Determination of renal 99mTc-DMSA pharmacokinetics in pediatric patients: Implications for current dosing guidelines in pediatric imaging

153 Objectives: Currently available pediatric dose estimates for 99mTc-DMSA use pediatric S values with PK data derived from adults. As part of an ongoing dose-optimization effort, we have previously reported on the development of pharmacokinetic (PK) models for pediatric imaging agents. Further development of PK models depends on the availability of longitudinal imaging data in children, which are quite limited. Our preliminary models were based on ICRP 53 and recently-collected single-time-point imaging data from clinical studies at Boston Children’s Hospital (BCH). In this study we have measured the kidney uptake of the renal imaging agent 99mTc-DMSA in children, by supplementing the clinically acquired imaging data with images that are earlier or later so that each patient is imaged no more than twice. In young children, this approach is essential for acquiring otherwise unobtainable PK data. Methods: Twelve pediatric patients (age range: 11 months to 6 year-old) were enrolled in an IRB-approved imaging protocol at BCH. Routine SPECT imaging was performed at 2-3 h post-injection (p.i.) of 99mTc-DMSA. A planar image was also acquired at the clinical time-point for all patients immediately after the SPECT acquisition. A 2nd planar image was acquired between 15-90 min p.i. (8 patients, early group), or at 4-6 h p.i. (3 patients, delayed group). SPECT images were reconstructed iteratively with attenuation, scatter and collimator-detector response compensations. As CT images were not available, an attenuation map was generated from reconstructed scatter window data. The kidney activity was measured in the SPECT images and the percent injected activity (% IA) was calculated. Kidney activity was also measured in both planar images and corrected for scatter, background and attenuation. Kidney activity from SPECT was used in conjunction with the planar image at the clinical time-point to provide a factor to quantify the activity in the 2nd planar image. The extracted PK data are being used in PK model development and validation. Results: Mean decay corrected %IA in the kidneys at the clinical time (2.7 ± 0.3 h p.i.) from SPECT was 30 ± 5% (range: 20-36%). The planar images provided previously unavailable PK data for 99mTc-DMSA in children as early as 0.2 h and up to 5.8 h p.i. The %IA in the kidneys from both planar and SPECT data starts from 10% at 0.2 h p.i. and is consistent with an increasing uptake in the kidneys beyond the clinical time-point up to 70% at 5.8 h p.i. (Fig. 1). In comparison, the ICRP 53 model prediction of the fractional kidney uptake at 1 h half-time was 0.5, while the Smith et al. [1] model prediction for the mean maximum (max) kidney uptake fraction in children was 0.424 at mean time to max of 6.8 h p.i. Activity data are being extracted from both SPECT and planar images for other organs of interest such as urinary bladder, liver, spleen, lungs and heart using input data from an age, height and girth-matched pediatric phantom population reported in our previous study. Conclusions: Longitudinal imaging data in pediatric patients for imaging agents including 99mTc-DMSA have been severely lacking. However, such data are currently being collected and have been quantified using a combined (planar + SPECT) imaging method, despite the challenges posed by imaging children more than once on the same day and the inconvenience to families. This valuable preliminary PK data set is being used to develop a PK model for 99mTc-DMSA that will enable specification of administered activities for pediatric patients that provide diagnostically acceptable images using the lowest tissue absorbed doses. We anticipate that this work will lead to establishing pediatric dosing guidelines that further advance the objectives of the Image Gently campaign.References 1. Smith, T., et al., (1996). Radiation dosimetry of technetium-99m-DMSA in children. 1996; J Nuc Med., 37(8), 1336-42