Targeting post-infarct inflammation by PET imaging: comparison of 68Ga-citrate and 68Ga-DOTATATE with 18F-FDG in a mouse model

James T. Thackeray, Jens P. Bankstahl, Yong Wang, Mortimer Korf-Klingebiel, Almut Walte, Alexander Wittneben, Kai C. Wollert, Frank M. Bengel

Research output: Contribution to journalArticle

Abstract

ᅟ: Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. 18F-FDG PET has been used, but may be complicated by physiological myocyte uptake. We evaluated the potential of two alternative imaging targets: lactoferrin binding by 68Ga-citrate and somatostatin receptor binding by 68Ga-DOTATATE.

Methods: C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 – 7 days after MI using 68Ga-citrate, 68Ga-DOTATATE, or 18F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by 13N-ammonia PET and cardiac geometry by contrast-enhanced ECG-gated CT.

Results: Mice exhibited a perfusion defect of 30 – 40 % (of the total left ventricle) with apical anterolateral wall akinesia and thinning on day 7 after MI. 18F-FDG with ketamine/xylazine suppression demonstrated distinct uptake in the infarct region, as well as in the border zone and remote myocardium. The myocardial standardized uptake value in MI mice was significantly higher than in healthy mice under ketamine/xylazine anaesthesia (1.9 ± 0.4 vs. 1.0 ± 0.1). 68Ga images exhibited high blood pool activity with no specific myocardial uptake up to 90 min after injection (tissue-to-blood contrast 0.9). 68Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 ± 0.03).

Conclusion: Neither 68Ga nor 68Ga-DOTATATE is a useful alternative to 18F-FDG for PET imaging of myocardial inflammation after MI in mice. Among the three tested approaches, 18F-FDG with ketamine/xylazine suppression of cardiomyocyte uptake remains the most practical imaging marker of post-infarct inflammation.

Original languageEnglish (US)
Pages (from-to)317-327
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume42
Issue number2
DOIs
StatePublished - 2014
Externally publishedYes

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Fluorodeoxyglucose F18
Xylazine
Citric Acid
Ketamine
Myocardial Infarction
Inflammation
Muscle Cells
Perfusion
Somatostatin Receptors
Lactoferrin
Ammonia
Cardiac Myocytes
Heart Ventricles
Ligation
Coronary Vessels
Myocardium
Electrocardiography
Anesthesia
68Ga-DOTATATE
Glucose

Keywords

  • Inflammation
  • Molecular imaging
  • Myocardial infarction
  • Myocardial regeneration
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

Targeting post-infarct inflammation by PET imaging : comparison of 68Ga-citrate and 68Ga-DOTATATE with 18F-FDG in a mouse model. / Thackeray, James T.; Bankstahl, Jens P.; Wang, Yong; Korf-Klingebiel, Mortimer; Walte, Almut; Wittneben, Alexander; Wollert, Kai C.; Bengel, Frank M.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 42, No. 2, 2014, p. 317-327.

Research output: Contribution to journalArticle

Thackeray, James T. ; Bankstahl, Jens P. ; Wang, Yong ; Korf-Klingebiel, Mortimer ; Walte, Almut ; Wittneben, Alexander ; Wollert, Kai C. ; Bengel, Frank M. / Targeting post-infarct inflammation by PET imaging : comparison of 68Ga-citrate and 68Ga-DOTATATE with 18F-FDG in a mouse model. In: European Journal of Nuclear Medicine and Molecular Imaging. 2014 ; Vol. 42, No. 2. pp. 317-327.
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abstract = "ᅟ: Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. 18F-FDG PET has been used, but may be complicated by physiological myocyte uptake. We evaluated the potential of two alternative imaging targets: lactoferrin binding by 68Ga-citrate and somatostatin receptor binding by 68Ga-DOTATATE.Methods: C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 – 7 days after MI using 68Ga-citrate, 68Ga-DOTATATE, or 18F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by 13N-ammonia PET and cardiac geometry by contrast-enhanced ECG-gated CT.Results: Mice exhibited a perfusion defect of 30 – 40 {\%} (of the total left ventricle) with apical anterolateral wall akinesia and thinning on day 7 after MI. 18F-FDG with ketamine/xylazine suppression demonstrated distinct uptake in the infarct region, as well as in the border zone and remote myocardium. The myocardial standardized uptake value in MI mice was significantly higher than in healthy mice under ketamine/xylazine anaesthesia (1.9 ± 0.4 vs. 1.0 ± 0.1). 68Ga images exhibited high blood pool activity with no specific myocardial uptake up to 90 min after injection (tissue-to-blood contrast 0.9). 68Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 ± 0.03).Conclusion: Neither 68Ga nor 68Ga-DOTATATE is a useful alternative to 18F-FDG for PET imaging of myocardial inflammation after MI in mice. Among the three tested approaches, 18F-FDG with ketamine/xylazine suppression of cardiomyocyte uptake remains the most practical imaging marker of post-infarct inflammation.",
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AU - Bankstahl, Jens P.

AU - Wang, Yong

AU - Korf-Klingebiel, Mortimer

AU - Walte, Almut

AU - Wittneben, Alexander

AU - Wollert, Kai C.

AU - Bengel, Frank M.

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N2 - ᅟ: Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. 18F-FDG PET has been used, but may be complicated by physiological myocyte uptake. We evaluated the potential of two alternative imaging targets: lactoferrin binding by 68Ga-citrate and somatostatin receptor binding by 68Ga-DOTATATE.Methods: C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 – 7 days after MI using 68Ga-citrate, 68Ga-DOTATATE, or 18F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by 13N-ammonia PET and cardiac geometry by contrast-enhanced ECG-gated CT.Results: Mice exhibited a perfusion defect of 30 – 40 % (of the total left ventricle) with apical anterolateral wall akinesia and thinning on day 7 after MI. 18F-FDG with ketamine/xylazine suppression demonstrated distinct uptake in the infarct region, as well as in the border zone and remote myocardium. The myocardial standardized uptake value in MI mice was significantly higher than in healthy mice under ketamine/xylazine anaesthesia (1.9 ± 0.4 vs. 1.0 ± 0.1). 68Ga images exhibited high blood pool activity with no specific myocardial uptake up to 90 min after injection (tissue-to-blood contrast 0.9). 68Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 ± 0.03).Conclusion: Neither 68Ga nor 68Ga-DOTATATE is a useful alternative to 18F-FDG for PET imaging of myocardial inflammation after MI in mice. Among the three tested approaches, 18F-FDG with ketamine/xylazine suppression of cardiomyocyte uptake remains the most practical imaging marker of post-infarct inflammation.

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