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

J Nucl Med. 2015 May;56(5):728-36. doi: 10.2967/jnumed.114.146795. Epub 2015 Apr 9.

Abstract

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 (99m)Tc-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 15 min, 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 15 min and 4 h were 1.9% and 1.2% in the myocardium. Similarly in the lungs, the %ID for all dosimetry-evaluable 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 (99m)Tc-sestamibi dosing regimens for 1- and 2-d protocols based on those extrapolations will result in the expected radiation dose in children and adolescents.

Keywords: children; myocardial nuclear imaging; pharmacokinetics; safety.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Radiometry
  • Rest
  • Safety*
  • Stress, Physiological
  • Technetium Tc 99m Sestamibi / adverse effects*
  • Technetium Tc 99m Sestamibi / pharmacokinetics

Substances

  • Technetium Tc 99m Sestamibi

Associated data

  • ClinicalTrials.gov/NCT00162045