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

Abstract

UNLABELLED:

(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.

CONCLUSION:

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: Takahiro Higuchi, Kenji Fukushima, Christoph Rischpler, Takuro Isoda, Mehrbod S Javadi, Hayden Ravert, Daniel P Holt, Robert F Dannals, Igal Madar, Frank M Bengel
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 52 Issue 6 Pg. 965-9 (Jun 2011) ISSN: 1535-5667 [Electronic] United States
• PMID: 21571789 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 18F-fluorobenzyl triphenyl phosphonium
• Organophosphorus Compounds
• Radiopharmaceuticals
• Thallium Radioisotopes

Topics

• Animals
• Autoradiography
• Coronary Occlusion (diagnostic imaging)
• Coronary Vessels (physiology)
• Male
• Organophosphorus Compounds (pharmacokinetics)
• Positron-Emission Tomography
• Radiopharmaceuticals (pharmacokinetics)
• Rats
• Rats, Wistar
• Thallium Radioisotopes