Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

DOI

  1. Exercise suppresses tumor growth independent of high fat food intake and associated immune dysfunction

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  2. Initial evidence of abnormal brain plasticity in anorexia nervosa: an ultra-high field study

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  3. Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  4. An explorative metabolomic analysis of the endothelium in pulmonary hypertension

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  • Yohana C. Toner
  • Adam A. Ghotbi
  • Sonum Naidu
  • Ken Sakurai
  • Mandy M.T. van Leent
  • Stefan Jordan
  • Farideh Ordikhani
  • Letizia Amadori
  • Alexandros Marios Sofias
  • Elizabeth L. Fisher
  • Alexander Maier
  • Nathaniel Sullivan
  • Jazz Munitz
  • Max L. Senders
  • Christian Mason
  • Thomas Reiner
  • Georgios Soultanidis
  • Jason M. Tarkin
  • James H.F. Rudd
  • Chiara Giannarelli
  • Jordi Ochando
  • Carlos Pérez-Medina
  • Andreas Kjaer
  • Willem J.M. Mulder
  • Zahi A. Fayad
  • Claudia Calcagno
Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummer6185
TidsskriftScientific Reports
Vol/bind12
Udgave nummer1
ISSN2045-2322
DOI
StatusUdgivet - dec. 2022

Bibliografisk note

Funding Information:
AAG was supported by The Lundbeck Foundation R251-2017-870. FO was supported by an Institutional Research Training Grant T32CA078207. AM was supported by Deutsche Forschungsgemeinschaft MA7059/1. TR was supported by MSK Cancer Center P30 P30 CA008748. JMT was supported by the Wellcome Trust (211100/Z/18/Z). JHFR is part-supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, Higher Education Funding Council for England, the Engineering and Physical Sciences Research Council and the Wellcome Trust. CG was supported by NIH-NHLBI R01 HL153712-01, NIH-NCATS UH3TR002067, American Heart Association 20SFRN35210252 and Chan Zuckerberg Initiative NFL-2020-218415. ZAF was supported by NIH/NHLBI R01 HL135878.

Publisher Copyright:
© 2022, The Author(s).

ID: 79408059