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

Abstract

UNLABELLED:

Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. (18)F-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 (68)Ga-citrate and somatostatin receptor binding by (68)Ga-DOTATATE.

METHODS:

C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 - 7 days after MI using (68)Ga-citrate, (68)Ga-DOTATATE, or (18)F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by (13)N-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. (18)F-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). (68)Ga images exhibited high blood pool activity with no specific myocardial uptake up to 90 min after injection (tissue-to-blood contrast 0.9). (68)Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 ± 0.03).

CONCLUSION:

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

• Authors: James T Thackeray, Jens P Bankstahl, Yong Wang, Mortimer Korf-Klingebiel, Almut Walte, Alexander Wittneben, Kai C Wollert, Frank M Bengel
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 42 Issue 2 Pg. 317-27 (Feb 2015) ISSN: 1619-7089 [Electronic] Germany
• PMID: 25112398 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Citrates
• Organometallic Compounds
• Radiopharmaceuticals
• Fluorodeoxyglucose F18
• gallium Ga 68 dotatate
• Gallium
• gallium citrate

Topics

• Animals
• Citrates (pharmacokinetics)
• Fluorodeoxyglucose F18 (pharmacokinetics)
• Gallium (pharmacokinetics)
• Inflammation (diagnostic imaging)
• Metabolic Clearance Rate
• Mice
• Mice, Inbred C57BL
• Myocardial Infarction (complications, diagnostic imaging, pathology)
• Myocardial Perfusion Imaging
• Organometallic Compounds (pharmacokinetics)
• Positron-Emission Tomography
• Radiopharmaceuticals (pharmacokinetics)