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Title: Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts

Abstract

Purpose: The purpose of this study was to investigate the effect of α-particle-emitting {sup 227}Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of {sup 227}Th-trastuzumab. Methods and Materials: Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm{sup 3} (mean ± SEM) were treated with a single injection of either {sup 227}Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study the effect of {sup 227}Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Results: Significant increases of k{sub ep}, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and k{sub el,} the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared withmore » the control group. The product of k{sub ep} and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Conclusions: Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after {sup 227}Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital, Oslo (Norway)
  2. Department of Oncology, Division of Medicine, Akershus University Hospital, Lørenskog (Norway)
  3. Department of Research and Development, Algeta ASA, Oslo (Norway)
  4. Nordic Nanovector AS, Oslo (Norway)
Publication Date:
OSTI Identifier:
22267867
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 87; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; KILO BQ RANGE 100-1000; MICE; NEOPLASMS; NMR IMAGING; OVARIES; RADIATION DOSES; RADIOIMMUNOTHERAPY; THORIUM 227

Citation Formats

Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no, Røe, Kathrine, Brevik, Ellen Mengshoel, and Dahle, Jostein. Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts. United States: N. p., 2013. Web. doi:10.1016/J.IJROBP.2013.04.052.
Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no, Røe, Kathrine, Brevik, Ellen Mengshoel, & Dahle, Jostein. Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts. United States. doi:10.1016/J.IJROBP.2013.04.052.
Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no, Røe, Kathrine, Brevik, Ellen Mengshoel, and Dahle, Jostein. Sun . "Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts". United States. doi:10.1016/J.IJROBP.2013.04.052.
@article{osti_22267867,
title = {Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts},
author = {Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no and Røe, Kathrine and Brevik, Ellen Mengshoel and Dahle, Jostein},
abstractNote = {Purpose: The purpose of this study was to investigate the effect of α-particle-emitting {sup 227}Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of {sup 227}Th-trastuzumab. Methods and Materials: Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm{sup 3} (mean ± SEM) were treated with a single injection of either {sup 227}Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study the effect of {sup 227}Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Results: Significant increases of k{sub ep}, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and k{sub el,} the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared with the control group. The product of k{sub ep} and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Conclusions: Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after {sup 227}Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts.},
doi = {10.1016/J.IJROBP.2013.04.052},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 1,
volume = 87,
place = {United States},
year = {2013},
month = {9}
}