title: Stable delineation of the ischemic area by the PET perfusion tracer 18F-fluorobenzyl triphenyl phosphonium after transient coronary occlusion.
abstract: (18)F-fluorobenzyl triphenyl phosphonium (FBnTP) has recently been introduced as a myocardial perfusion PET agent. We used a rat model of transient coronary occlusion to determine the stability of the perfusion defect size over time and the magnitude of redistribution.
  
  
  METHODS
  Wistar rats (n = 15) underwent thoracotomy and 2-min occlusion of the left coronary artery (LCA), followed by reperfusion. During occlusion, (18)F-FBnTP (92.5 MBq) and (201)Tl-thallium chloride (0.74 MBq) were injected intravenously. One minute before the animals were sacrificed at 5, 45, and 120 min after reperfusion, the LCA was occluded again and 2% Evans blue was injected intravenously to determine the ischemic territory. The hearts were excised, frozen, and sliced for serial dual-tracer autoradiography and histology. Dynamic in vivo (18)F-FBnTP PET was performed on a subgroup of animals (n = 4).
  
  
  RESULTS
  (18)F-FBnTP showed stable ischemic defects at all time points after tracer injection and reperfusion. The defects matched the blue dye defect (y = 0.97x+1.5, R(2) = 0.94, y = blue-dye defect, x = (18)F-FBnTP defect). Count density analysis showed no defect fill-in at 45 min but slightly increased activity at 120 min (LCA/remote uptake ratio = 0.19 ± 0.02, 0.19 ± 0.05, and 0.34 ± 0.06 at 5, 45, and 120 min, respectively, P < 0.05). For comparison, (201)Tl showed complete redistribution at 120 min (LCA/remote = 0.42 ± 0.04, 0.72 ± 0.03, and 0.97 ± 0.05 at 5, 45, and 120 min, respectively, P < 0.001). Persistence of the (18)F-FBnTP defect over time was confirmed by in vivo dynamic small-animal PET.
  
  
  CONCLUSIONS
  In a transient coronary occlusion model, perfusion defect size using the new PET agent (18)F-FBnTP remained stable for at least 45 min and matched the histologically defined ischemic area. This lack of significant redistribution suggests a sufficient time window for future clinical protocols with tracer injection remote from the scanner, such as in a stress testing laboratory or chest pain unit.
authors.affiliation: Division of Nuclear Medicine, Russell H Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukushima
authors.forename: Christoph
authors.initials: C
authors.lastname: Rischpler
authors.forename: Takuro
authors.initials: T
authors.lastname: Isoda
authors.forename: Mehrbod S
authors.initials: MS
authors.lastname: Javadi
authors.forename: Hayden
authors.initials: H
authors.lastname: Ravert
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Holt
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Igal
authors.initials: I
authors.lastname: Madar
authors.forename: Frank M
authors.initials: FM
authors.lastname: Bengel
mesh_terms: D000818:Animals; D001345:Autoradiography; D054059:Coronary Occlusion / Q000000981:diagnostic imaging*; D003331:Coronary Vessels / Q000502:physiology; D008297:Male; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013794:Thallium Radioisotopes
chemical_list: C513681:18F-fluorobenzyl triphenyl phosphonium; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; D013794:Thallium Radioisotopes