Contrast Agent Mass Spectrometry Imaging Reveals Tumor Heterogeneity
Abstract
Mapping intratumoral heterogeneity such as vasculature and margins is important during intraoperative applications. Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated potential for intraoperative tumor imaging using validated MS profiles. The clinical translation of DESI-MS into a universal label-free imaging technique thus requires access to MS profiles characteristic to tumors and healthy tissues. Here, we developed contrast agent mass spectrometry imaging (CA-MSI) that utilizes a magnetic resonance imaging (MRI) contrast agent targeted to disease sites, as a label, to reveal tumor heterogeneity in the absence of known MS profiles. Human breast cancer tumors grown in mice were subjected to CA-MSI using Gadoteridol revealing tumor margins and vasculature from the localization of [Gadoteridol+K](+) and [Gadoteridol+Na](+) adducts, respectively. The localization of the [Gadoteridol+K](+) adduct as revealed through DESI-MS complements the in vivo MRI results. DESI-MS imaging is therefore possible for tumors for which no characteristic MS profiles are established. Further DESI-MS imaging of the flux of the contrast agent through mouse kidneys was performed indicating secretion of the intact label.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Breast cancer tumors developed in mice were investigated by CA-MSI using Gadoteridol, revealing tumor margins and vasculature by localizing contrast agents.
“Breast cancer tumors developed in mice were investigated by CA-MSI using Gadoteridol, revealing tumor margins and vasculature by localizing the contrast agents.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [145]
Integration of 2D MSI with 3D MRI was able to monitor MRI contrast agents.
“Integration of 2D MSI with 3D MRI was able to monitor MRI contrast agents [145].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [145]
Combination of MSI with other techniques is prospective for bridging gaps between unalike scales.
“Thus, a combination of MSI with other techniques is prospective for bridging the gaps between unalike scales [145,146].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [145]
Cites
Breast cancer statistics, 2013
Desantis, C. E., Ma, J., Bryan, L. N., & Jemal, A. (2013) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21203 · Cited by 2,142 · see citing works
Cooks, R. G., Ouyang, Z., Takáts, Z., & Wiseman, J. M. (2006) · Science · doi:10.1126/science.1119426 · Cited by 1,483 · see citing works
McDonnell, L. A., & Heeren, R. M. A. (2007) · Mass Spectrometry Reviews · doi:10.1002/mas.20124 · Cited by 1,082 · see citing works
Wiseman, J. M., Ifa, D. R., Song, Q., & Cooks, R. G. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200602449 · Cited by 627 · see citing works
Self-citationIntraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry
Balog, J., Sasi-Szabó, L., Kinross, J. K., Lewis, M. R., Muirhead, L. J., Veselkov, K., Mirnezami, R., Dezsö, B., Damjanovich, L., Darzi, A. W., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005623 · Cited by 611 · see citing works
Mass spectrometry imaging under ambient conditions
Wu, C., Dill, A. L., Eberlin, L. S., Cooks, R. G., & Ifa, D. R. (2012) · Mass Spectrometry Reviews · doi:10.1002/mas.21360 · Cited by 487 · see citing works
Self-citationClassifying Human Brain Tumors by Lipid Imaging with Mass Spectrometry
Eberlin, L. S., Norton, I. H., Dill, A. L., Golby, A. J., Ligon, K. L., Santagata, S., Cooks, R. G., & Agar, N. Y. R. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-2465 · Cited by 294 · see citing works
Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors
Eberlin, L. S., Norton, I. H., Orringer, D. A., Dunn, I. F., Liu, X., Ide, J. L., Jarmusch, A. K., Ligon, K. L., Jolesz, F. A., Golby, A. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215687110 · Cited by 289 · see citing works
Eberlin, L. S., Ferreira, C. R., Dill, A. L., Ifa, D. R., & Cooks, R. G. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.05.006 · Cited by 258 · see citing works
Self-citationCalligaris, D., Caragacianu, D. L., Liu, X., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408129111 · Cited by 247 · see citing works
Becker, J. S., Matusch, A., & Wu, B. (2014) · Analytica Chimica Acta · doi:10.1016/j.aca.2014.04.048 · Cited by 239 · see citing works
Esbona, K., Li, Z., & Wilke, L. G. (2012) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2492-2 · Cited by 232 · see citing works
Identification of Biological Tissues by Rapid Evaporative Ionization Mass Spectrometry
Balog, J., Szaniszló, T., Schaefer, K.-C., et al. (2010) · Analytical Chemistry · doi:10.1021/ac101283x · Cited by 231 · see citing works
Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging
Eberlin, L. S., Tibshirani, R. J., Zhang, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400274111 · Cited by 227 · see citing works
Amini‐Nik, S., Kraemer, D., Cowan, M. L., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013053 · Cited by 215 · see citing works
Eberlin, L. S., Dill, A. L., Costa, A. B., et al. (2010) · Analytical Chemistry · doi:10.1021/ac9029482 · Cited by 192 · see citing works
Lipidomics: An analysis of cellular lipids by ESI-MS
Milne, S. B., Ivanova, P. T., Forrester, J. S., et al. (2006) · Methods · doi:10.1016/j.ymeth.2006.05.014 · Cited by 172 · see citing works
Ambient molecular imaging by desorption electrospray ionization mass spectrometry
Wiseman, J. M., Ifa, D. R., Venter, A. R., & Cooks, R. G. (2008) · Nature Protocols · doi:10.1038/nprot.2008.11 · Cited by 172 · see citing works
Self-citationDill, A. L., Eberlin, L. S., Zheng, C., Costa, A. B., Ifa, D. R., Liang Cheng, C., Masterson, T. A., Koch, M. O., Olga Vitek, A., & Cooks, R. G. (2010) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-010-4259-6 · Cited by 161 · see citing works
Self-citationGuenther, S., Muirhead, L. J., Speller, A. V. M., Golf, O., Strittmatter, N., Ramakrishnan, R., Goldin, R. D., Jones, E. A., Veselkov, K., Nicholson, J. K., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2258 · Cited by 159 · see citing works
Mass spectrometric imaging of lipids using desorption electrospray ionization
Dill, A. L., Ifa, D. R., Manicke, N. E., et al. (2009) · Journal of Chromatography B · doi:10.1016/j.jchromb.2008.12.058 · Cited by 158 · see citing works
Self-citationPhysicochemical Properties of Gadoteridol and Other Magnetic Resonance Contrast Agents
Tweedle, M. F. (1992) · Investigative Radiology · doi:10.1097/00004424-199208001-00002 · Cited by 158 · see citing works
Eberlin, L. S., Ferreira, C. R., Dill, A. L., Ifa, D. R., Liang Cheng, C., & Cooks, R. G. (2011) · ChemBioChem · doi:10.1002/cbic.201100411 · Cited by 151 · see citing works
Self-citationDill, A. L., Ifa, D. R., Manicke, N. E., et al. (2009) · Analytical Chemistry · doi:10.1021/ac901028b · Cited by 133 · see citing works
Self-citationDiagnosis of Nephrogenic Systemic Fibrosis by means of Elemental Bioimaging and Speciation Analysis
Birka, M., Wentker, K. S., Lusmöller, E., et al. (2015) · Analytical Chemistry · doi:10.1021/ac504488k · Cited by 129 · see citing works
Schäfer, K., Balog, J., Szaniszló, T., et al. (2011) · Analytical Chemistry · doi:10.1021/ac201251s · Cited by 108 · see citing works
Gerbig, S., Golf, O., Balog, J., Dénes, J., Baranyai, Z., Zaránd, A., Rásó, E., Tı́már, J., & Takáts, Z. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-5841-x · Cited by 102 · see citing works
Changes in breast cancer therapy because of pathology second opinions
Staradub, V. L., Messenger, K. A., Hao, N., Wiely, E. L., & Morrow, M. (2002) · Annals of Surgical Oncology · doi:10.1007/bf02574516 · Cited by 91 · see citing works
Ultrafast Extraction of Proteins from Tissues Using Desorption by Impulsive Vibrational Excitation
Kwiatkowski, M., Wurlitzer, M., Omidi, M., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201407669 · Cited by 55 · see citing works
Valdes, P. A., Moses, Z. B., Kim, A., Belden, C. J., Wilson, B. C., Paulsen, K. D., Roberts, D. W., & Harris, B. T. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31826775a1 · Cited by 48 · see citing works
Atmospheric-pressure Molecular Imaging of Biological Tissues and Biofilms by LAESI Mass Spectrometry
Nemes, P., & Vértes, Á. (2010) · Journal of Visualized Experiments · doi:10.3791/2097 · Cited by 29 · see citing works
Elemental imaging of MRI contrast agents: benchmarking of LA-ICP-MS to MRI
Pugh, J., Cox, A. G., McLeod, C. W., et al. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-5973-z · Cited by 27 · see citing works
Imaging Patients With Kidney Disease: How Do We Approach Contrast-Related Toxicity?
Perazella, M. A., & Reilly, R. F. (2010) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e3181f016e6 · Cited by 26 · see citing works
Sussulini, A., Wiener, E., Marnitz, T., et al. (2012) · Contrast Media & Molecular Imaging · doi:10.1002/cmmi.1509 · Cited by 26 · see citing works
Janfelt, C., Wellner, N., Hansen, H. S., et al. (2013) · Journal of Mass Spectrometry · doi:10.1002/jms.3166 · Cited by 21 · see citing works
Perspectives and Retrospectives in Mass Spectrometry: One View
Cooks, R. G., Ifa, D. R., Sharma, G., et al. (2010) · European Journal of Mass Spectrometry · doi:10.1255/ejms.1073 · Cited by 16 · see citing works
Self-citationElemental analysis in biotechnology
Hann, S., Dernovics, M., & Koellensperger, G. (2014) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.08.008 · Cited by 11 · see citing works
In vivo molecular imaging by LAESI MS
Piggee, C. A. (2008) · Analytical Chemistry · doi:10.1021/ac086126c · Cited by 5 · see citing works
Petersein, J., Saini, S., Mitchell, D. G., et al. (1995) · American Journal of Roentgenology · doi:10.2214/ajr.165.5.7572495 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Porta Siegel, T., Hamm, G., Bunch, J., Cappell, J., Fletcher, J. S., & Schwamborn, K. (2018) · Molecular Imaging and Biology · doi:10.1007/s11307-018-1267-y · Cited by 187 · see citing works
Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis
Subhan, M. A., Parveen, F., Filipczak, N., Yalamarty, S. S. K., & Torchilin, V. P. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13030389 · Cited by 98 · see citing works
“Integration of 2D MSI with 3D MRI was able to monitor MRI contrast agents [145].”
Backgroundde Maar, J. S., Sofias, A. M., Porta Siegel, T., Vreeken, R. J., Moonen, C., Bos, C., & Deckers, R. (2020) · Theranostics · doi:10.7150/thno.38625 · Cited by 71 · see citing works
- Authors
- Tata, A., Zheng, J., Ginsberg, H. J., Jaffray, D. A., Ifa, D. R., & Zarrine-Afsar, A.
- Affiliations
- University Health Network (CA)
- St. Michael's Hospital (CA)
- York University (CA)
- Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, Ontario M5G-1P5, Canada
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-07-15
- Volume
- 87
- Issue
- 15
- Pages
- 7683-7689
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W828489942
- Cited by
- 34
- References
- 39
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 4
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Keywords
- tumor heterogeneity, intratumoral heterogeneity, gadolinium-based MRI contrast agents, gadoteridol, desorption electrospray ionization mass spectrometry, label-free imaging, tumor vasculature, tumor margin, breast cancer xenografts
- MeSH terms
- Animals, Breast Neoplasms, Contrast Media, Female, Humans, Magnetic Resonance Imaging, Spectrometry, Mass, Electrospray Ionization, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
