skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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. 2016. "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 = 2016,
month = 6
}
  • Purpose: Stereotactic body radiation therapy (SBRT) is increasingly being used to treat thoracic tumors. We attempted here to identify dose-volume parameters that predict chest wall toxicity (pain and skin reactions) in patients receiving thoracic SBRT. Patients and Methods: We screened a database of patients treated with SBRT between August 2004 and August 2008 to find patients with pulmonary tumors within 2.5 cm of the chest wall. All patients received a total dose of 50 Gy in four daily 12.5-Gy fractions. Toxicity was scored according to the NCI-CTCAE V3.0. Results: Of 360 patients in the database, 265 (268 tumors) had tumorsmore » within <2.5 cm of the chest wall; 104 (39%) developed skin toxicity (any grade); 14 (5%) developed acute pain (any grade), and 45 (17%) developed chronic pain (Grade 1 in 22 cases [49%] and Grade 2 or 3 in 23 cases [51%]). Both skin toxicity and chest wall pain were associated with the V{sub 30}, or volume of the chest wall receiving 30 Gy. Body mass index (BMI) was also strongly associated with the development of chest pain: patients with BMI {>=}29 had almost twice the risk of chronic pain (p = 0.03). Among patients with BMI >29, diabetes mellitus was a significant contributing factor to the development of chest pain. Conclusion: Safe use of SBRT with 50 Gy in four fractions for lesions close to the chest wall requires consideration of the chest wall volume receiving 30 Gy and the patient's BMI and diabetic state.« less
  • The purpose was, by means of a multicenter, prospective randomized, placebo-controlled study, to assess the impact of adding the radiation-enhancing agent lonidamine to standard {open_quotes}curative-intent{close_quotes} radiation therapy upon overall survival, progression-free survival, and local progression-free survival of patients with clinically localized but nonresectable nonsmall cell lung cancer. Lonidamine, or the lonidamine-placebo, was administered at a dose of 265 mg/m{sup 2} in three divided daily doses. Drug therapy began 2 days prior to the initiation of radiation therapy and continued until progression of disease mandated a change in therapy. The radiation therapy dose was 55-60 Gy, at a daily dose ofmore » 1.8 Gy and five treatments per week. Patients with clinical Stage II or III nonsmall cell lung cancer were stratified within the treatment center, and within two histologic strata: epidermoid vs. other nonsmall cell cancers. A total of 310 patients were enlisted on study, 152 on the placebo arm and 158 on the lonidamine arm. The median survival durations were 326 and 392 days for the placebo and lonidamine-treated groups respectively, p = 0.41 for a comparison of the survival curves. Median progression-free survival and median local progression-free survival durations were 197 days and 341 days for placebo + radiation therapy vs. 230 days and 300 days for lonidamine + radiation therapy; p-values for the respective curves were 0.75 and 0.42. Although there were proportionately more lonidamine-treated patients than placebo-treated patients demonstrating continued local control in excess of 12 months, the numbers of patients still at risk after 24 months were too small for meaningful statistical analysis. This multicenter Phase III study failed to demonstrate a significant advantage in the lonidamine-treated population in overall patient survival, in progression-free survival, or in the median duration of local control. 25 refs., 3 figs., 3 tabs.« less
  • We present this preliminary investigation into the safety and feasibility of endovascular therapy for morbid obesity in a swine model. A flow-limiting, balloon-expandable covered stent was placed in the superior mesenteric artery of three Yorkshire swine after femoral arterial cutdown. The pigs were monitored for between 15 and 51 days after the procedure and then killed, with weights obtained at 2-week increments. In the two pigs in which the stent was flow limiting, a reduced rate of weight gain (0.42 and 0.53 kg/day) was observed relative to the third pig (0.69 kg/day), associated with temporary food aversion and signs ofmore » mesenteric ischemia in one pig.« less
  • A registry established by the Radiation Therapy Oncology Group provides data for assessing the impact of clinical heating in a set of non-randomized patients treated with hyperthermia in participating member institutions from 1/77 to 6/81. This analysis focuses on tumor response when localized hyperthermia is produced by microwave and applied pursuant to two distinctly different treatment schedules. Hyperthermia treatments were biweekly and combined with daily radiation treatments in one patient group, and combined with biweekly radiation treatment in another. None of the patients received concurrent chemotherapy; all received between 3 and 13 hyperthermia treatments; all had superficial, measurable tumors. Generally,more » the two treatment schedules achieved similar levels of tumor response. Adenocarcinoma and squamous cell carcinoma in both samples responded well to these combined treatments. Best responses to treatment generally occurred between 28 and 84 days after completion of the combined therapy course. There were no differences between the two samples with respect to median days to best response or response duration. Blister, ulcer or wet desquamation were reported as the maximum skin reaction. No correlation could be found, however, between reported worst skin reaction and therapy characteristics including maximum skin temperature, maximum tumor temperature, total minutes of heat and total radiation dose.« less
  • Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growthmore » factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.« less