Biokinetics Study for Tc-99m MDP in Pediatric Molecular Imaging
Condition: Skeletal Injury
Study type: Observational

Summary: 
      The radiation exposure resulting from medical imaging is a topic of some concern. Nuclear
      medicine provides potentially life-saving information regarding physiological processes, and
      is of particular value in children where the rapid and unequivocal diagnosis of pathological
      concerns is essential for the health of these patients. The overall objective of this
      investigation is to optimize pediatric patient absorbed dose by keeping it as low as possible
      while maintaining excellent diagnostic quality of nuclear medicine images. This is
      particularly important since children are at increased risk due to the enhanced
      radiosensitivity of their tissues and the longer time-period over which radiation effects may
      manifest. Current dosimetric estimations in children are based on either animal biokinetic or
      pharmacokinetic data from adults due to paucity of data that exists for children. This
      situation will be improved through the following specific aims:

        -  Collect image-based pharmacokinetic (PK) data from patient volunteers in different age
           groups scheduled for routine nuclear medicine studies for Tc-99m methylene diphosphonate
           (MDP), a radiopharmaceutical commonly used in pediatric nuclear medicine

        -  Pool and analyze the data for different age groups for each radiopharmaceuticals and

        -  Generate biokinetic models to be used in subsequent dosimetric models for the
           optimization of pediatric nuclear medicine procedures.

      Since inadequate pharmacokinetic data currently exist in these patients, the investigators
      will use the data acquired in this study to establish PK models applicable to different age
      categories. Data on the pharmacokinetics of agents used in pediatric nuclear medicine are
      almost completely lacking. Internationally adopted dose coefficients (mSv/MBq) for pediatric
      nuclear medicine make age-dependent adjustments only for patient size and anatomical
      differences, while time-dependent kinetics from adult PK models are assumed due to the lack
      of kinetic data for children. The data obtained from this study will make it possible for the
      first time to determine how the PK in pediatric patients differs from adults. This will be
      done for Tc-99m MDP, a radiopharmaceutical commonly used for pediatric nuclear medicine
      imaging. The overall hope is that results will allow the molecular imaging community to
      implement pediatric dose-reduction approaches that substantially improve upon current
      guidelines pointing to future technological advances that could yield even greater
      dose-reduction while simultaneously improving diagnostic image quality.
    

Detailed description: 
      The overall objective of this investigation is to optimize pediatric patient absorbed dose by
      keeping it as low as possible while maintaining and even improving the diagnostic quality of
      nuclear medicine images. Current dosimetric estimations in children are based on either
      animal biokinetic or pharmacokinetic data from adults. This is due to paucity of data that
      exists specifically for children. This situation will be improved through the following
      specific aims:

        -  Collect imaging-based pharmacokinetic (PK) data from patient volunteers in different age
           groups scheduled for selected, routine nuclear medicine studies for Tc-99m methylene
           diphosphonate (MDP), a radiopharmaceutical commonly used in pediatric nuclear medicine

        -  Pool and analyze the data for different age groups for each radiopharmaceuticals and

        -  Generate biokinetic models to be used in subsequent dosimetric models for the
           optimization of pediatric nuclear medicine procedures.

      Pediatric absorbed dose estimates that are typically reported apply adult PK data with
      pediatric variations in body size and anatomy but not for differences in physiology between
      children and adults. Depending on the diagnostic agent, such differences can be of greater
      impact than anatomical differences. The investigators will acquire image data that will allow
      us to develop PK models for Tc-99m MDP, a radiopharmaceutical routinely used in pediatric
      nuclear medicine fr skeletal imaging. Patients undergoing standard of care imaging will be
      asked to consent to being imaged at one additional time point, either prior or subsequent to
      the time typical for clinical imaging. No patient will be asked to undergo more than one
      additional imaging time-point.

      It is important to note that the patient volunteers will not receive any additional radiation
      exposure for inclusion in this study. They are only being ask to allow imaging at an
      additional time point.

      Patients ages 1-16 years old will be included. Routine imaging will be collected 3-4 h
      post-administration with a dual-detector rotating gamma camera. Half of the subjects will
      also be imaged between 30 and 90 min, PA. The 2nd half will be at 4-6 h, post-administration.

      The additional imaging will occur on the day of the clinically indicated procedure. Other
      than that, there is no timeline associated with this study.

      Image data acquired from the subjects will be analyzed by the principle investigator and by
      colleagues at Johns Hopkins University and the University of Florida. Regions of interest
      will be defined around pertinent target organs and tissues and the count data recorded. The
      specific target organs will depend on the particular radiopharmaceutical. The data for each
      age range and time point will be pooled, normalized and fit to models describing the
      pharmacokinetics. The resultant models will be evaluated for age-based variations in the PK
      data and compared to existing, published models based on adult data to evaluated age based
      differences. Lastly, the impact that the more accurate PK has on dosimetric estimates of
      patients of different ages will be analyzed.

      The number of subjects required at each time point will be determined using nonlinear mixed
      effects modeling software to model the data and adjust for covariates. The likelihood ratio
      test based on the objective function value (OFV) will be used to estimate PK parameters for
      varying doses and ages using a Bayesian approach. The proposed sample size plan with subjects
      imaged at different time points is predicated on the Monte Carlo Mapped Power (MCMP) method
      to achieve 80% power for detecting age and dose effects and robust coverage in estimating
      individual PK parameters. It is expected that there will be 5-10 subjects per age group
      depending on the statistical requirements as described above.
    

Intervention name(s): Imaging Time
Intervention type(s): Drug
Intervention description(s): Participants will be asked to be imaged at an additional time point.
Observational model: Other
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        All patients within the specified age ranges scheduled at Boston Children's Hospital for a
        nuclear medicine study utilizing Tc-99m MDP will be eligible to volunteer for inclusion in
        this study.