Evaluation of 18F-Rho6G as a Novel PET Tracer for Myocardial Perfusion Imaging in a Swine Ischemia Reperfusion Model.

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235 Objectives: Myocardial perfusion imaging is routinely used for assessment of relative blood flow in the detection of coronary artery disease and for risk-stratification. PET imaging offers intrinsic advantages in spatial resolution and sensitivity. However, currently available FDA approved PET perfusion agents have short half-lives requiring an on-site generator or cyclotron. We sought to evaluate a new perfusion agent based on an 18F-labeled rhodamine dye (18F-Rho6G) and to determine the myocardial extraction fraction and subsequent biodistribution in a swine ischemia-reperfusion model. Methods: 18F-Rho6G was produced as previously described1 with minor modification, in high specific activity (range 186-840 MBq/nmol) and high radiochemical purity (>90%). We first determined the in vivo first pass myocardial extraction fraction (FPMEF) of 18F-Rho6G in male Yorkshire swine (n=4) by intracoronary co-injection of 18F-Rho6G (8.14 ± 1.04 MBq) and 131I-albumin (0.296 ± 0.185) via a guide catheter placed in the left main coronary over 20 seconds, and simultaneous withdraw of serial 1 mL blood every 5 seconds for 2 minutes from a multipurpose catheter placed in the coronary sinus. To determine the FPMEF, the area under the activity curves for both tracers was calculated correcting for the ratio of injected activity, and counting efficiency of each isotope on the gamma counter. Following evaluation of FPMEF, one swine underwent a 90 min balloon occlusion and five days later underwent dynamic cardiac PET imaging on a Siemens Biograph mCT scanner to determine the biodistribution and clearance of the radiotracer under resting conditions over 60 minutes. The reconstructed cardiac PET images were merged with a contrast CT image for drawing of regions of interest (ROIs) using Carimas Version 2.9 (Turku, Finland). Results: The FPMEF of 18F-Rho6G was calculated at 79.4 ± 7.1 %. Under resting conditions, 18F-Rho6G demonstrated favorable cardiac imaging characteristics (Figure 1) with high uptake and retention in the myocardium, with a heart to blood ratio of 15.67, heart to liver ratio of 1.44, heart to lung ratio of 11.79, and heart to bone ratio of 1.33, all at 45-60 min post-injection. The uptake of the radiotracer was approximately 2.5 fold higher in the LV remote zone vs. the infarct territory at rest. Conclusions: 18F-Rho6G appears to be a highly promising 18F-labeled myocardial perfusion tracer with a high first pass myocardial extraction fraction and favorable heart to background tissue uptake patterns in a clinically relevant large animal model. Additional dynamic rest and stress 18F-Rho6G imaging studies are underway for determination of absolute flow in comparison to 15O-water and radioactive microspheres.

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