Schmitz Jennifer, Schwab Julian, Schwenck Johannes, Chen Qian, Quintanilla-Martinez Leticia, Hahn Markus, Wietek Beate, Schwenzer Nina, Staebler Annette, Kohlhofer Ursula, Aina Olulanu H, Hubbard Neil E, Reischl Gerald, Borowsky Alexander D, Brucker Sara, Nikolaou Konstantin, la Fougère Christian, Cardiff Robert D, Pichler Bernd J, Schmid Andreas M
Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany. Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University Tuebingen, Tuebingen, Germany.
Cancer Res. 2016 Sep 15;76(18):5512-22. doi: 10.1158/0008-5472.CAN-15-0642. Epub 2016 Jul 27.
Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [(18)F]Fluorodeoxyglucose ([(18)F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [(18)F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512-22. ©2016 AACR.
异质性乳腺肿瘤的鉴别诊断和治疗是一项重大的临床挑战。为了满足在体内定义肿瘤分子和功能特征的全面、非侵入性策略的需求，我们在乳腺癌的多瘤病毒中T抗原转基因小鼠模型中研究了代谢PET和扩散加权（DW）-MRI的新型组合。在该模型中对肿瘤内和肿瘤间异质性聚类进行体素分析，产生了基于[（18）F]氟脱氧葡萄糖（[（18）F]FDG）-PET和DW-MRI的多参数特征，其在体内识别出三种不同的肿瘤表型，包括实性腺泡、实性结节性恶性肿瘤以及囊性增生。为了评估这种方法用于临床的可行性，我们在同步PET/MRI系统中使用DW-MRI和[（18）F]FDG-PET检查了5例患者的雌激素受体阳性和孕激素受体阳性乳腺肿瘤。术后体内PET/MRI数据与使用后一种传统诊断标准来定义表型的全切片组织学相关。通过这种方法，我们展示了如何同时非侵入性地获得分子、结构（微观、解剖）和功能信息，以识别异质性肿瘤内的癌前和恶性亚型。结合自动化分析，我们的结果表明多参数分子和功能成像可能能够为非侵入性癌症诊断提供全面的肿瘤分析。癌症研究；76（18）；5512 - 22。©2016美国癌症研究协会。
