A Phase I-II, Open-Label, Multicenter Trial to Determine the Dosimetry and Safety of Tc-99m-Sestamibi in Pediatric Subjects

作者：Azarbar Sayena; Salardini Arash; Dahdah Nagib^*; Lazewatsky Joel; Sparks Richard; Portman Michael; Crane Paul D; Lee Meng Luen; Zhu Qi

来源：Journal of Nuclear Medicine, 2015, 56(5): 728-736.

DOI：10.2967/jnumed.114.146795

• myocardial nuclear imaging
• safety
• pharmacokinetics
• children

Myocardial perfusion imaging has long been used off label by practitioners attending for children with cardiac aliments. To provide clinicians with evidence-based dosage recommendation, a phase I-II, open-label, nonrandomized, multicenter trial was therefore designed using Tc-99m-sestamibi in pediatric subjects (registered under www. clinicaltrials. gov identifier no. NCT00162045). Methods: Safety and pharmacokinetic data were collected from 78 subjects using either a 1-d imaging protocol (3.7-7.4 MBq/kg, followed by 11.1 MBq/kg) or a 2-d protocol (7.4 MBq/kg for both rest and stress). Anterior and posterior planar images were collected at 15min, 1.5 h, 4 h, and 8 h. Blood and urine samples were collected at predetermined times. Results: Subjects included 39 children (mean age +/- SD, 8.5 +/- 2.04 y) and 39 adolescents (mean age +/- SD, 13.6 +/- 1.39 y). Mean estimated organ-absorbed doses to the upper large intestine, small intestine, gallbladder wall, and lower large intestines were 0.082, 0.043, 0.042, and 0.035 mSv/MBq, respectively. All patients tolerated the radiotracer without serious adverse effects. Significant differences were observed in the liver, upper large intestine contents, and small intestine contents between rest and stress imaging. The effective dose equivalent and effective dose averages were lower in adolescents than younger children (0.011 and 0.019 mSv/MBq, respectively; P < 0.0001). Percentage injected doses (% IDs) corrected for radioactive decay in all dosimetry-evaluable subjects at 15min and 4 h were 1.9% and 1.2% in themyocardium. Similarly in the lungs, the% ID for all dosimetryevaluable subjects was 4.9% at 15 min after injection. At rest, the % ID in the liver decreased from a maximum of about 26% at 15 min to less than 9% at 90 min. With stress, values decreased from 15% to 7%, respectively. Conclusion: The estimates of radiation dosimetry, pharmacokinetic parameters, and safety profile in this study population are similar to published studies based on body-mass extrapolations from studies in adults. As such, applying current Tc-99m-sestamibi dosing regimens for 1- and 2-d protocols based on those extrapolations will result in the expected radiation dose in children and adolescents.

• 出版日期2015-5-1