Phase I, first-in-human study of XTR004, a novel 18F-labeled tracer for myocardial perfusion PET: biodistribution, radiation dosimetry, pharmacokinetics and safety after a single injection at rest

Abstract

Abstract Purpose: XTR004 is a novel 18F-labeled myocardial perfusion imaging tracer that can be clinically used to assess myocardial ischemia from coronary artery disease. This study aimed to evaluate imaging characteristics of XTR004 after a single injection at rest in humans. Methods: Eleven healthy subjects (man=8) received an intravenous injection of 239-290 MBq (6.5-7.8 mCi) XTR004 and imaged with nine whole-body positron emission tomography (PET) scans within 4.7 h. Collection of blood and urine samples was concurrently performed for 7.25 h. Image processing utilized 3D registered PET and CT images to derive %ID and then calculated the radiation dose using a Hermes workstation with the embedded OLINDA/EXM program. The radioactive count profile was measured for whole-blood, plasma, and urine to characterize pharmacokinetics with the metabolic correction. The safety profile was evaluated during the day of dosing and three follow-up visits, including physical examination, vital signs, laboratory tests and adverse event observation. Results: Myocardial uptake of XTR004 was rapid, high, and stable throughout the PET imaging period. In the 0-12 min PET images, the top five organs of %ID were liver (26.81±4.01), kidney (11.43±2.49), lung (6.75±1.76), myocardium (4.72±0.67) and spleen (3.1±0.84). Mean values of Cmax, Tmax, t1/2, and AUC0-last calculated by the non-compartment model in corrected plasma were 0.0013896 %ID/g, 2.543 min, 45.171 min, and 0.03314 min* (%ID/g), respectively. Whole-body effective dose per unit of injected activity was 0.0165 mSv/MBq. Cumulative urine excretion (Cum Ae) was 8.18%. Treatment‐related adverse events occurred in seven subjects (63.6%) and were overall reported as stimulated pain at the injection site. No severe adverse event was collected. Conclusions: XTR004 having a favorable safety profile with rapid, high, and stable myocardial uptake in humans demonstrated an excellent potential for PET MPI. Further exploration of XTR004 PET MPI to detect myocardial ischemia can be warranted. (A Study of XTR004 PET Radiotracer in Healthy Volunteers, ClinicalTrials.gov number NCT05195879.)