title: 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: 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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: James T
authors.initials: JT
authors.lastname: Thackeray
authors.forename: Jens P
authors.initials: JP
authors.lastname: Bankstahl
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Mortimer
authors.initials: M
authors.lastname: Korf-Klingebiel
authors.forename: Almut
authors.initials: A
authors.lastname: Walte
authors.forename: Alexander
authors.initials: A
authors.lastname: Wittneben
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.forename: Frank M
authors.initials: FM
authors.lastname: Bengel
mesh_terms: D000818:Animals; D002951:Citrates / Q000493:pharmacokinetics*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005708:Gallium / Q000493:pharmacokinetics*; D007249:Inflammation / Q000000981:diagnostic imaging; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D055414:Myocardial Perfusion Imaging; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D002951:Citrates; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C513399:gallium Ga 68 dotatate; D005708:Gallium; C103850:gallium citrate
references.citation: Eur J Nucl Med Mol Imaging. 2012 Feb;39 Suppl 1:S68-77
references.pmid: 22388620
references.citation: J Mol Cell Cardiol. 2014 Apr;69:32-42
references.pmid: 24508700
references.citation: J Am Coll Cardiol. 2012 Jan 10;59(2):153-63
references.pmid: 22222080
references.citation: J Nucl Cardiol. 2011 Oct;18(5):926-36
references.pmid: 21732228
references.citation: PLoS One. 2012;7(5):e37506
references.pmid: 22624041
references.citation: Nat Med. 2011 May;17(5):581-8
references.pmid: 21516086
references.citation: Hum Gene Ther. 2011 Feb;22(2):189-96
references.pmid: 20825281
references.citation: Eur J Heart Fail. 2010 Jul;12(7):653-8
references.pmid: 20495202
references.citation: Biochem J. 1997 Oct 15;327 ( Pt 2):369-75
references.pmid: 9359403
references.citation: J Nucl Cardiol. 2012 Aug;19(4):775-84
references.pmid: 22527796
references.citation: J Neuroimmunol. 2003 May;138(1-2):38-44
references.pmid: 12742651
references.citation: EJNMMI Res. 2012 Sep 27;2(1):52
references.pmid: 23016793
references.citation: J Nucl Med. 2012 Apr;53(4):575-83
references.pmid: 22419753
references.citation: Eur Heart J Cardiovasc Imaging. 2013 Aug;14(8):741-51
references.pmid: 23720377
references.citation: J Am Coll Cardiol. 2013 Dec 17;62(24):2344-5
references.pmid: 24076295
references.citation: J Med Imaging Radiat Oncol. 2012 Feb;56(1):40-7
references.pmid: 22339744
references.citation: EJNMMI Res. 2011 Aug 17;1(1):14
references.pmid: 22214258
references.citation: Intern Emerg Med. 2012 Feb;7(1):53-8
references.pmid: 22167445
references.citation: J Leukoc Biol. 2007 Mar;81(3):845-55
references.pmid: 17148691
references.citation: J Nucl Med. 2011 Nov;52(11):1795-802
references.pmid: 21969358
references.citation: Circulation. 2011 Feb 8;123(5):504-14
references.pmid: 21262993
references.citation: J Mol Med (Berl). 2012 Apr;90(4):361-9
references.pmid: 22228177
references.citation: Semin Nucl Med. 2009 Mar;39(2):124-45
references.pmid: 19187805
references.citation: Exp Biol Med (Maywood). 2005 Nov;230(10):777-84
references.pmid: 16246906
references.citation: Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E166-74
references.pmid: 16926380
references.citation: Eur J Nucl Med Mol Imaging. 2010 Nov;37(11):2079-85
references.pmid: 20603720
references.citation: Circulation. 2002 Jun 11;105(23):2708-11
references.pmid: 12057982
references.citation: J Nucl Med. 2010 Feb;51(2):193-7
references.pmid: 20080898
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19725-30
references.pmid: 22106299
references.citation: Science. 2013 Jan 11;339(6116):161-6
references.pmid: 23307733
references.citation: J Nucl Med. 2009 Dec;50(12):1927-32
references.pmid: 19910422