Abstract
To characterize the effect of the number of Y90 microspheres on the microscopic dosimetry and absorbed-dose uniformity in a porcine model. Four healthy pigs received lobar infusions of Y90 glass microspheres at 4, 8, 12 and 16 days post-calibration. The administration dates resulted in the specific activity per microsphere of approximately 855, 302, 106, and 38 Bq at 4, 8, 12 and 16 days, respectively. CBCT was used to evaluate the perfused tissue volume at the time of delivery and the activity was selected to deliver a consistent absorbed dose of 50-60 Gy. After a 1 month survival, livers were explanted, fixed in formalin and gross pathologic evaluation performed. The embolized lobes were scanned on a Bruker MicroCT with a 9 um3 resolution. A blob-detection algorithm was used to identify all microspheres and a complete microdosimetric evaluation was performed. Twelve and 16-day pigs demonstrated focally distributed areas of necrosis on gross exam at organ harvest. Average lobar absorbed-doses were 50.9, 48.7, 53.5 and 50.0 Gy in the 4, 8, 12 and 16 day pigs, as calculated based on MicroCT identification of individual spheres. 3D analysis of microsphere deposition patterns showed average number of microspheres per cluster was 2.3, 3.4, 5.8 and 8.6 in 4, 8, 12 and 16 day pigs, with 4%, 7%, 11% and 14% of clusters in each pig containing >10 spheres, respectively. The percentage of liver tissue receiving more than 40Gy was 32%, 47%, 52% and 58% (days 4, 8, 12, 16), suggesting that microsphere number increases the fraction of normal tissue receiving a higher absorbed dose (p<.01). An analysis of absorbed dose to individual lobules shows higher maximum lobular dose (3501 Gy) in the 4 day pig compared to the 12 day pig (766 Gy, p<.01), but with lower median lobular dose in the 4 day pig (23 Gy) vs the 12 day pig (40 Gy, p<.01). While average organ doses were comparable, earlier treatments (i.e., 4 days post calibration) resulted in a greater fraction of liver receiving lower absorbed-doses (<40 Gy) compared to treatments at 12 or 16 days post calibration. These data suggest that treatments closer to calibration (higher specific activity/sphere) may be less hepatotoxic.
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