Anna G Sorace1, Anum K Syed2, Stephanie L Barnes2,3, C Chad Quarles4, Violeta Sanchez5, Hakmook Kang6, Thomas E Yankeelov7,2,3. 1. Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, 1912 Speedway, Austin, TX, 78712, USA. anna.sorace@austin.utexas.edu. 2. Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA. 3. Institute for Computational and Engineering Sciences, The University of Texas at Austin, Austin, TX, USA. 4. Division of Imaging Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. 5. Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA. 6. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA. 7. Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, 1912 Speedway, Austin, TX, 78712, USA.
Abstract
PURPOSE: Evaluation of [18F]fluoromisonidazole ([18F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer. PROCEDURES: Mice with BT474, HER2+ tumors, were imaged with [18F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging. RESULTS: [18F]FMISO-PET indicated significant decreases in hypoxia beginning on day 3 (P < 0.01) prior to changes in tumor size. These results were confirmed with pimonidazole staining on day 7 (P < 0.01); additionally, there was a significant positive linear correlation between histology and PET imaging (r 2 = 0.85). CONCLUSIONS: [18F]FMISO-PET is a clinically relevant modality which provides the opportunity to (1) predict response to HER2+ therapy before changes in tumor size and (2) identify decreases in hypoxia which has the potential to guide subsequent therapy.
PURPOSE: Evaluation of [18F]fluoromisonidazole ([18F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer. PROCEDURES: Mice with BT474, HER2+ tumors, were imaged with [18F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging. RESULTS: [18F]FMISO-PET indicated significant decreases in hypoxia beginning on day 3 (P < 0.01) prior to changes in tumor size. These results were confirmed with pimonidazole staining on day 7 (P < 0.01); additionally, there was a significant positive linear correlation between histology and PET imaging (r 2 = 0.85). CONCLUSIONS: [18F]FMISO-PET is a clinically relevant modality which provides the opportunity to (1) predict response to HER2+ therapy before changes in tumor size and (2) identify decreases in hypoxia which has the potential to guide subsequent therapy.
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