Biokinetics Study of Tc-99m DMSA in Pediatric Molecular Imaging
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | Any - 6 |
| Updated: | 2/14/2019 |
| Start Date: | October 31, 2017 |
| End Date: | March 31, 2021 |
Biokinetics Study of Tc-99m DMSA for Dose Reduction in Pediatric Molecular Imaging
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 4 radiopharmaceuticals
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 dimethylsuccinic acid (DMSA), 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.
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 4 radiopharmaceuticals
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 dimethylsuccinic acid (DMSA), 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.
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 4
radiopharmaceuticals 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 dimethylsuccinic acid (DMSA), a radiopharmaceutical
commonly used in children for renal cortical 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 1-6 years old will be enrolled. Routine imaging will be performed 3-4 h
post-administration (PA) with a dual-detector rotating gamma camera. In each age group, half
of the subjects will also be imaged between 30 and 90 min, post-administration. The 2nd half
will be imaged at 5-6 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.
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 4
radiopharmaceuticals 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 dimethylsuccinic acid (DMSA), a radiopharmaceutical
commonly used in children for renal cortical 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 1-6 years old will be enrolled. Routine imaging will be performed 3-4 h
post-administration (PA) with a dual-detector rotating gamma camera. In each age group, half
of the subjects will also be imaged between 30 and 90 min, post-administration. The 2nd half
will be imaged at 5-6 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.
Inclusion Criteria:
- All patients within the specified age ranges scheduled at Boston Children's Hospital
for a nuclear medicine study utilizing Tc-99m DMSA will be eligible to volunteer for
inclusion in this study. It is also essential that inclusion does not compromise the
potential of acquiring the clinically indicated image acquisition.
Exclusion Criteria:
- Inability to be imaged at the additional time point without the need for sedation or
anesthesia
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