Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2025
Preclinical and first-in-human studies of a novel tracer for single-photon emission computed tomography myocardial blood flow quantification.
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Gu Yufan, Sun Ruoxi, Ren Wanjie, Xi Xiaoying, Han Kai, Zhang Zongyao, Liu Shuang, Fang Wei, Wang Lei
Аннотация
BACKGROUND: This study aimed to develop a dedicated tracer with high first-pass extraction fraction and stable heart retention for single-photon emission computed tomography (SPECT) myocardial perfusion imaging and flow measurement.
METHODS: Three 99mTc-labeled compounds (99mTc-4BOH, 99mTc-3BOH, and 99mTc-2BOH) were evaluated by mouse ex vivo distribution and swine planar imaging studies. 99mTc-4BOH was identified as a candidate and compared with 99mTc-Teboroxime and 99mTc-Sestamibi in swine on cadmium zinc telluride SPECT to study organ uptake and kinetic properties. Head-to-head comparisons of 99mTc-4BOH with 99mTc-Sestamibi and 13N-NH3 were performed on two separate pilot cohorts each comprising 10 patients.
RESULTS: The myocardial uptake of 99mTc-4BOH demonstrated significantly higher levels than 99mTc-Sestamibi in swine and human, evidenced by higher K1 values (swine rest: .81 ± .03 mL/g/min vs .43 ± .09 mL/g/min, P < .001; stress: 1.19 ± .26 mL/g/min vs .50 ± .10 mL/g/min, P < .001; human rest: .74 ± .09 mL/g/min vs .38 ± .04 mL/g/min, P < .001; stress 1.42 ± .17 mL/g/min vs .59 ± .07 mL/g/min, P < .001). k2 values of 99mTc-4BOH were lower than those of 99mTc-Teboroxime (rest: .18 ± .03/min vs .26 ± .01/min, P < .001; stress: .26 ± .04/min vs .38 ± .08/min, P < .01), suggesting greater stability than 99mTc-Teboroxime in the swine. Three- to 8-min data after injection are sufficient to produce high-quality perfusion images that offer clear visualization of the myocardium and minimal interference artifacts due to favorable heart-to-liver ratios of 99mTc-4BOH. Furthermore, K1 values from 99mTc-4BOH SPECT significantly correlated with 13N-NH3 positron emission tomography myocardial blood flow (MBF) (ρ = .83 on per-patient level, P < .001; ρ = .81 on per-vessel level, P < .001).
CONCLUSIONS: 99mTc-4BOH exhibited an encouraging pharmacokinetic profile with high and relatively stable cardiac uptake. It constitutes a promising candidate as myocardial perfusion radiotracer for SPECT MBF quantification.
METHODS: Three 99mTc-labeled compounds (99mTc-4BOH, 99mTc-3BOH, and 99mTc-2BOH) were evaluated by mouse ex vivo distribution and swine planar imaging studies. 99mTc-4BOH was identified as a candidate and compared with 99mTc-Teboroxime and 99mTc-Sestamibi in swine on cadmium zinc telluride SPECT to study organ uptake and kinetic properties. Head-to-head comparisons of 99mTc-4BOH with 99mTc-Sestamibi and 13N-NH3 were performed on two separate pilot cohorts each comprising 10 patients.
RESULTS: The myocardial uptake of 99mTc-4BOH demonstrated significantly higher levels than 99mTc-Sestamibi in swine and human, evidenced by higher K1 values (swine rest: .81 ± .03 mL/g/min vs .43 ± .09 mL/g/min, P < .001; stress: 1.19 ± .26 mL/g/min vs .50 ± .10 mL/g/min, P < .001; human rest: .74 ± .09 mL/g/min vs .38 ± .04 mL/g/min, P < .001; stress 1.42 ± .17 mL/g/min vs .59 ± .07 mL/g/min, P < .001). k2 values of 99mTc-4BOH were lower than those of 99mTc-Teboroxime (rest: .18 ± .03/min vs .26 ± .01/min, P < .001; stress: .26 ± .04/min vs .38 ± .08/min, P < .01), suggesting greater stability than 99mTc-Teboroxime in the swine. Three- to 8-min data after injection are sufficient to produce high-quality perfusion images that offer clear visualization of the myocardium and minimal interference artifacts due to favorable heart-to-liver ratios of 99mTc-4BOH. Furthermore, K1 values from 99mTc-4BOH SPECT significantly correlated with 13N-NH3 positron emission tomography myocardial blood flow (MBF) (ρ = .83 on per-patient level, P < .001; ρ = .81 on per-vessel level, P < .001).
CONCLUSIONS: 99mTc-4BOH exhibited an encouraging pharmacokinetic profile with high and relatively stable cardiac uptake. It constitutes a promising candidate as myocardial perfusion radiotracer for SPECT MBF quantification.