XTR003, a fatty acid metabolism PET tracer: A phase I study to evaluate the safety, biodistribution, radiation dosimetry, and pharmacokinetics in healthy volunteers

IF 3 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Nuclear Cardiology Pub Date : 2025-04-01 DOI:10.1016/j.nuclcard.2025.102144

Tiantian Mou PhD , Jingjing Meng MD, PhD , Chengyu Lin MD , Xiaofen Xie BS , Bailing Hsu PhD , Xiaoli Zhang MD, PhD

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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 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%.

Conclusions

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.

Trail registration number

ClinicalTrials.gov Identifier: NCT05136391.

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脂肪酸代谢PET示踪剂XTR003：健康志愿者安全性、生物分布、辐射剂量学和药代动力学的I期研究

目的：XTR003是一种新型的18f标记脂肪酸PET示踪剂，用于成像心肌脂肪酸代谢，可潜在地用于评估缺血性心脏病的心肌活力。该I期研究评估了其安全性、生物分布、辐射剂量学和药代动力学。方法：10名健康的中国志愿者（平均年龄28.4±4.6岁，女性3名）静息时静脉注射XTR003 (296 ~ 370 MBq)，监测注射当日及随访日的不良事件。290分钟内获得多张全身PET图像，并进行处理以研究生物分布和辐射剂量学。同时采集全血、血浆和尿液420分钟，用放射性测量评价药代动力学。结果：仅发生2例治疗相关不良事件，无严重不良反应。注射示踪剂后，血浆中XTR003在2.883 min达到峰值，占每克注射剂量的0.0108235 % (%ID/g)，在30 min时降至最低。0-20 min全身PET图像显示，心脏和肝脏是注射剂量百分比（%ID）最高的两个关键器官（4.37±0.66和48.76±4.17% ID）。具体来说，XTR003在心脏中表现出高的初始摄取，持续保留时间长达290分钟（SUV: 0-20分钟6.50±2.54,270-290分钟5.89±2.18）。全身有效辐射剂量为17μSv/MBq。累计尿排泄率为9.009%。结论：XTR003作为18f标记的放射性示踪剂，安全性好，耐受性好。XTR003在心脏中的快速吸收和长时间滞留为评估心肌脂肪酸代谢提供了希望。探索XTR003检测心肌活力功效的II期临床试验是有必要的。试验注册号：ClinicalTrials.gov标识符：NCT05136391。

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来源期刊

Journal of Nuclear Cardiology 医学-核医学

CiteScore

5.30

自引率

20.80%

发文量

249

审稿时长

4-8 weeks

期刊介绍： 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.