Abstract

BackgroundThe purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab.MethodsPET was performed on five patients with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the injection of approximately 130 MBq of the probe 64Cu-DOTA-trastuzumab. Radioactivity in metastatic brain tumors was evaluated based on PET images in five patients. Autoradiography, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one surgical case to confirm HER2 specificity of 64Cu-DOTA-trastuzumab.ResultsMetastatic brain lesions could be visualized by 64Cu-DOTA-trastuzumab PET in all of five cases, which might indicated that trastuzumab passes through the blood-brain barrier (BBB). The HER2 specificity of 64Cu-DOTA-trastuzumab was demonstrated in one patient by autoradiography, immunohistochemistry, and LC-MS/MS.ConclusionsCu-DOTA-trastuzumab PET could be a potential noninvasive procedure for serial identification of metastatic brain lesions in patients with HER2-positive breast cancer.Trial registrationUMIN000004170

Highlights

  • The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with 64Cu-1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab

  • We reported the production of 64Culabeled trastuzumab, 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab and that 64Cu-DOTA-trastuzumab PET imaging could detect primary HER2-positive breast cancer and metastatic lesions [10]

  • We demonstrated that 64Cu-DOTA-trastuzumab PET imaging could visualize metastatic brain lesions and confirmed the HER2 specificity of 64CuDOTA-trastuzumab by means of autoradiography, IHC, and liquid chromatography-tandem mass spectrometry (LC-MS/MS)

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Summary

Introduction

The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with 64Cu-1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab. It is important to examine HER2 expression in primary tumor and metastatic sites to determine whether anti-HER2 therapy is indicated. We reported the production of 64Culabeled trastuzumab, 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab and that 64Cu-DOTA-trastuzumab PET imaging could detect primary HER2-positive breast cancer and metastatic lesions [10]. This imaging technique can be used to serially

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