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Title: SU-C-204-07: Radiation Therapy as a Potential Treatment for Obesity: Initial Data from a Preclinical Investigation

Abstract

Purpose: To evaluate the feasibility of Yttrium-90 (90Y) radionuclide therapy as a potential treatment for obesity in a porcine model. As the only appetite-stimulating hormone, localized targeting of ghrelin-producing X/A cells in the fundus of the stomach using 90Y may reduce serum ghrelin levels and decrease hunger. Methods: Under approval of the University of Tennessee IACUC, 8 young female pigs aged 12–13 weeks and weighing 21.8–28.1 Kg were included in this study. Six animals underwent transfemoral angiography as part of a two-day procedure involving: (1) infusion of 99mTc-MAA, followed by nuclear scintigraphy and contrast-enhanced CT for treatment-planning and (2) administration of resin 90Y microspheres into the stomach fundus. Calibrated 90Y activities were infused into the main left gastric and the gastric artery arising from the splenic to yield predetermined fundal absorbed doses. Control animals underwent a sham procedure with saline and contrast. Weekly animal weight and serum ghrelin were measured along with post-euthanasia histologic analyses of mucosal integrity and ghrelin immunoreactive cell-density. Results: 90Y radioembolization was administered to six pigs in dosages from 46.3 to 105.1 MBq resulting in average fundal absorbed doses between 35.5 and 91.9 Gy. No animal showed any signs of pain or GI complication through themore » duration of the study. Ghrelin immunoreactive cell-density was significantly lower in treated vs. control animals in both the stomach fundus (13.5 vs 34.8, P < 0.05) and body (11.2 vs 19.8, P < 0.05). A trend towards decreased weight gain in treated animals as well as a decrease in explanted stomach volume was also noted. Conclusion: The safety and technical feasibility of radiation therapy using 90Y radioembolization as a potential treatment for obesity has been demonstrated at fundal absorbed doses over 90 Gy. Preliminary data is suggestive of short-term safety and potential efficacy, however, further animal studies are required. Project was funded by SIRTex medical ltd.« less

Authors:
; ; ; ; ;  [1]
  1. University of Tennessee Medical Center, Knoxville, TN (United States)
Publication Date:
OSTI Identifier:
22624305
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
61 RADIATION PROTECTION AND DOSIMETRY; 60 APPLIED LIFE SCIENCES; ABSORBED RADIATION DOSES; ARTERIES; BIOMEDICAL RADIOGRAPHY; COMPUTERIZED TOMOGRAPHY; METABOLIC DISEASES; RADIOEMBOLIZATION; SAFETY; SCINTISCANNING; STOMACH; SWINE; TECHNETIUM 99; YTTRIUM 90

Citation Formats

Pasciak, A, Bradley, Y, Nodit, L, Bourgeois, A, Paxton, B, and Arepally, A. SU-C-204-07: Radiation Therapy as a Potential Treatment for Obesity: Initial Data from a Preclinical Investigation. United States: N. p., 2016. Web. doi:10.1118/1.4955540.
Pasciak, A, Bradley, Y, Nodit, L, Bourgeois, A, Paxton, B, & Arepally, A. SU-C-204-07: Radiation Therapy as a Potential Treatment for Obesity: Initial Data from a Preclinical Investigation. United States. doi:10.1118/1.4955540.
Pasciak, A, Bradley, Y, Nodit, L, Bourgeois, A, Paxton, B, and Arepally, A. Wed . "SU-C-204-07: Radiation Therapy as a Potential Treatment for Obesity: Initial Data from a Preclinical Investigation". United States. doi:10.1118/1.4955540.
@article{osti_22624305,
title = {SU-C-204-07: Radiation Therapy as a Potential Treatment for Obesity: Initial Data from a Preclinical Investigation},
author = {Pasciak, A and Bradley, Y and Nodit, L and Bourgeois, A and Paxton, B and Arepally, A},
abstractNote = {Purpose: To evaluate the feasibility of Yttrium-90 (90Y) radionuclide therapy as a potential treatment for obesity in a porcine model. As the only appetite-stimulating hormone, localized targeting of ghrelin-producing X/A cells in the fundus of the stomach using 90Y may reduce serum ghrelin levels and decrease hunger. Methods: Under approval of the University of Tennessee IACUC, 8 young female pigs aged 12–13 weeks and weighing 21.8–28.1 Kg were included in this study. Six animals underwent transfemoral angiography as part of a two-day procedure involving: (1) infusion of 99mTc-MAA, followed by nuclear scintigraphy and contrast-enhanced CT for treatment-planning and (2) administration of resin 90Y microspheres into the stomach fundus. Calibrated 90Y activities were infused into the main left gastric and the gastric artery arising from the splenic to yield predetermined fundal absorbed doses. Control animals underwent a sham procedure with saline and contrast. Weekly animal weight and serum ghrelin were measured along with post-euthanasia histologic analyses of mucosal integrity and ghrelin immunoreactive cell-density. Results: 90Y radioembolization was administered to six pigs in dosages from 46.3 to 105.1 MBq resulting in average fundal absorbed doses between 35.5 and 91.9 Gy. No animal showed any signs of pain or GI complication through the duration of the study. Ghrelin immunoreactive cell-density was significantly lower in treated vs. control animals in both the stomach fundus (13.5 vs 34.8, P < 0.05) and body (11.2 vs 19.8, P < 0.05). A trend towards decreased weight gain in treated animals as well as a decrease in explanted stomach volume was also noted. Conclusion: The safety and technical feasibility of radiation therapy using 90Y radioembolization as a potential treatment for obesity has been demonstrated at fundal absorbed doses over 90 Gy. Preliminary data is suggestive of short-term safety and potential efficacy, however, further animal studies are required. Project was funded by SIRTex medical ltd.},
doi = {10.1118/1.4955540},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}