Stable delineation of the ischemic area by the PET perfusion tracer 18F-fluorobenzyl triphenyl phosphonium after transient coronary occlusion

Takahiro Higuchi, Kenji Fukushima, Christoph Rischpler, Takuro Isoda, Mehrbod S. Javadi, Hayden Ravert, Daniel P. Holt, Robert F. Dannals, Igal Madar, Frank Michael Bengel

Research output: Contribution to journalArticle

Abstract

18F-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, 18F-FBnTP (92.5 MBq) and 201Tl-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 18F-FBnTP PET was performed on a subgroup of animals (n = 4). Results: 18F-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, R2 = 0.94, y = blue-dye defect, x = 18F-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, 201Tl 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 18F-FBnTP defect over time was confirmed by in vivo dynamic small-animal PET. Conclusion: In a transient coronary occlusion model, perfusion defect size using the new PET agent 18F-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.

Original languageEnglish (US)
Pages (from-to)965-969
Number of pages5
JournalJournal of Nuclear Medicine
Volume52
Issue number6
DOIs
StatePublished - Jun 1 2011

Keywords

  • Animal imaging
  • Autoradiography
  • Cardiology (basic/technical)
  • Molecular imaging
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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