Abstract 460: 64 Cu-DOTATATE for in vivo Positron Emission Tomography Imaging of Somatostatin Receptor 2 Expressing Macrophages in a Göttingen Minipig Model of Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sune Folke Pedersen ◽  
Trine Pagh Ludvigsen ◽  
Andreas Vegge ◽  
Camilla Schumacher-Petersen ◽  
Rasmus Sejersten Ripa ◽  
...  

Background: Somatostatin receptor subtype 2 (SSTR 2 ) is expressed by activated macrophages which are important effector cells in atherogenesis and a major constituent of atherosclerotic plaques. SSTR 2 can be targeted non-invasively in vivo using the tracer 64 Cu-DOTATATE and positron emission tomography (PET). Methods: Male castrated Göttingen minipigs were treated according to two diet regimes for 43 weeks: chow (lean control; n=1) or high-fat/high-cholesterol diet (HFHC, obese group; n=2). Plasma lipids: total cholesterol (TC) and triglycerides (TG) were measured and SSTR 2 expression was assessed using hybrid positron emission tomography/magnetic resonance (PET/MR) imaging of the abdominal aorta, one hour (range: 60-63 minutes) post injection with 200 MBq (range 202-214 MBq) of 64 Cu-DOTATATE. Consectutive regions of interest (ROIs) were drawn guided by MR to include vessel wall and lumen of the abdominal aorta to calculate standardized uptake values (SUVs). Target-to-background (TBR) ratios were calculated using right atrium SUVs for blood pool correction (SUV vessel /SUV right atrium = TBR) and reported as mean and maximal values (TBR mean ; TBR max ). Results: Three minipigs (age 17 months) were included and PET/MR was completed in all animals. Mean uptake of 64 Cu-DOTATATE was lowest for the abdominal aorta in the lean control: TBR mean = 0.44 and TBR max = 0.73 (range: TBR mean = 0.29 - 0.62; TBR max = 0.49 - 1.10) and highest in the HFHC group: TBR mean = 0.66 and TBR max = 1.28 (range: TBR mean = 0.26 - 1.38; TBR max = 0.39 - 3.19). Plasma lipids: lean control: TC = 1.34 mmol/L; TG = 0.38 mmol/L; HFHC group (mean values): TC = 18.7mmol/L (range: 11.6 - 25.8mmol/L); TG = 0.6 mmol/L (range: 0.37 - 0.83mmol/L). Conclusion: Non-invasive 64 Cu-DOTATATE PET/MR is feasible for assessment of SSTR 2 expression in a Göttingen minipig model of diet-induced atherosclerosis. Additional studies are needed including assessment of histology findings and gene expression to confirm the presence of activated macrophages in order to validate the use of 64 Cu-DOTATATE PET/MR in this model.

Author(s):  
Paula Nogales ◽  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Leticia González-Cintado ◽  
Rubén Avelino Mota ◽  
...  

Objective: 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) imaging is thought to visualize active atherosclerotic plaque calcification. This is supported by the binding of 18 F-NaF to plaque calcification ex vivo, but no prior studies have examined binding of 18 F-NaF to human-like plaque in vivo. Our aim was to validate the specificity of 18 F-NaF PET for plaque calcifications in atherosclerotic minipigs. Approach and Results: Gain-of-function PCSK9 D374Y (proprotein convertase/subtilisin kexin type 9) transgenic Yucatan minipigs (n=4) were fed high-fat diet for 2.5 years to develop atherosclerosis and then subjected to 18 F-NaF PET/computed tomography imaging. The heart, aorta, and iliac arteries were immediately re-scanned ex vivo after surgical extraction. Lesions from the abdominal aorta, iliac arteries, and coronary arteries were cryo-sectioned for autoradiography. Histological plaque characteristics, PET/computed tomography signal, and autoradiography were linked through regression and co-localization analysis. Arterial 18 F-NaF PET signal had intensities comparable to clinical scans and colocalized moderately with calcification detected by computed tomography. Histological analysis showed calcification spanning from microcalcifications near lipid pools and necrotic core to more homogenous macrocalcifications. Comparison with arteries from autopsy cases confirmed the resemblance in localization and appearance with early human plaque calcification. Regression analysis in the abdominal aorta showed correlations with calcified plaque but could not rule out contributions from noncalcified plaque. This was resolved by autoradiography, which showed specific accumulation in plaque calcifications in all examined arteries. In the context of porcine abdominal aorta, 18 F-NaF PET imaging was, however, less accurate than computed tomography for detecting small calcifications. Conclusions: 18 F-NaF accumulates specifically in calcifications of atherosclerotic plaques in vivo.


2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Johannes Notni ◽  
Florian T. Gassert ◽  
Katja Steiger ◽  
Peter Sommer ◽  
Wilko Weichert ◽  
...  

Following publication of the original article [1], the authors have reported an error in the ‘Histopathology’ (under ‘Materials and methods’) section of the article that compromises the reproducibility of the paper.


1996 ◽  
Vol 84 (3) ◽  
pp. 494-502 ◽  
Author(s):  
Bernhard Zünkeler ◽  
Richard E. Carson ◽  
Jeffrey Olson ◽  
Ronald G. Blasberg ◽  
Mary Girton ◽  
...  

✓ Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8- to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 ± 2.4 µl/min/ml (± standard deviation) at baseline and increased more than 100% (ΔK1 = 9.4 ± 5.1 µl/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p < 0.005). Vascular permeability returned to baseline with a halftime of 24.0 ± 14.3 minutes. The mean brain plasma volume rose by 0.57 ± 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.


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