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Molecular Bioluminescence Imaging as a Noninvasive Tool for Monitoring Tumor Growth and Therapeutic Response to MRI-Guided Laser Ablation in a Rat Model of Hepatocellular Carcinoma

Thompson, Scott M. BA*; Callstrom, Matthew R. MD, PhD; Knudsen, Bruce E. MS; Anderson, Jill L. BA§; Sutor, Shari L. BA; Butters, Kim A. BA; Kuo, Chaincy PhD; Grande, Joseph P. MD, PhD; Roberts, Lewis R. MB, ChB, PhD#; Woodrum, David A. MD, PhD

doi: 10.1097/RLI.0b013e31827a4a3f
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Objectives The objective of this study was to quantitatively compare tumor imaging by magnetic resonance imaging (MRI) and molecular bioluminescence imaging (BLI) and test the feasibility of monitoring the effect of MRI-guided laser ablation on tumor viability by 2-dimensional BLI and 3-dimensional diffuse luminescence tomography (3D DLIT) in an orthotopic rat model of hepatocellular carcinoma.

Materials and Methods This study was approved by the animal care committee. Rats underwent injection of N1S1 cells stably transfected with an empty vector (n = 3) or a heat shock element luciferase reporter (HSE-luc; n = 4) into the liver. All rats underwent MRI to assess tumor establishment and volume and 2-dimensional BLI to assess tumor luminescence at day 7 with subsequent MRI and 2D BLI and 3D DLIT in select animals at days 14 and 21. Magnetic resonance imaging–guided laser ablation of the tumor was performed with preablation and postablation 2D BLI and/or 3D DLIT (n = 2). The tumors underwent histopathologic analysis to assess tumor viability.

Results The MRI scans demonstrated hyperintense T2-weighted lesions at 3 of 3 and 4 of 4 sites in the empty vector and HSE-luc rats, respectively. Two-dimensional BLI quantitation demonstrated 23.0-fold higher radiance in the HSE-luc group compared with the empty vector group at day 7 (P < 0.01) and a significant correlation with tumor volume by MRI (r = 0.86; P < 0.03). Tumor dimensions by 3D DLIT and MRI demonstrated good agreement. Three-dimensional DLIT quantitation demonstrated better agreement with thepercentage of nonviable tumor by histopathology than did 2D BLI quantitation after the MRI-guided laser ablation.

Conclusions Bioluminescence imaging is feasible as a noninvasive, quantitative tool for monitoring tumor growth and therapeutic response to thermal ablation in a rat model of hepatocellular carcinoma.

Supplemental digital content is available in the text.

From the *Medical Scientist Training Program, College of Medicine; Departments of †Radiology, ‡Laboratory Medicine and Pathology, §Physiology and Biomedical Engineering; ∥Division of Oncology Research, Mayo Clinic, Rochester, MN; ¶Caliper Life Sciences, a PerkinElmer Company, Alameda, CA; #Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.

Received for publication March 14, 2012; and accepted for publication, after revision, October 8, 2012.

Conflicts of interest and sources of funding: Infrastructure support was provided by construction grant NIH C06 RR018898 and Center for Translational Science Activities grant NIH UL1 RR024150 from the National Institutes of Health.

Research support provided in part by SIR Foundation Allied Scientist Training grant and RSNA Research Scholar grant.

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.investigativeradiology.com)

Reprints: Scott M. Thompson, BA, Medical Scientist Training Program, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: Thompson.scott@mayo.edu.

© 2013 by Lippincott Williams & Wilkins