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 6 2.2 (standard error of the mean) was significantly greater than the 111 In-trastuzumab uptake of 13.6% ID/g 6 1.0 and the 125 Ipanitumumab uptake of 7.4% ID/g 6 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.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

Heparan sulfate chains contribute to the anticoagulant milieu in malignant pleural effusion

“…Mouse breast cancer 10 4 cells (EMT-6) were injected to the intrapleural cavity of BALB/c mice, as previously described 20. Heparanase inhibitory peptide 615 was injected subcutaneously on alternate days, in the area opposite to the tumour side, starting on the first day after the tumour cell injection.…”

Diagnosis and Treatment of Malignant Pleural Mesothelioma

“…[87][88][89] Highly sensitive probes combined with biofluorescent techniques that can detect tumors in animal models have been developed. 90,91 Techniques based on labeled antibodies or nanoparticles with nuclear magnetic resonance are available, 92,93 and the prospect of eventually using these in humans is good. Until such time, however, it seems more realistic to concentrate on the search for markers that are detectable in peripheral blood and sufficiently sensitive and specific for the diagnosis of malignant mesothelioma.…”

The Biology of Malignant Mesothelioma and the Relevance of Preclinical Models

“…Both cell and mouse models have been applied to test the efficiency of drugs in mono-or multimodality chemotherapies, immunotherapies and target therapies, oncovirotherapies, or cell and gene therapies. SPECT, single photon emission computed tomography; IPe, intra-pleural; Ipl: intra-peritoneal; PDX, patient-derived xenograft.epidermal growth factor receptor (HER) were visualized with single photon emission computed tomography (SPECT) and MRI in an orthotopic MM model with radiolabeled specific antibodies(59). Bioluminescence of luc-expressed MM remains the most common strategy to monitor tumor development in orthotopic models.…”