PET/CT Imaging of Unstable Carotid Plaque with ⁶⁸Ga-Labeled Somatostatin Receptor Ligand

Abstract

68 Ga-labeled somatostatin receptor ligand PET imaging has recently been shown in preclinical and early human studies to have a potential role in the evaluation of vulnerable arterial plaques. We prospectively evaluated carotid plaque 68 Ga-DOTATATE uptake in patients with recent carotid events, assessed inter-and intraobserver variability of such measurements, and explored the mechanism of any plaque DOTATATE activity with immunohistochemistry in resected specimens. Methods: Twenty consecutively consenting patients with recent symptomatic carotid events (transient ischemic attack, stroke, or amaurosis fugax), due for carotid endarterectomy, were prospectively recruited. 68 Ga-DOTATATE PET/CT of the neck was performed before surgery. 68 Ga-DOTATATE uptake was measured by drawing regions of interest along the carotid plaques and contralateral plaques/carotid arteries by an experienced radionuclide radiologist and radiographer. Two PET quantification methods with inter-and intraobserver variability were assessed. Resected carotid plaques were retrieved for somatostatin receptor subtype-2 (sst2) immunohistochemical staining. Results: The median time delay between research PET and surgery was 2 d. SUVs and target-to-background ratios for the symptomatic plaques and the asymptomatic contralateral carotid arteries/plaques showed no significant difference (n 5 19, P . 0.10), regardless of quantification method. The intraclass correlation coefficient was greater than 0.8 in all measures of carotid artery/plaque uptake (SUV) and greater than 0.6 in almost all measures of target-to-background ratio. None of the excised plaques was shown to contain cells (macrophages, lymphocytes, vessel-associated cells) expressing sst2 on their cell membrane. Conclusion: 68 Ga-DOTATATE activity on PET in recently symptomatic carotid plaques is not significantly different from contralateral carotids/plaques. Any activity seen on PET is not shown to be from specific sst2 receptor-mediated uptake in vitro. It is therefore unlikely that sst2 PET/CT imaging will have a role in the detection and characterization of symptomatic carotid plaques. At herosclerosis is a leading cause of mortality and morbidity.There is the concept that although atherosclerotic plaques may contribute to symptoms by luminal stenosis, it is the disruption of unstable plaques that leads to catastrophic events, including stroke and myocardial infarction. Termed vulnerable plaques, these unstable plaques are believed to have characteristic features such as inflammatory cell infiltration, lipid cores, and fibrous caps (1,2).Measuring the degree of luminal stenosis was the mainstay of assessment and directed management decisions until recently (3-5). Recognition of this method's limitation has driven the use of biomarkers, such as fractional flow reserve, in coronary disease and exploration of functional imaging to noninvasively identify vulnerable plaques (6,7).Radionuclide imaging has the advantageous capability of directly probing molecular mechanisms in vivo using radi...

Molecular Imaging of Inflammation in Ischemic Heart Disease

“…68 Ga-DOTATATE uptake also correlated with high risk plaque features determined by CT. Coronary 68 Ga-DOTATATE was interpretable in all patients unlike 18 F-FDG PET, which could not be interpreted in 27 (64%) patients due to high myocardial background signal. These findings are in direct contrast to the negative study reported by Wan, et al 43 showing that 68 Ga-DOTATATE activity did not differ between symptomatic and contralateral plaques from patients who suffered transient ischemic attacks and were scheduled for carotid endarterectomy. The authors suggest that the lack of difference may be due to the imaging characteristics of 68 Ga-DOTATATE, which may be less sensitive to subtle differences in uptake than other tracers like 64 Cu-DOTATATE.…”

Imaging inflammation in atherosclerotic plaques, targeting SST2 with [111In]In-DOTA-JR11

“…[21][22][23] It is hypothesized that antagonistic ligands such as DOTA-JR11 have more binding sites on the receptor than agonistic ligands such as DOTA-TATE. 31 Although the exact mechanism for this difference in uptake remains to be elucidated, the growing amount of studies using SST 2 -mediated imaging in atherosclerosis [13][14][15][16][17][18][19] indicate DOTA-JR11 as an interesting candidate for further studies.…”

“…A number of studies have reported on the use of SST 2 for inflammation-based imaging of atherosclerosis. [13][14][15][16][17][18][19] Moreover, Tarkin Various radioligands, based on SST 2 agonists, for SST 2 -targeted imaging and therapy have been developed and used over the past 20 years for detection and treatment of SST 2 -expressing tumors. 21 More recently, a new generation of radioligands based on SST 2 antagonists has been developed and described, showing more favorable pharmacokinetics and higher tumor uptake than agonists like DOTATATE.…”

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach

“…Similarly, the mean [ 99m Tc]Tc-Demotate 2 uptake was also highest in the fibrous cap atheroma segments and also significantly higher compared with the fibrocalcific phenotype in line with the immunohistochemistry. Notwithstanding, to make a distinction in specific atherosclerotic plaque phenotype and the identification of vulnerable plaque characteristics remains a challenge based on the current radiotracers used in the clinic [13,32,33]. For example, clinical studies have reported difficulty in differentiating symptomatic carotid vessels compared with the contralateral asymptomatic diseased side where there is a high degree of disease present in the contralateral carotid vessel [13].…”

“…Notwithstanding, there are conflicting results reported for this radiotracer. For example, comparing symptomatic culprit vessels to the contralateral vessels in the carotid vasculature can result in little to no differences in terms of uptake levels [13,14]. The detection of 'culprit' inflamed vessels is partially impeded by the paucity of information linking radiotracer uptake with respect to the specific plaque phenotype.…”