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Orthotopic pleural mesothelioma in mice: SPECT/CT and MR imaging with HER1- and HER2-targeted radiolabeled antibodies.

Abstract：

PURPOSE:To evaluate the potential of anti-human epidermal growth factor receptor (HER)1- and anti-HER2-targeted radiolabeled antibodies and magnetic resonance (MR) imaging for imaging of orthotopic malignant pleural mesothelioma (MPM) in mouse models. MATERIALS AND METHODS:Animal studies with 165 mice were performed in accordance with National Institutes of Health guidelines for the humane use of animals, and all procedures were approved by the institutional Animal Care and Use Committee. Flow cytometry studies were performed to evaluate HER1 and HER2 expression in NCI-H226 and MSTO-211H mesothelioma cells. Biodistribution and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies were performed in mice (four or five per group, depending on tumor growth) bearing subcutaneous and orthotopic MPM tumors by using HER1- and HER2-targeted indium 111 ((111)In)- and iodine 125 ((125)I)-labeled panitumumab and trastuzumab, respectively. Longitudinal MR imaging over 5 weeks was performed in three mice bearing orthotopic tumors to monitor tumor growth and metastases. SPECT/CT/MR imaging studies were performed at the final time point in the orthotopic models (n = 3). The standard unpaired Student t test was used to compare groups. RESULTS:Orthotopic tumors and pleural effusions were clearly visualized at MR imaging 3 weeks after tumor cell inoculation. At 2 days after injection, the mean (111)In-panitumumab uptake of 29.6% injected dose (ID) per gram ± 2.2 (standard error of the mean) was significantly greater than the (111)In-trastuzumab uptake of 13.6% ID/g ± 1.0 and the (125)I-panitumumab uptake of 7.4% ID/g ± 1.2 (P = .0006 and P = .0001, respectively). MR imaging fusion with SPECT/CT provided more accurate information about (111)In-panitumumab localization in the tumor, as the tumor was poorly visualized at CT alone. CONCLUSION:This study demonstrates the utility of radiolabeled anti-HER1 antibodies in the imaging of MPM in preclinical models. SUPPLEMENTAL MATERIAL:http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121021/-/DC1.

journal_name

Radiology

journal_title

Radiology

authors

Nayak TK,Bernardo M,Milenic DE,Choyke PL,Brechbiel MW

doi

10.1148/radiol.12121021

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

173-82

issue

eissn

0033-8419

issn

1527-1315

pii

radiol.12121021

journal_volume

267

pub_type

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Orthotopic pleural mesothelioma in mice: SPECT/CT and MR imaging with HER1- and HER2-targeted radiolabeled antibodies.