XTR003, a Fatty-acid Metabolism PET Tracer: A Phase I Study to Evaluate the Safety, Biodistribution, Radiation Dosimetry and Pharmacokinetics in Healthy Volunteers.
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Abstract
Purpose: XTR003 is a novel 18F-labeled fatty-acid PET tracer to image myocardial fatty-acid metabolism that can be potentially used to assess myocardial viability for ischemic heart disease. This Phase I study evaluated its safety, biodistribution, radiation dosimetry, and pharmacokinetics.
Methods: Ten healthy Chinese volunteers (mean age of 28.4±4.6 years, 3 females) were intravenously injected with XTR003 (296-370 MBq) at rest and monitored for adverse events on the day of injection and follow-up days. Multiple whole-body PET images were acquired within 290 minutes and processed to investigate the biodistribution and radiation dosimetry. Whole blood, plasma, and urine were collected simultaneously for 420 minutes to evaluate the pharmacokinetics with the measurement of radioactivity.
Results: Only two treatment-related adverse events occurred with no severe adverse effects. After tracer injection, XTR003 in the plasma peaked at 2.883 min as 0.0108235 percentage of injected dose per gram (%ID/g) and reduced to the minimum at 30 min. The 0-20 min whole-body PET images indicated that both heart and liver were two critical organs with the highest percentage of injected dose (%ID) (4.37±0.66 and 48.76±4.17 %ID). Specifically, XTR003 demonstrated high initial uptake in the heart, with sustained retention for up to 290 minutes (SUV: 6.50 ± 2.54 at 0-20 minutes and 5.89 ± 2.18 at 270-290 minutes). The whole-body effective radiation dose was 17μSv/MBq. The cumulative urinary excretion was 9.009%.
Conclusion: XTR003, as a 18F-labelled radiotracer, was safe and well-tolerated. The rapid uptake and prolonged retention of XTR003 in the heart show promise for evaluating myocardial fatty acid metabolism. The phase II clinical trial to explore the efficacy of XTR003 for detecting myocardial viability should be warranted.
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Journal of Nuclear Cardiology is the only journal in the world devoted to this dynamic and growing subspecialty. Physicians and technologists value the Journal not only for its peer-reviewed articles, but also for its timely discussions about the current and future role of nuclear cardiology. Original articles address all aspects of nuclear cardiology, including interpretation, diagnosis, imaging equipment, and use of radiopharmaceuticals. As the official publication of the American Society of Nuclear Cardiology, the Journal also brings readers the latest information emerging from the Society''s task forces and publishes guidelines and position papers as they are adopted.
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