XTR-003

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.

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.

Only two treatment-related adverse events occurred with no severe adverse effects. After tracer injection, XTR003 in the plasma peaked at 2.883 minutes as .0108235% of injected dose per gram (%ID/g) and reduced to the minimum at 30 minutes. The 0-20 minutes whole-body PET images indicated that both heart and liver were two critical organs with the highest percentage of injected dose (%ID) (4.37 ± .66 and 48.76 ± 4.17 %ID). Specifically, XTR003 demonstrated high initial uptake in the heart, with sustained retention for up to 290 minutes (standardized uptake value: 6.50 ± 2.54 at 0-20 minutes and 5.89 ± 2.18 at 270-290 minutes). The whole-body effective radiation dose was 17 μSv/MBq. The cumulative urinary excretion was 9.009%.

XTR003, as an¹⁸F-labeled 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.

ClinicalTrials.gov Identifier: NCT05136391.