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 5 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 5 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 5 0.97x11.5, R 2 5 0.94, y 5 blue-dye defect, x 5 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 5 0.19 6 0.02, 0.19 6 0.05, and 0.34 6 0.06 at 5, 45, and 120 min, respectively, P , 0.05). For comparison, 201 Tl showed complete redistribution at 120 min (LCA/remote 5 0.42 6 0.04, 0.72 6 0.03, and 0.97 6 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. PET myocardial perfusion imaging is increasingly entering the clinical arena as a highly accurate technique for the workup of coronary artery disease (1,2). When compared with standard SPECT, it provides better temporal and spatial resolution, higher sensitivity for tracer detection, and robust correction of attenuation artifacts (3,4). The currently established PET myocardial perfusion tracers include 82 Rb-rubidium chloride, 13 N-ammonia, and 15 Owater, but their short radioactive half-lives (76 s, 10 min, and 2.1 min, respectively) require expensive on-site production by a cyclotron or commitment to a dedicated generator. Additionally, a physical-exercise stress test is not practical because of the rapid decay of these tracers.18 F-fluorobenzyl triphenyl phosphonium (FBnTP) is one of several recently introduced 18 F-labeled perfusion tracers. It is a cation with a mechanism of uptake similar to 99m Tctetrofosmin and 99m Tc-sestamibi and has shown promising properties such as high cardiac uptake and retention in animal models (5-8). Because of t...

Comparison of the Cardiac MicroPET Images Obtained Using [18F]FPTP and [13N]NH3 in Rat Myocardial Infarction Models

“…7,8 To address this need, we have developed 18 Figure 2A,B. In normal rats, microPET imaging demonstrated intense, homogeneous uptake of [ 18 F]FPTP through the myocardium and excellent myocardium-to-liver and myocardium-to-lung contrast 10 min after tracer injection.…”

PET myocardial perfusion quantification: anatomy of a spreading functional technique

“…A full 82 Rb 3D PET scan implies an exposure of ≈ 4.3 mSv, while for a single 13 N-ammonia 3D scan, the estimated the radiation dose is around 1, and 0.8 mSv for 15 O-H 2 O [9]. The calculated exposure for 18 F-flurpiridaz has initially been estimated in 6.3 mSv [7].…”

“…Another major study, the PACIFIC trial, demonstrated directly that 15 O-H 2 O PET conveys the best diagnostic performance (in comparison to SPECT and CCTA) with a sensitivity of 87% and a specificity of 84% for the detection of functionally significant lesions evaluated by fractional flow reserve (FFR) [30], the current gold standard for the functional assessment of coronary stenosis [31]. Figure 3 depicts a typical patient with intermediate risk of CAD investigated for myocardial ischemia.…”

“…18 Fluorine-labeled phosphonium derivates ( 18 F-FATPs) have demonstrated potential for PET MPI in preclinical studies. 18 F-FATPs accumulate in cardiac myocytes due to their higher mitochondrial membrane potential and show intense myocardial uptake with sharp delineation of perfusion defects in animal models [15]. 18 F-FATPs have been compared to 13 N-ammonia and favorable warrant further extension into clinical studies in the coming years [16].…”

“…With 15 O-H 2 O and 82 Rb, the second phase can be performed without delay after the first study. However, with 13 N-ammonia the second study (stress or rest) is routinely delayed 30 min after the first study, to allow for radiotracer decay and the image acquisition is started a few seconds before the radiotracer injection.…”