Background <p>The North American consensus guidelines recommend a weight-based administered activity for renal cortical scintigraphy with ^99mTc-dimercaptosuccinic acid (DMSA; 1.85 MBq/kg or 0.05 mCi/kg). Patients weighing less than 10 kg are recommended to receive a minimum administered activity of 18.5 MBq (0.5 mCi), irrespective of their weight. This approach is presumably to provide sufficient counts for adequate image quality, but it has not been rigorously evaluated.</p> Objective <p>To compare the adequacy of image quality of infant DMSA renal SPECT examinations obtained using the minimum administered activity recommended by the consensus guidelines with simulated data utilizing a strict weight-based dosage.</p> Materials and methods <p><i>Phase 1</i>: Datasets of 55 infants (29 females, 26 males, median age 3.0 months and weight 5.6 kg) undergoing DMSA SPECT from 2016 to 2021 were identified with 7 used for training and 48 used for study analysis. Data from patients receiving the administered activity recommended by the consensus guidelines (“full dosage”, group A) were processed using binomial resampling to add Poisson noise to mimic a strict weight-based scheme (“simulated reduced dosage”, group A′). Three experienced nuclear medicine physicians, who were blinded to group membership and clinical information, independently evaluated adequacy of image quality for clinical interpretation on a 4-point scale. Student’s paired <i>t</i>-test was utilized for group comparisons and inter-rater agreements were calculated using kappa statistics. <i>Phase 2</i>: Group A′ simulated data were compared to a second cohort of ^99mTc-DMSA SPECT cases where the administered activity followed a strict weight-based regime (“true reduced dosage”, group B). Subjects weighing between 4-7 kg were selected (group A′, 10 patients, 4 females, 6 males, median age 3.00 months and weight 5.35 kg) to compare with similar-weight group B subjects (10 patients, 5 females, 5 males, median age 2.50 months and weight 6.05 kg). The same observers and 4-point scale from phase 1 were used. The Wilcoxon rank sum test was utilized for analysis.</p> Results <p>Observers’ ratings were combined for analysis resulting in <i>n</i>=144 case-pairs (3 observers × 48 case-pairs) in phase 1. In phase 1, the ratings of groups A and A′ were identical for 73.6% (106/144) of case-pairs and never differed by more than ±1 level. No significant rating difference was found between the groups (mean (SD) of 1.17 (0.93) versus 1.22 (0.98), <i>P</i>=0.20). Similarly, in phase 2, no significant rating difference was found between groups A′ and B (mean (SD) of 0.80 (0.81) versus 0.50 (0.68), <i>P</i>=0.14).</p> Conclusion <p>There was no significant difference in the adequacy of image quality of ^99mTc-DMSA SPECT examinations using a strict weight-based dosage compared to using the recommended minimum dosage for infants as small as 3 kg.</p> Graphical Abstract <p></p>