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Session: Cardiovascular diseases
Session starts: Friday 25 January, 13:00
Presentation starts: 14:15
Room: Lecture room 558

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Hilary Barrett ()
Eric Meester ()
Monique Bernsen ()
Kim van der Heiden ()
Anton van der Steen ()
Marion de Jong ()
Frank Gijsen ()

Abstract:
The clinical application of nuclear imaging is a rapidly emerging diagnostic technique for atherosclerotic disease which holds prodigious promise to differentiate vulnerable symptomatic patients from the safe asymptomatic cohorts through the detection of molecular mechanisms linked to the disease manifestation. Specifically, inflammation is advocated as the key driver in the atherosclerotic disease progression and plays an instrumental role in causing life-threatening clinical complications. Recent advancements in non-invasive molecular single photon emission computed tomography (SPECT) imaging technology permit dual-radioisotope imaging. Thus, this study evaluates the potential of novel radiotracers targeting inflammatory cell types leukocytes and activated macrophages simultaneously in human diseased arteries. Human carotid plaque samples were obtained from eight endarterectomy patients in the Erasmus Medical Center, The Netherlands in a manner that conformed to the declaration of Helsinki and was approved by the hospital’s Ethical Research Committee. The plaques were sectioned into 2 mm segments, isolating a total of 23 segments including segments from each of the three anatomical regions of the carotid artery vessel (Internal ICA, bifurcation BIF and common CCA). The plaque slices were incubated in radioactive solution of (99mTc-Demotate + 111In-Danbirt) (radioactivity = 100MBq/nmol). Ultra-high resolution focused imaging high-energy (HE) VECTor collimators was used which has a <500um reconstructed resolution and sensitivity >2800cps/MBq (Vector 5, MiLabs Utrecht). Scans were reconstructed using the 0.2mm voxel size SROSEM (Similarity Regulated Ordered Subset Expectation Maximization). Simultaneous dual-energy windows were used for separated quantification of counts with the nuclear properties of are 99mTc [gamma photon peaks of 140 keV] and 111In [gamma photon peaks of 171, 245 keV]. The samples were further cryo-sectioned into 5um slices and were immunohistochemically stained to assess co-localization of LFA-1 and SSTR-2 positive cells in the plaque segments. This study develops an optimal dual-tracer protocol for imaging dual inflammation targets in human diseased arteries. Quantification of the radiotracer uptake (MBq) per plaque segment with respect to histological analysis revealed the co-localisation between hot regions of uptake and high area fractions of the inflammatory cells. LFA-1 uptake was significantly higher compared to the SSTR-2 receptor and this measurement was further verified through histological analysis. Subsequently, a quantitative metric based on the extent of the two interrelated inflammation targets was developed. Simultaneous dual-radiotracer SPECT imaging of 99m-Tc and 111-In labelled radiotracers can be utilised to quantify the intricate interplay between the inflammatory processes in human diseased arteries.