Investigating vulnerable atheroma using combined 18F-FDG PET/CT angiography of carotid plaque with immunohistochemical validation

Leon J. Menezes, Carl W. Kotze, Obi Agu, Toby Richards, Jocelyn Brookes, Vicky J. Goh, Manuel Rodriguez-Justo, Raymondo Endozo, Richard Harvey, Syed W. Yusuf, Peter J. Ell, Ashley M. Groves

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid 18F-FDG PET/CT angiography. Plaque 18F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. Results: The mean (±SD) surgically excised carotid plaque 18F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque 18F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ 5 0.47; P 5 0.031). There was an inverse relationship between plaque 18F-FDG metabolism and plaque percentage calcium composition on CT (ρ= -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ 5 20.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.

Original languageEnglish
Pages (from-to)1698-1703
Number of pages6
JournalJournal of Nuclear Medicine
Issue number11
Publication statusPublished - 1 Nov 2011
Externally publishedYes


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