| Literature DB >> 31835038 |
Chenchen Pan1, Oliver Schoppe2, Arnaldo Parra-Damas3, Ruiyao Cai1, Mihail Ivilinov Todorov4, Gabor Gondi5, Bettina von Neubeck5, Nuray Böğürcü-Seidel6, Sascha Seidel7, Katia Sleiman8, Christian Veltkamp8, Benjamin Förstera1, Hongcheng Mai1, Zhouyi Rong1, Omelyan Trompak6, Alireza Ghasemigharagoz3, Madita Alice Reimer3, Angel M Cuesta7, Javier Coronel9, Irmela Jeremias10, Dieter Saur8, Amparo Acker-Palmer7, Till Acker6, Boyan K Garvalov11, Bjoern Menze12, Reinhard Zeidler13, Ali Ertürk14.
Abstract
Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantification in 5 different metastatic cancer models including breast, lung, and pancreatic cancer with distinct organotropisms allowed us to systematically analyze features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in entire mice. DeepMACT can thus considerably improve the discovery of effective antibody-based therapeutics at the pre-clinical stage. VIDEO ABSTRACT.Entities:
Keywords: antibody; cancer; deep learning; drug targeting; imaging; light-sheet; metastasis; microscopy; tissue clearing; vDISCO
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Year: 2019 PMID: 31835038 DOI: 10.1016/j.cell.2019.11.013
Source DB: PubMed Journal: Cell ISSN: 0092-8674 Impact factor: 41.582