Comparison of ¹⁸F-Labeled Fluoroalkylphosphonium Cations with ¹³N-NH₃ for PET Myocardial Perfusion Imaging

Abstract

Despite substantial advances in the diagnosis of cardiovascular disease, there is a need for 18 F-labeled myocardial perfusion agents for the diagnosis of ischemic heart disease because current PET tracers for myocardial perfusion imaging have a short half-life that limits their widespread clinical use in PET. Thus, 18 F-labeled fluoroalkylphosphonium derivatives ( 18 F-FATPs), including (5-18 F-fluoropentyl)triphenylphosphonium cation ( 18 F-FPTP), (6-18 F-fluorohexyl)triphenylphosphonium cation ( 18 F-FHTP), and (2-(2-18 F-fluoroethoxy)ethyl)triphenylphosphonium cation ( 18 F-FETP), were synthesized. The myocardial extraction and image quality of the 18 F-FATPs were compared with those of 13 N-NH 3 in rat models. Methods: The first-pass extraction fraction (EF) values of the 18 F-FATPs ( 18 F-FPTP, 18 F-FHTP, 18 F-FETP) and 13 N-NH 3 were measured in isolated rat hearts perfused with the Langendorff method (flow velocities, 0.5, 4.0, 8.0, and 16.0 mL/min). Normal and myocardial infarction rats were imaged with small-animal PET after intravenous injection of 37 MBq of 18 F-FATPs and 13 N-NH 3. To determine pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of the 18 F-FATPs and 13 N-NH 3 were generated to obtain the counts per pixel per second. Defect size was analyzed on the basis of polar map images of 18 F-FATPs and 13 N-NH 3. Results:The EF values of 18 F-FATPs and 13 N-NH 3 were comparable at low flow velocity (0.5 mL/min), whereas at higher flows EF values of 18 F-FATPs were significantly higher than those of 13 N-NH 3 (4.0, 8.0, and 16.0 mL/min, P , 0.05). Myocardium-to-liver ratios of 18 F-FPTP, 18 F-FHTP, 18 F-FETP, and 13 N-NH 3 were 2.10 ± 0.30, 4.36 ± 0.20, 3.88 ± 1.03, and 0.70 ± 0.09, respectively, 10 min after injection, whereas myocardium-to-lung ratios were 5.00 ± 0.25, 4.33 ± 0.20, 7.98 ± 1.23, and 2.26 ± 0.14, respectively. Although 18 F-FATPs and 13 N-NH 3 sharply delineated myocardial perfusion defects, defect size on the 13 N-NH 3 images was significantly smaller than on the 18 F-FATP images soon after tracer injection (0-10 min, P 5 0.027). Conclusion: 18 F-FATPs exhibit higher EF values and more rapid clearance from the liver and lung than 13 N-NH 3 in normal rats, which led to excellent image quality in a rat model of coronary occlusion. Therefore, 18 FFATPs are promising new PET radiopharmaceuticals for myocardial perfusion imaging.

Promising New 18F-Labeled Tracers for PET Myocardial Perfusion Imaging

“…In a preclinical study appearing in this issue of The Journal of Nuclear Medicine, Kim and colleagues assess the suitability of 3 18 F-labeled fluoroalkylphosphonium salts for PET myocardial perfusion imaging (11). Similar to 99m Tc-sestamibi and 99m Tc-tetrofosmin, these moieties depend on high mitochondrial membrane potentials for retention in cardiac myocytes.…”

Comparative evaluation of the algorithms for parametric mapping of the novel myocardial PET imaging agent 18F-FPTP

“…Figure 1) [13–15]. It was also shown that 18 F-FPTP has greater first-pass myocardial extraction than 13 N-ammonia in isolated perfused rat heart, indicating the suitability of 18 F-FPTP as a quantitative myocardial PET imaging agent [14, 15]. In addition, no metabolite was detected in the serum of mice 30 min after intravenous injection of 18 F-FPTP, implying that the metabolite correction would not be necessary in the kinetic analysis of 18 F-FPTP myocardial PET data [13].…”

Flow-Based Functional Assessment of Coronary Artery Disease by Myocardial Perfusion Positron Emission Tomography in the Era of Fractional Flow Reserve

“…PET-measured MBF has shown excellent agreement with that measured by microsphere injection and invasive activity measurement (18)(19)(20)(21)(22). MBF can be measured by compartment modeling and estimation of rate constant values among tissue compartments ( Fig.…”