autoradiography. These results support further investigation of (18) F-FDG and (11)C-PBR28 in the noninvasive assessment of human AAA development.

No MeSH data available.


Related in: MedlinePlus

18 F-FDG and 11C-PBR28 microPET. Representative coronal microPET images of an IPPE control animal (A-D) and an APPE abdominal aortic aneurysm (AAA) animal (E-H). Early (A, E) and late (B, F) phase 18 F-FDG scans, with respective early (C, G) and late (D, H) phase 11C-PBR images are shown. Sequential imaging allows for the identification of the aortic wall (red arrows), kidneys (black arrow), and ureteral activity (white arrow).
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Fig2: 18 F-FDG and 11C-PBR28 microPET. Representative coronal microPET images of an IPPE control animal (A-D) and an APPE abdominal aortic aneurysm (AAA) animal (E-H). Early (A, E) and late (B, F) phase 18 F-FDG scans, with respective early (C, G) and late (D, H) phase 11C-PBR images are shown. Sequential imaging allows for the identification of the aortic wall (red arrows), kidneys (black arrow), and ureteral activity (white arrow).

Mentions: Figure 2 displays representative 18 F-FDG and 11C-PBR28 microPET images. Image analysis was complicated, as aortic wall uptake was generally lower than the radioactivity in bowel in both 18 F-FDG and 11C-PBR28 scans. However, the blood pool activity seen on early phase imaging (0 to 90 s. p.i.) revealed the location of the abdominal aorta and AAAs. On late phase images, AAAs were always visually identifiable on both 11C-PBR28 and 18 F-FDG microPET data. However, a clear trend favoring one of the two tracers for visualization of AAAs was not observed.Figure 2


Utility of (18) F-FDG and (11)C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation.

English SJ, Diaz JA, Shao X, Gordon D, Bevard M, Su G, Henke PK, Rogers VE, Upchurch GR, Piert M - EJNMMI Res (2014)

18 F-FDG and 11C-PBR28 microPET. Representative coronal microPET images of an IPPE control animal (A-D) and an APPE abdominal aortic aneurysm (AAA) animal (E-H). Early (A, E) and late (B, F) phase 18 F-FDG scans, with respective early (C, G) and late (D, H) phase 11C-PBR images are shown. Sequential imaging allows for the identification of the aortic wall (red arrows), kidneys (black arrow), and ureteral activity (white arrow).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593011&req=5

Fig2: 18 F-FDG and 11C-PBR28 microPET. Representative coronal microPET images of an IPPE control animal (A-D) and an APPE abdominal aortic aneurysm (AAA) animal (E-H). Early (A, E) and late (B, F) phase 18 F-FDG scans, with respective early (C, G) and late (D, H) phase 11C-PBR images are shown. Sequential imaging allows for the identification of the aortic wall (red arrows), kidneys (black arrow), and ureteral activity (white arrow).
Mentions: Figure 2 displays representative 18 F-FDG and 11C-PBR28 microPET images. Image analysis was complicated, as aortic wall uptake was generally lower than the radioactivity in bowel in both 18 F-FDG and 11C-PBR28 scans. However, the blood pool activity seen on early phase imaging (0 to 90 s. p.i.) revealed the location of the abdominal aorta and AAAs. On late phase images, AAAs were always visually identifiable on both 11C-PBR28 and 18 F-FDG microPET data. However, a clear trend favoring one of the two tracers for visualization of AAAs was not observed.Figure 2

Bottom Line: The utility of (18) F-FDG and (11)C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed.CD68 and translocator protein (TSPO) immunohistochemistry (IHC), as well as TSPO gene expression assays, were performed for validation.These results support further investigation of (18) F-FDG and (11)C-PBR28 in the noninvasive assessment of human AAA development.

View Article: PubMed Central - PubMed

Affiliation: Conrad Jobst Vascular Research Laboratories, University of Michigan Health System, Ann Arbor, MI, 48109, USA, seanengl@med.umich.edu.

ABSTRACT

Background: The utility of (18) F-FDG and (11)C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed.

Methods: Utilizing the porcine pancreatic elastase (PPE) perfusion model, abdominal aortas of male Sprague-Dawley rats were infused with active PPE (APPE, AAA; N = 24) or heat-inactivated PPE (IPPE, controls; N = 16). Aortic diameter increases were monitored by ultrasound (US). Three, 7, and 14 days after induction, APPE and IPPE rats were imaged using (18) F-FDG microPET (approximately 37 MBq IV) and compared with (18) F-FDG autoradiography (approximately 185 MBq IV) performed at day 14. A subset of APPE (N = 5) and IPPE (N = 6) animals were imaged with both (11)C-PBR28 (approximately 19 MBq IV) and subsequent (18) F-FDG (approximately 37 MBq IV) microPET on the same day 14 days post PPE exposure. In addition, autoradiography of the retroperitoneal torso was performed after (11)C-PBR28 (approximately 1,480 MBq IV) or (18) F-FDG (approximately 185 MBq IV) administration at 14 days post PPE exposure. Aortic wall-to-muscle ratios (AMRs) were determined for microPET and autoradiography. CD68 and translocator protein (TSPO) immunohistochemistry (IHC), as well as TSPO gene expression assays, were performed for validation.

Results: Mean 3 (p = 0.009), 7 (p < 0.0001) and 14 (p < 0.0001) days aortic diameter increases were significantly greater for APPE AAAs compared to IPPE controls. No significant differences in (18) F-FDG AMR were determined at days 3 and 7 post PPE exposure; however, at day 14, the mean (18) F-FDG AMR was significantly elevated in APPE AAAs compared to IPPE controls on both microPET (p = 0.0002) and autoradiography (p = 0.02). Similarly, mean (11)C-PBR28 AMR was significantly increased at day 14 in APPE AAAs compared to IPPE controls on both microPET (p = 0.04) and autoradiography (p = 0.02). For APPE AAAs, inhomogeneously increased (18) F-FDG and (11)C-PBR28 uptake was noted preferentially at the anterolateral aspect of the AAA. Compared to controls, APPE AAAs demonstrated significantly increased macrophage cell counts by CD68 IHC (p = 0.001) as well as increased TSPO staining (p = 0.004). Mean TSPO gene expression for APPE AAAs was also significantly elevated compared to IPPE controls (p = 0.0002).

Conclusion: Rat AAA wall inflammation can be visualized using (18) F-FDG and (11)C-PBR28 microPET revealing regional differences of radiotracer uptake on microPET and autoradiography. These results support further investigation of (18) F-FDG and (11)C-PBR28 in the noninvasive assessment of human AAA development.

No MeSH data available.


Related in: MedlinePlus