Systematically evaluating DOTATATE and FDG as PET immuno-imaging tracers of cardiovascular inflammation

Autor: Georgios Soultanidis, Jordi Ochando, Elizabeth L. Fisher, Zahi A. Fayad, Claudia Calcagno, Jazz Munitz, Mandy M. T. van Leent, Sonum Naidu, Carlos Perez-Medina, Chiara Giannarelli, Ken Sakurai, Adam Ali Ghotbi, Stefan Jordan, Farideh Ordikhani, Jason M. Tarkin, Yohana C. Toner, Nathaniel A. T. Sullivan, Alexander Maier, James H. F. Rudd, Christian Mason, Thomas Reiner, Max L. Senders, Letizia Amadori, Alexandros Marios Sofias, Willem Jan Menno Mulder, Andreas Kjaer
Přispěvatelé: Tarkin, Jason [0000-0002-9132-120X], Rudd, James [0000-0003-2243-3117], Apollo - University of Cambridge Repository, Lundbeck Foundation, Deutsche Forschungsgemeinschaft (Alemania), Wellcome Trust, NIHR - Cambridge Biomedical Research Center, British Heart Foundation, Higher Education Funding Council for England, Engineering and Physical Sciences Research Council (Reino Unido), NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos), National Center for Advancing Translational Sciences (Estados Unidos), ACS - Atherosclerosis & ischemic syndromes, AII - Inflammatory diseases, ACS - Amsterdam Cardiovascular Sciences, Medical Biochemistry
Rok vydání: 2022
Předmět:
Zdroj: Scientific reports, 12(1):6185. Nature Publishing Group
Scientific Reports
Scientific Reports, 12
Scientific Reports, 12, 1
Toner, Y C, Ghotbi, A A, Naidu, S, Sakurai, K, van Leent, M M T, Jordan, S, Ordikhani, F, Amadori, L, Sofias, A M, Fisher, E L, Maier, A, Sullivan, N, Munitz, J, Senders, M L, Mason, C, Reiner, T, Soultanidis, G, Tarkin, J M, Rudd, J H F, Giannarelli, C, Ochando, J, Pérez-Medina, C, Kjaer, A, Mulder, W J M, Fayad, Z A & Calcagno, C 2022, ' Systematically evaluating DOTATATE and FDG as PET immuno-imaging tracers of cardiovascular inflammation ', Scientific Reports, vol. 12, no. 1, 6185 . https://doi.org/10.1038/s41598-022-09590-2
Repisalud
Instituto de Salud Carlos III (ISCIII)
ISSN: 2045-2322
Popis: Funder: Engineering and Physical Sciences Research Council
Funder: Higher Education Funding Council for England
Funder: NIHR Cambridge Biomedical Research Centre
Funder: British Heart Foundation
In recent years, cardiovascular immuno-imaging by positron emission tomography (PET) has undergone tremendous progress in preclinical settings. Clinically, two approved PET tracers hold great potential for inflammation imaging in cardiovascular patients, namely FDG and DOTATATE. While the former is a widely applied metabolic tracer, DOTATATE is a relatively new PET tracer targeting the somatostatin receptor 2 (SST2). In the current study, we performed a detailed, head-to-head comparison of DOTATATE-based radiotracers and [18F]F-FDG in mouse and rabbit models of cardiovascular inflammation. For mouse experiments, we labeled DOTATATE with the long-lived isotope [64Cu]Cu to enable studying the tracer's mode of action by complementing in vivo PET/CT experiments with thorough ex vivo immunological analyses. For translational PET/MRI rabbit studies, we employed the more widely clinically used [68Ga]Ga-labeled DOTATATE, which was approved by the FDA in 2016. DOTATATE's pharmacokinetics and timed biodistribution were determined in control and atherosclerotic mice and rabbits by ex vivo gamma counting of blood and organs. Additionally, we performed in vivo PET/CT experiments in mice with atherosclerosis, mice subjected to myocardial infarction and control animals, using both [64Cu]Cu-DOTATATE and [18F]F-FDG. To evaluate differences in the tracers' cellular specificity, we performed ensuing ex vivo flow cytometry and gamma counting. In mice subjected to myocardial infarction, in vivo [64Cu]Cu-DOTATATE PET showed higher differential uptake between infarcted (SUVmax 1.3, IQR, 1.2-1.4, N = 4) and remote myocardium (SUVmax 0.7, IQR, 0.5-0.8, N = 4, p = 0.0286), and with respect to controls (SUVmax 0.6, IQR, 0.5-0.7, N = 4, p = 0.0286), than [18F]F-FDG PET. In atherosclerotic mice, [64Cu]Cu-DOTATATE PET aortic signal, but not [18F]F-FDG PET, was higher compared to controls (SUVmax 1.1, IQR, 0.9-1.3 and 0.5, IQR, 0.5-0.6, respectively, N = 4, p = 0.0286). In both models, [64Cu]Cu-DOTATATE demonstrated preferential accumulation in macrophages with respect to other myeloid cells, while [18F]F-FDG was taken up by macrophages and other leukocytes. In a translational PET/MRI study in atherosclerotic rabbits, we then compared [68Ga]Ga-DOTATATE and [18F]F-FDG for the assessment of aortic inflammation, combined with ex vivo radiometric assays and near-infrared imaging of macrophage burden. Rabbit experiments showed significantly higher aortic accumulation of both [68Ga]Ga-DOTATATE and [18F]F-FDG in atherosclerotic (SUVmax 0.415, IQR, 0.338-0.499, N = 32 and 0.446, IQR, 0.387-0.536, N = 27, respectively) compared to control animals (SUVmax 0.253, IQR, 0.197-0.285, p = 0.0002, N = 10 and 0.349, IQR, 0.299-0.423, p = 0.0159, N = 11, respectively). In conclusion, we present a detailed, head-to-head comparison of the novel SST2-specific tracer DOTATATE and the validated metabolic tracer [18F]F-FDG for the evaluation of inflammation in small animal models of cardiovascular disease. Our results support further investigations on the use of DOTATATE to assess cardiovascular inflammation as a complementary readout to the widely used [18F]F-FDG.
Databáze: OpenAIRE
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