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2015 ; 35
(7
): 1696-703
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64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid
Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy
#MMPMID25977567
Pedersen SF
; Sandholt BV
; Keller SH
; Hansen AE
; Clemmensen AE
; Sillesen H
; Højgaard L
; Ripa RS
; Kjær A
Arterioscler Thromb Vasc Biol
2015[Jul]; 35
(7
): 1696-703
PMID25977567
show ga
OBJECTIVE: A feature of vulnerable atherosclerotic plaques of the carotid artery
is high activity and abundance of lesion macrophages. There is consensus that
this is of importance for plaque vulnerability, which may lead to clinical
events, such as stroke and transient ischemic attack. We used positron emission
tomography (PET) and the novel PET ligand [(64)Cu]
[1,4,7,10-tetraazacyclododecane-N,N',N?,N?-tetraacetic
acid]-d-Phe1,Tyr3-octreotate ((64)Cu-DOTATATE) to specifically target macrophages
via the somatostatin receptor subtype-2 in vivo. APPROACH AND RESULTS: Ten
patients underwent simultaneous PET/MRI to measure (64)Cu-DOTATATE uptake in
carotid artery plaques before carotid endarterectomy. (64)Cu-DOTATATE uptake was
significantly higher in symptomatic plaque versus the contralateral carotid
artery (P<0.001). Subsequently, a total of 62 plaque segments were assessed for
gene expression of selected markers of plaque vulnerability using real-time
quantitative polymerase chain reaction. These results were compared with in vivo
(64)Cu-DOTATATE uptake calculated as the mean standardized uptake value.
Univariate analysis of real-time quantitative polymerase chain reaction and PET
showed that cluster of differentiation 163 (CD163) and CD68 gene expression
correlated significantly but weakly with mean standardized uptake value in scans
performed 85 minutes post injection (P<0.001 and P=0.015, respectively).
Subsequent multivariate analysis showed that CD163 correlated independently with
(64)Cu-DOTATATE uptake (P=0.031) whereas CD68 did not contribute significantly to
the final model. CONCLUSIONS: The novel PET tracer (64)Cu-DOTATATE accumulates in
atherosclerotic plaques of the carotid artery. CD163 gene expression correlated
independently with (64)Cu-DOTATATE uptake measured by real-time quantitative
polymerase chain reaction in the final multivariate model, indicating that
(64)Cu-DOTATATE PET is detecting alternatively activated macrophages. This
association could potentially improve noninvasive identification and
characterization of vulnerable plaques.