Quantitative assessment of coronary artery stenosis using the PET imaging compound F-18-fluorobenzyl triphenyl phosphonium: Comparison with Tc-99m-tetrofosmin

Abstract

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Objectives: F-18-Fluorobenzyl triphenyl phosphonium (FBnTP) is a lipophilic cation with excellent uptake, prolonged retention and uniform distribution in the myocardium, rapid blood clearance, very low lung uptake and liver uptake not exceeding LV wall activity. The capability of FBnTP to detect and quantify regional flow disparity was characterized in dogs with various degrees of coronary stenosis, during adenosine vasodilation.

Methods: 18 open-chest dogs with either complete ligation (n = 3), critical (n = 9) or mild (n = 6) stenosis of LCx or LAD. Microspheres (MS) were injected at baseline, stenosis and peak adenosine flow. Ten minutes after tracer injection, the heart was excised, monestral blue (MB) stained rings were photographed, sliced into small endocardial and epicardial segments and tissue radioactivity was counted. Ischemic-to-nonischemic (is/nis) ratio was calculated by counting tracers activity in two transmural segments showing the minimal and maximal adenosine blood flow, respectively. In 8/18 dogs, after stenosis was established, FBnTP (6 to 15 mCi) and Tc-99m-tetrofosmin (Tetro, 3 mCi) were injected IV and a 60 min dynamic scan was performed, followed by 25 min gated PET and contrast enhanced gated CT scan; and the myocardial rings were stained with MB and TTC. CT-based partial volume correction (PVC) of cardiac PET images, was performed. Extent of risk area of PET and MB stained rings was assessed by the planimetery method.

Results: A linear correlation (R2 = 0.934) was found between the ischemic-to-nonischemic (is/nis) activity ratio calculated by tissue counting for FBnTP and coronary flow during adenosine vasodilation, over the entire range of stenosis severities. Flow, FBnTP and Tetro is/nis ratio was 0.2, 0.42, 0.63 in sever stenosis, and 0.67, 0.82, 0.97 in mild stenosis. FBnTP better estimated flow disparity than Tetro in the low flow range. FBnTP high-quality images allowed visual distinction between severities of stenosis. Similar is/nis contrast was obtained by early, short (5-15 min); and later, longer (30-60 min), FBnTP images. Neither end-diastolic gated PET nor CT-based PVC improved significantly the is/nis ratio. In critical stenosis dogs, extent of PET and MB risk area correlated linearly (R2 = 0.97).

Conclusions: FBnTP demonstrated excellent characteristics for the detection and assessment of stenosis severity using PET imaging. The rapid kinetics permits detection of stenosis using early short scan, thus may improve patients management. These characteristics, combined with the favorable organ distribution and the technical superiority of the PET, may make this tracer attractive for translation to clinical use.