{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:16:57Z","timestamp":1790079417920,"version":"4.0.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T00:00:00Z","timestamp":1478217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T00:00:00Z","timestamp":1478217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed at evaluating the reliability and precision of Diffuse Luminescent Imaging Tomography (DLIT) for monitoring primary tumor and metastatic spreading in breast cancer mice, and to develop a biomathematical model to describe the collected data. Using orthotopic mammary fat pad model of breast cancer (MDAMB231-Luc) in mice, we monitored tumor and metastatic spreading by three-dimensional (3D) bioluminescence and cross-validated it with standard bioluminescence imaging, caliper measurement and necropsy examination. DLIT imaging proved to be reproducible and reliable throughout time. It was possible to discriminate secondary lesions from the main breast cancer, without removing the primary tumor. Preferential metastatic sites were lungs, peritoneum and lymph nodes. Necropsy examinations confirmed DLIT measurements. Marked differences in growth profiles were observed, with an overestimation of the exponential phase when using a caliper as compared with bioluminescence. Our mathematical model taking into account the balance between living and necrotic cells proved to be able to reproduce the experimental data obtained with a caliper or DLIT imaging, because it could discriminate proliferative living cells from a more composite mass consisting of tumor cells, necrotic cell, or inflammatory tissues. DLIT imaging combined with mathematical modeling could be a powerful and informative tool in experimental oncology.<\/jats:p>","DOI":"10.1038\/srep36173","type":"journal-article","created":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T11:51:56Z","timestamp":1478260316000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["In Vivo Bioluminescence Tomography for Monitoring Breast Tumor Growth and Metastatic Spreading: Comparative Study and Mathematical Modeling"],"prefix":"10.1038","volume":"6","author":[{"given":"S\u00e9verine","family":"Mollard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphaelle","family":"Fanciullino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Giacometti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Serdjebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Benzekry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ciccolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,4]]},"reference":[{"key":"BFsrep36173_CR1","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1093\/annonc\/mdw022","volume":"27","author":"M Malvezzi","year":"2016","unstructured":"Malvezzi, M. et al. European cancer mortality predictions for the year 2016 with focus on leukaemias. Ann Oncol 27, 725\u2013731 (2016).","journal-title":"Ann Oncol"},{"key":"BFsrep36173_CR2","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.ctrv.2013.09.015","volume":"40","author":"E Senkus","year":"2014","unstructured":"Senkus, E., Cardoso, F. & Pagani, O. Time for more optimism in metastatic breast cancer? Cancer Treat Rev 40, 220\u2013228 (2014).","journal-title":"Cancer Treat Rev"},{"key":"BFsrep36173_CR3","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.breast.2015.03.001","volume":"24","author":"A Di Leo","year":"2015","unstructured":"Di Leo, A. et al. New approaches for improving outcomes in breast cancer in Europe. Breast 24, 321\u2013330 (2015).","journal-title":"Breast"},{"key":"BFsrep36173_CR4","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.cell.2006.11.001","volume":"127","author":"GP Gupta","year":"2006","unstructured":"Gupta, G. P. & Massague, J. Cancer metastasis: building a framework. Cell 127, 679\u2013695 (2006).","journal-title":"Cell"},{"key":"BFsrep36173_CR5","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.cell.2011.09.024","volume":"147","author":"S Valastyan","year":"2011","unstructured":"Valastyan, S. & Weinberg, R. A. Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275\u2013292 (2011).","journal-title":"Cell"},{"key":"BFsrep36173_CR6","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1476-4598-11-5","volume":"11","author":"K Augoff","year":"2012","unstructured":"Augoff, K., McCue, B., Plow, E. F. & Sossey-Alaoui, K. miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer. Mol Cancer 11, 5 (2012).","journal-title":"Mol Cancer"},{"key":"BFsrep36173_CR7","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/978-1-60761-058-8_13","volume":"602","author":"JE Talmadge","year":"2010","unstructured":"Talmadge, J. E. Models of metastasis in drug discovery. Methods Mol Biol 602, 215\u2013233 (2010).","journal-title":"Methods Mol Biol"},{"key":"BFsrep36173_CR8","doi-asserted-by":"publisher","first-page":"6397","DOI":"10.1158\/0008-5472.CAN-14-0721","volume":"74","author":"N Hartung","year":"2014","unstructured":"Hartung, N. et al. Mathematical modeling of tumor growth and metastatic spreading: validation in tumor-bearing mice. Cancer Res 74, 6397\u20136407 (2014).","journal-title":"Cancer Res"},{"key":"BFsrep36173_CR9","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.bbrc.2010.03.070","volume":"394","author":"IS Kim","year":"2010","unstructured":"Kim, I. S. & Baek, S. H. Mouse models for breast cancer metastasis. Biochem Biophys Res Commun 394, 443\u2013447 (2010).","journal-title":"Biochem Biophys Res Commun"},{"key":"BFsrep36173_CR10","doi-asserted-by":"publisher","first-page":"a003848","DOI":"10.1101\/cshperspect.a003848","volume":"2","author":"J Condeelis","year":"2010","unstructured":"Condeelis, J. & Weissleder, R. In vivo imaging in cancer. Cold Spring Harb Perspect Biol 2, a003848 (2010).","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"BFsrep36173_CR11","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1007\/s11307-012-0559-x","volume":"15","author":"T Poeschinger","year":"2013","unstructured":"Poeschinger, T., Renner, A., Weber, T. & Scheuer, W. Bioluminescence Imaging Correlates with Tumor Serum Marker, Organ Weights, Histology, and Human DNA Levels during Treatment of Orthotopic Tumor Xenografts with Antibodies. Mol Imaging Biol 15, 28\u201339 (2013).","journal-title":"Mol Imaging Biol"},{"key":"BFsrep36173_CR12","doi-asserted-by":"publisher","first-page":"504","DOI":"10.2174\/138920112799436258","volume":"13","author":"D Razansky","year":"2012","unstructured":"Razansky, D., Deliolanis, N. C., Vinegoni, C. & Ntziachristos, V. Deep tissue optical and optoacoustic molecular imaging technologies for pre-clinical research and drug discovery. Curr Pharm Biotechnol 13, 504\u2013522 (2012).","journal-title":"Curr Pharm Biotechnol"},{"key":"BFsrep36173_CR13","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s12038-011-9079-0","volume":"36","author":"P Ray","year":"2011","unstructured":"Ray, P. Multimodality molecular imaging of disease progression in living subjects. J Biosci 36, 499\u2013504 (2011).","journal-title":"J Biosci"},{"key":"BFsrep36173_CR14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.suronc.2010.07.008","volume":"21","author":"RA Madero-Visbal","year":"2012","unstructured":"Madero-Visbal, R. A. et al. Bioluminescence imaging correlates with tumor progression in an orthotopic mouse model of lung cancer. Surg Oncol 21, 23\u201329 (2012).","journal-title":"Surg Oncol"},{"key":"BFsrep36173_CR15","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1117\/1.1413210","volume":"6","author":"BW Rice","year":"2001","unstructured":"Rice, B. W., Cable, M. D. & Nelson, M. B. In vivo imaging of light-emitting probes. J Biomed Opt 6, 432\u2013440 (2001).","journal-title":"J Biomed Opt"},{"key":"BFsrep36173_CR16","doi-asserted-by":"publisher","first-page":"024007","DOI":"10.1117\/1.2717898","volume":"12","author":"C Kuo","year":"2007","unstructured":"Kuo, C., Coquoz, O., Troy, T. L., Xu, H. & Rice, B. W. Three-dimensional reconstruction of in vivo bioluminescent sources based on multispectral imaging. J Biomed Opt 12, 024007 (2007).","journal-title":"J Biomed Opt"},{"key":"BFsrep36173_CR17","doi-asserted-by":"publisher","first-page":"723","DOI":"10.2174\/1389201014666131226112507","volume":"14","author":"L Bu","year":"2013","unstructured":"Bu, L., Ma, X., Tu, Y., Shen, B. & Cheng, Z. Optical image-guided cancer therapy. Curr Pharm Biotechnol 14,723\u2013732 (2013).","journal-title":"Curr Pharm Biotechnol"},{"key":"BFsrep36173_CR18","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3389\/fonc.2016.00150","volume":"6","author":"T Xu","year":"2016","unstructured":"Xu, T., Close, D., Handagama, W., Marr, E., Sayler, G. & Ripp, S. The Expanding Toolbox of In Vivo Bioluminescent Imaging. Front Oncol 6, 150 (2016).","journal-title":"Front Oncol"},{"key":"BFsrep36173_CR19","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s11307-015-0864-2","volume":"18","author":"C Germain-Genevois","year":"2016","unstructured":"Germain-Genevois, C., Garandeau, O. & Couillaud, F. Detection of Brain Tumors and Systemic Metastases Using NanoLuc and Fluc for Dual Reporter Imaging. Mol Imaging Biol 18, 62\u201369 (2016).","journal-title":"Mol Imaging Biol"},{"key":"BFsrep36173_CR20","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1007\/s11307-010-0387-9","volume":"13","author":"S Pesnel","year":"2011","unstructured":"Pesnel, S. et al. Quantitation in bioluminescence imaging by correction of tissue absorption for experimental oncology. Mol Imaging Biol 13, 646\u2013652 (2011).","journal-title":"Mol Imaging Biol"},{"key":"BFsrep36173_CR21","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1364\/BOE.3.002131","volume":"3","author":"HR Basevi","year":"2012","unstructured":"Basevi, H. R. et al. Compressive sensing based reconstruction in bioluminescence tomography improves image resolution and robustness to noise. Biomed Opt Express 3, 2131\u20132141 (2012).","journal-title":"Biomed Opt Express"},{"key":"BFsrep36173_CR22","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.jconrel.2008.11.018","volume":"134","author":"T Mizuno","year":"2009","unstructured":"Mizuno, T., Mohri, K., Nasu, S., Danjo, K. & Okamoto, H. Dual imaging of pulmonary delivery and gene expression of dry powder inhalant by fluorescence and bioluminescence. J Control Release 134, 149\u2013154 (2009).","journal-title":"J Control Release"},{"key":"BFsrep36173_CR23","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/BF00391826","volume":"105","author":"G Carlsson","year":"1983","unstructured":"Carlsson, G., Gullberg, B. & Hafstrom, L. Estimation of liver tumor volume using different formulas - an experimental study in rats. J Cancer Res Clin Oncol 105, 20\u201323 (1983).","journal-title":"J Cancer Res Clin Oncol"},{"key":"BFsrep36173_CR24","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1158\/0008-5472.CAN-03-2524","volume":"64","author":"M Simeoni","year":"2004","unstructured":"Simeoni, M., Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cancer Res 64, 1094\u20131101 (2004).","journal-title":"Cancer Res"},{"key":"BFsrep36173_CR25","doi-asserted-by":"publisher","first-page":"e1003800","DOI":"10.1371\/journal.pcbi.1003800","volume":"10","author":"S Benzekry","year":"2014","unstructured":"Benzekry, S. et al. Classical mathematical models for description and prediction of experimental tumor growth. PLoS Computational Biology 10, e1003800 (2014).","journal-title":"PLoS Computational Biology"},{"key":"BFsrep36173_CR26","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1158\/0008-5472.CAN-15-1389","volume":"76","author":"S Benzekry","year":"2016","unstructured":"Benzekry, S., Tracz, A., Mastri, M., Corbelli, R., Barbolosi, D. & Ebos, J. M. Modeling Spontaneous Metastasis following Surgery: An In Vivo-In Silico Approach. Cancer Res. 76, 535\u2013547 (2016).","journal-title":"Cancer Res"},{"key":"BFsrep36173_CR27","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1258\/002367788780746467","volume":"22","author":"P Workman","year":"1988","unstructured":"Workman, P. et al. UKCCCR guidelines for the welfare of animals in experimental neoplasia. Lab Anim 22, 195\u2013201(1988).","journal-title":"Lab Anim"},{"key":"BFsrep36173_CR28","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1007\/s00540-005-0323-3","volume":"19","author":"O Saito","year":"2005","unstructured":"Saito, O., Aoe, T. & Yamamoto, T. Analgesic effects of nonsteroidal antiinflammatory drugs, acetaminophen, and morphine in a mouse model of bone cancer pain. J Anesth 19, 218\u2013224 (2005).","journal-title":"J Anesth"},{"key":"BFsrep36173_CR29","doi-asserted-by":"crossref","unstructured":"Lavielle, M. Mixed effects models for the population approach. Boca Raton, Florida, Chapman and Hall\/CRC (2014).","DOI":"10.1201\/b17203"},{"key":"BFsrep36173_CR30","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.csda.2004.07.002","volume":"49","author":"E Kuhn","year":"2005","unstructured":"Kuhn, E. & Lavielle, M. Maximum likelihood estimation in nonlinear mixed effects models. Comp Stat Data An 49, 1020\u20131038 (2005).","journal-title":"Comp Stat Data An"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep36173.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36173","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36173.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T07:17:08Z","timestamp":1672903028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep36173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,4]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep36173"],"URL":"https:\/\/doi.org\/10.1038\/srep36173","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,4]]},"assertion":[{"value":"10 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.C. is has worked as consultant for Celgene, Sanofi, Pfizer, Pierre Fabre and Roche. R.F. has worked as consultant for Roche. The other authors have no Competiting Interest to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36173"}}