Yttrium-90 Portal Vein Radioembolization in Sprague–Dawley Rats: Dose-Dependent Imaging and Pathological Changes in Normal Liver

Andrew C. Gordon, Sarah B. White, Vanessa L. Gates, Weiguo Li, Daniel Procissi, Zhuoli Zhang, Kathleen R. Harris, Dong Hyun Kim, Samdeep K. Mouli, Reed A. Omary, Riad Salem, Andrew C. Larson, Robert J. Lewandowski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: Portal vein embolization (PVE) is an established neoadjuvant method to induce future liver remnant hypertrophy prior to surgical resection of hepatic tumors. The purpose of our study was to examine the feasibility of PVE with glass 90Y microspheres (Y90 PVE) in Sprague–Dawley rats. We tested the hypothesis that increased doses of Y90 PVE would increase target lobe fibrosis and atrophy. Methods: Twenty-two rats were assigned to four groups for Y90 PVE to the right median lobe: very high- (273.8 MBq; n = 2), high- (99.9 MBq; n = 10), medium- (48.1 MBq; n = 5), and low-dose (14.8 MBq; n = 5). An untreated control group included seven rats. 90Y PET/CT of 90Y distributions confirmed lobar targeting. MRI volumes were measured at baseline, 2-, 4-, 8- and 12-weeks. Explanted hepatic lobes were weighed, sectioned, and stained for H&E and immunohistochemistry. Digitized slides allowed quantitative measurements of fibrosis (20 foci/slide). Results: Ex vivo measurements confirmed 91–97% activity was localized to the target lobe (n = 4). The percent growth of the target lobe relative to baseline was − 5.0% (95% CI − 17.0–6.9%) for high-, medium dose rats compared to + 18.6% (95% CI + 7.6–29.7%) in the low-dose group at 12-weeks (p = 0.0043). Radiation fibrosis increased in a dose-dependent fashion. Fibrotic area/microsphere was 22,893.5, 14,946.2 ± 2253.3, 15,304.5 ± 4716.6, and 5268.8 ± 2297.2 μm2 for very high- (n = 1), high- (n = 4), medium- (n = 3), and low-dose groups (n = 5), respectively. Conclusion: Y90 PVE was feasible in the rat model, resulted in target lobe atrophy, and dose-dependent increases in hepatic fibrosis at 12 weeks. The onset of imaging-based volumetric changes was 8–12 weeks.

Original languageEnglish (US)
Pages (from-to)1925-1935
Number of pages11
JournalCardiovascular and Interventional Radiology
Volume43
Issue number12
DOIs
StatePublished - Dec 1 2020

Keywords

  • Dosing
  • Fibrosis
  • Hepatic radioembolization
  • Magnetic resonance imaging
  • Portal vein embolization
  • Yttrium-90

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Yttrium-90 Portal Vein Radioembolization in Sprague–Dawley Rats: Dose-Dependent Imaging and Pathological Changes in Normal Liver'. Together they form a unique fingerprint.

Cite this