The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer
Open accessAbstract
Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“and identification of residual cancer after surgery in humans through a protease-activated fluorescent probe.91”
From Early detection of pancreatic cancer (2020) · cites this paper as [91]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fisher, B., Anderson, S., Bryant, J., Margolese, R. G., Deutsch, M., Fisher, E. R., Jeong, J.-H., & Wolmark, N. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa022152 · Cited by 6,249
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121 · cited 1×
“Tumor-bearing mice Primary soft tissue sarcomas were generated using the previously described alleles, LSLKras(37), Braf(38), p53 (39), and LSL-YFP(40).”
MethodDistinct role of macrophages in different tumor microenvironments
Lewis, C. E., & Pollard, J. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4005 · Cited by 2,225 · cited 1×
“The labeling of tumor-associated macrophages likely occurs because these cells also express high levels of proteases (24), and the intraoperative identification and removal of these cells may, in fact, be beneficial to patients because these cells are associated with tumor progression and metastasis (25, 26).”
BackgroundPower and sample size calculations
Dupont, W. D., & Plummer, W. D. (1990) · Controlled Clinical Trials · doi:10.1016/0197-2456(90)90005-m · Cited by 2,112 · cited 1×
“Sample sizes were selected before initiating the study based on previous intraoperative imaging studies conducted in the laboratory (17), and power calculations were performed as described previously (30).”
MethodAnalysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,927
O’Sullivan, B., Davis, A. M., TURCOTTE, R. E., Bell, R. S., Catton, C., Chabot, P., Wunder, J. S., Kandel, R. A., Goddard, K., Sadura, A., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09292-9 · Cited by 1,602
Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy
Lin, E. Y., Nguyen, A. V., Russell, R. G., & Pollard, J. W. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.6.727 · Cited by 1,594 · cited 1×
“The labeling of tumor-associated macrophages likely occurs because these cells also express high levels of proteases (24), and the intraoperative identification and removal of these cells may, in fact, be beneficial to patients because these cells are associated with tumor progression and metastasis (25, 26).”
BackgroundIn vivo imaging of tumors with protease-activated near-infrared fluorescent probes
Weissleder, R., Tung, C., Mahmood, U., & Bogdanov, A. A., Jr. (1999) · Nature Biotechnology · doi:10.1038/7933 · Cited by 1,591 · cited 3×
“Protease-activated probes may provide increased tumor to normal contrast as they are designed to be optically inactive until cleaved by proteases that are highly expressed in tumors, like cathepsin proteases and matrix metalloproteases (MMPs) (13, 22-24).”
Backgroundvan Dam, G. M., Themelis, G., Crane, L. M. A., Harlaar, N. J., Pleijhuis, R. G., Kelder, W., Sarantopoulos, A., de Jong, J. S., Arts, H. J. G., van der Zee, A. G. J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2472 · Cited by 1,585
Yang, J., Chang, A. E., Baker, A., Sindelar, W. F., Danforth, D. N., Topalian, S. L., DeLaney, T. F., GLATSTEIN, E. J., Steinberg, S. M., Merino, M. J., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.1.197 · Cited by 1,541 · cited 3×
“Although radiation therapy significantly improves local recurrence-free survival for the entire population (1-4), the majority of patients, who would have achieved local control with surgery alone, derive no benefit from adjuvant radiation therapy.”
Background
Research works printed but not linked: 1
- D. L. Taylor Y.-l. Wang Fluorescence microscopy of living cells in culture in Methods in Cell Biology L. Wilson Ed. (Academic Press San Diego CA 1989) vol. 29 pp. 1–328.
Cited by
Sorted by citations
Challenges and strategies in anti-cancer nanomedicine development: An industry perspective
Hare, J. I., Lammers, T., Ashford, M. B., Puri, S., Storm, G., & Barry, S. T. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.025 · Cited by 1,279
Near‐Infrared‐II Molecular Dyes for Cancer Imaging and Surgery
Zhu, S., Tian, R., Antaris, A. L., Chen, X. S., & Dai, H. (2019) · Advanced Materials · doi:10.1002/adma.201900321 · Cited by 976
Recent progresses in small-molecule enzymatic fluorescent probes for cancer imaging
Liu, H.-W., Chen, L., Xu, C., Li, Z., Zhang, H., Zhang, X.-B., & Tan, W. (2018) · Chemical Society Reviews · doi:10.1039/c7cs00862g · Cited by 948
Light in diagnosis, therapy and surgery
Yun, S. H., & Kwok, S. J. J. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0008 · Cited by 835
Renal clearable catalytic gold nanoclusters for in vivo disease monitoring
Loynachan, C. N., Soleimany, A. P., Dudani, J. S., Lin, Y., Najer, A., Bekdemir, A., Chen, Q., Bhatia, S. N., & Stevens, M. M. (2019) · Nature Nanotechnology · doi:10.1038/s41565-019-0527-6 · Cited by 524
Beyond the margins: real-time detection of cancer using targeted fluorophores
Zhang, R. R., Schroeder, A. B., Grudzinski, J. J., Rosenthal, E. L., Warram, J. M., Pinchuk, A. N., Eliceiri, K. W., Kuo, J. S., & Weichert, J. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.212 · Cited by 503
Early detection of pancreatic cancer
Pereira, S. P., Oldfield, L., Ney, A., Hart, P. A., Keane, M. G., Pandol, S. J., Li, D., Greenhalf, W., Jeon, C. Y., Koay, E. J., et al. (2020) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30416-9 · Cited by 482
Latest developments in molecular tracers for fluorescence image-guided cancer surgery
Hernot, S., van Manen, L., Debie, P., Mieog, J. S. D., & Vahrmeijer, A. L. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30317-1 · Cited by 496
Advanced Photosensitizer Activation Strategies for Smarter Photodynamic Therapy Beacons
Luby, B. M., Walsh, C. D., & Zheng, G. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201805246 · Cited by 422
Molecular imaging and disease theranostics with renal-clearable optical agents
Cheng, P., & Pu, K. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00328-6 · Cited by 418
Nagaya, T., Nakamura, Y. A., Choyke, P. L., & Kobayashi, H. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00314 · Cited by 415
“LUM015 is optically inactive under normal conditions, but upon proteolytic cleavage, a covalently attached quencher molecule is released and fluorescence signal greatly intensifies (103).”
BackgroundInfluentialFundamentals and developments in fluorescence-guided cancer surgery
Mieog, J. S. D., Achterberg, F. B., Zlitni, A., Hutteman, M., Burggraaf, J., Swijnenburg, R., Gioux, S., & Vahrmeijer, A. L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00548-3 · Cited by 415
Lamberts, L. E., Koch, M., de Jong, J. S., Adams, A. L. L., Glatz, J., Kranendonk, M. E. G., van Scheltinga, A. G. T. T., Jansen, L., de Vries, J., Hooge, M. N. L., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0437 · Cited by 285
Real-time fluorescence imaging in intraoperative decision making for cancer surgery
Lauwerends, L. J., van Driel, P. B. A. A., de Jong, R. J. B., Hardillo, J. A., Koljenović, S., Puppels, G. J., Mezzanotte, L., Löwik, C. W. G. M., Rosenthal, E. L., Vahrmeijer, A. L., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30600-8 · Cited by 294
Fluorescence image-guided tumour surgery
Wang, K., Du, Y., Zhang, Z., He, K., Cheng, Z., Yin, L., Dong, D., Li, C., Li, W., Hu, Z., et al. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-022-00017-1 · Cited by 265
Activatable molecular probes for fluorescence-guided surgery, endoscopy and tissue biopsy
Zhang, Y., Zhang, G., Zeng, Z., & Pu, K. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00525a · Cited by 237
Chen, C., Tian, R., Zeng, Y., Chu, C., & Liu, G. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00734 · Cited by 218
Synthetic biomarkers: a twenty-first century path to early cancer detection
Kwong, G. A., Ghosh, S., Gamboa, L., Patriotis, C., Srivastava, S., & Bhatia, S. N. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00389-3 · Cited by 218
The Future of Cysteine Cathepsins in Disease Management
Kramer, L., Türk, V., & Turk, B. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.06.003 · Cited by 194
Voskuil, F. J., Steinkamp, P. J., Zhao, T., van der Vegt, B., Koller, M., Doff, J. J., Jayalakshmi, Y., Hartung, J., Gao, J., Sumer, B. D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16814-4 · Cited by 188
Recent Advances on Activatable NIR‐II Fluorescence Probes for Biomedical Imaging
Tang, Y., Pei, F., Lü, X., Fan, Q., & Huang, W. (2019) · Advanced Optical Materials · doi:10.1002/adom.201900917 · Cited by 166
Peptide-based nanoprobes for molecular imaging and disease diagnostics
Zhang, P., Cui, Y., Anderson, C. F., Zhang, C., Li, Y., Wang, R., & Cui, H. (2018) · Chemical Society Reviews · doi:10.1039/c7cs00793k · Cited by 160
Activity-Based Fluorescence Diagnostics for Cancer
Fujita, K., & Urano, Y. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00612 · Cited by 156
Oncologic Procedures Amenable to Fluorescence-guided Surgery
Tipirneni, K. E., Warram, J. M., Moore, L. S., Prince, A. C., de Boer, E., Jani, A. H., Wapnir, I., Liao, J. C., Bouvet, M., Behnke, N. K., et al. (2016) · Annals of Surgery · doi:10.1097/sla.0000000000002127 · Cited by 161
“Another study (NCT01626066) used a PEGylated, proteaseactivated fluorescent probe (LUM015, Lumicell, Inc, Wellesley, MA), to demonstrate tumor-specific labeling in both human breast cancer and soft tissue sarcomas.(55) In addition, they found LUM015 to be safely administered and tolerated for detection of tumor-specif…”
InfluentialCysteine Cathepsins in Tumor-Associated Immune Cells
Jakoš, T., Pišlar, A. H., Jewett, A., & Kos, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02037 · Cited by 145
“LUM-015, comprising of fluorescence quencher molecule attached through tetrapeptide GGRK to polyethylene glycol linker and Cy5 fluorophore, was the first pan-cathepsin imaging probe to be translated from bench to bedside (114).”
BackgroundLi, Q., Li, S., He, S., Chen, W., Cheng, P., Zhang, Y., Miao, Q., & Pu, K. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202000035 · Cited by 146
Review of methods for intraoperative margin detection for breast conserving surgery
Maloney, B. W., McClatchy, D. M., Pogue, B. W., Paulsen, K. D., Wells, W. A., & Barth, R. J. (2018) · Journal of Biomedical Optics · doi:10.1117/1.jbo.23.10.100901 · Cited by 153
Tackling standardization in fluorescence molecular imaging
Koch, M., Symvoulidis, P., & Ntziachristos, V. (2018) · Nature Photonics · doi:10.1038/s41566-018-0221-5 · Cited by 144
AND-gate contrast agents for enhanced fluorescence-guided surgery
Widen, J. C., Tholen, M., Yim, J. J., Antaris, A., Casey, K. M., Rogalla, S., Klaassen, A., Sorger, J., & Bogyo, M. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00616-6 · Cited by 142
Ultrasensitive tumour-penetrating nanosensors of protease activity
Kwon, E. J., Dudani, J. S., & Bhatia, S. N. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0054 · Cited by 131
“Optimizing substrate presentation is a possible solution to the challenge of engineering protease specificity for synthetic substrates 8,19 that has been relatively unexplored in the literature and could also be leveraged in other enzyme-activated technologies 20,21 .”
Fluorescent Probes for Imaging in Humans: Where Are We Now?
Seah, D., Cheng, Z., & Vendrell, M. (2023) · ACS Nano · doi:10.1021/acsnano.3c03564 · Cited by 132
Physiological principles underlying the kidney targeting of renal nanomedicines
Huang, Y., Ning, X., Ahrari, S., Cai, Q., Rajora, N., Saxena, R., Yu, M., & Zheng, J. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00819-z · Cited by 139
“LUM015 (ref.”
Multiplexed imaging in oncology
Andreou, C., Weissleder, R., & Kircher, M. F. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00891-5 · Cited by 132
Molecular imaging probes for multi-spectral optoacoustic tomography
Gujrati, V., Mishra, A., & Ntziachristos, V. (2017) · Chemical Communications · doi:10.1039/c6cc09421j · Cited by 120
Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins
Boonstra, M. C., de Geus, S. W. L., Prevoo, H. A. J. M., Hawinkels, L. J. A. C., de Velde, C. J. H. V., Kuppen, P. J. K., Vahrmeijer, A. L., & Sier, C. F. M. (2016) · Biomarkers in Cancer · doi:10.4137/bic.s38542 · Cited by 120
Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity
Mac, Q. D., Mathews, D., Kahla, J. A., Stoffers, C. M., Delmas, O. M., Holt, B. A., Adams, A. B., & Kwong, G. A. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0358-7 · Cited by 121
Fan, Z., Zhao, J., Chai, X., & Li, L. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202104408 · Cited by 116
Imaging approaches to optimize molecular therapies
Weissleder, R., Schwaiger, M. C., Gambhir, S. S., & Hricak, H. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf3936 · Cited by 112
The Tumor Proteolytic Landscape: A Challenging Frontier in Cancer Diagnosis and Therapy
Vizovišek, M., Ristanovic, D., Menghini, S., Christiansen, M. G., & Schuerle, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052514 · Cited by 118
“been tested in a mouse-human phase I co-clinical trial, offering the first promising human data for this technique [260].”
MethodActivatable fluorescence: From small molecule to nanoparticle
Luby, B. M., Charron, D. M., MacLaughlin, C. M., & Zheng, G. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.08.010 · Cited by 107
Harnessing Protease Activity to Improve Cancer Care
Dudani, J. S., Warren, A., & Bhatia, S. N. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050549 · Cited by 103
“Activity-based potentially toxic therapeutic modalities (e.g., potent immunotherapies). may similarly benefit from selective activation in the tumor microenvironment.”
Miampamba, M., Liu, J., Harootunian, A. T., Gale, A. J., Baird, S. M., Chen, S. L., Nguyen, Q. T., Tsien, R. Y., & González, J. E. (2017) · Theranostics · doi:10.7150/thno.20678 · Cited by 101
“Protease-activated imaging agents utilize disease biochemistry to generate localized contrast and are a promising class of probes for in vivo visualization of cancer (14, 15).”
BackgroundEmerging Fluorescent Molecular Tracers to Guide Intra-Operative Surgical Decision-Making
Debie, P., & Hernot, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00510 · Cited by 99
“Clinical studies in breast cancer and soft tissue sarcoma patients showed that tumor imaging could be performed between 2 and 30 h after intravenous injection of this tracer (Whitley et al., 2016; Smith et al., 2018).”
Fluorescence image-guided surgery: a perspective on contrast agent development
Barth, C. W., & Gibbs, S. L. (2020) · Molecular-Guided Surgery: Molecules, Devices, and Applications · doi:10.1117/12.2545292 · Cited by 108
Ashton, J. R., Castle, K. D., Qi, Y. P., Kirsch, D. G., West, J. L., & Badea, C. T. (2018) · Theranostics · doi:10.7150/thno.22621 · Cited by 105
“Similarly, CT imaging to assess EPR could also be useful for selecting patients for intraoperative molecular imaging with fluorescent imaging agents that accumulate in tumors at least in part through EPR effects [70].”
BackgroundTargeted Optical Imaging Agents in Cancer: Focus on Clinical Applications
Joshi, B. P., & Wang, T. D. (2018) · Contrast Media & Molecular Imaging · doi:10.1155/2018/2015237 · Cited by 98
“(d) Representative ex vivo fluorescence images of resected normal humanmuscle and sarcoma along with corresponding histology ((c) and (d) reprinted with the permission from [89]).”
BackgroundInfluentialNear-Infrared Fluorescent Probes for the Detection of Cancer-Associated Proteases
Scott, J. I., Deng, Q., & Vendrell, M. (2021) · ACS Chemical Biology · doi:10.1021/acschembio.1c00223 · Cited by 97
Kennedy, K. M., Zilkens, R., Allen, W. M., Foo, K. Y., Fang, Q., Chin, L., Sanderson, R. W., Anstie, J. D., Wijesinghe, P., Curatolo, A., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-1240 · Cited by 94
“A small number of proof-of-principle studies in humans have been reported (19, 20, 22), but the efficacy of these techniques for reducing re-excision rates in BCS has not been determined.”
BackgroundActivity-Based Diagnostics: An Emerging Paradigm for Disease Detection and Monitoring
Soleimany, A. P., & Bhatia, S. N. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.01.013 · Cited by 94
“Cathepsin-responsive fluorescent probes [23,24] are currently under commercial development for in vivo tumor detection.”
Liu, R., Xu, Y., Xu, K., & Dai, Z. (2021) · Aggregate · doi:10.1002/agt2.23 · Cited by 93
Imaging of anticancer drug action in single cells
Miller, M. A., & Weissleder, R. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.41 · Cited by 92
Peptide probes for proteases – innovations and applications for monitoring proteolytic activity
Rodriguez-Rios, M., Megía-Fernández, A., Norman, D. J., & Bradley, M. (2022) · Chemical Society Reviews · doi:10.1039/d1cs00798j · Cited by 90
Emerging Intraoperative Imaging Modalities to Improve Surgical Precision
Alam, I. S., Steinberg, I., Vermesh, O., van den Berg, N. S., Rosenthal, E. L., van Dam, G. M., Ntziachristos, V., Gambhir, S. S., Hernot, S., & Rogalla, S. (2018) · Molecular Imaging and Biology · doi:10.1007/s11307-018-1227-6 · Cited by 97
Unkart, J., Chen, S. L., Wapnir, I., González, J. E., Harootunian, A. T., & Wallace, A. M. (2017) · Annals of Surgical Oncology · doi:10.1245/s10434-017-5991-3 · Cited by 88
Smith, B. L., Gadd, M. A., Lanahan, C. R., Rai, U., Tang, R., Rice-Stitt, T. L., Merrill, A. L., Strasfeld, D. B., Ferrer, J. M., Brachtel, E. F., et al. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4845-4 · Cited by 92
“The Lumicell (LUM) Imaging System (Lumicell, Wellesley, MA) includes LUM015, a novel PEGylated proteaseactivated far-red fluorescent imaging agent [21]; the LUM optical head, a hand-held probe, and sterile cover used to excite LUM015 and collect real-time fluorescent recordings; and software for image analysis.”
InfluentialFang, B., Shen, Y., Peng, B., Bai, H., Wang, L., Zhang, J., Hu, W., Fu, L., Zhang, W., Li, L., et al. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202207188 · Cited by 86
Xiang, Z., Zhao, J., Yi, D., Di, Z., & Li, L. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202106639 · Cited by 81
Small-Molecule Lanthanide Complexes Probe for Second Near-Infrared Window Bioimaging
Yang, Y., Wang, P., Lu, L., Fan, Y., Sun, C., Fan, L., Xu, C., El‐Toni, A. M., Alhoshan, M. S., & Zhang, F. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b00603 · Cited by 81
Cyanine Conjugate‐Based Biomedical Imaging Probes
Li, Y., Zhou, Y., Yue, X., & Dai, Z. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202001327 · Cited by 79
Wang, K., Wang, W., Zhang, X., Jiang, A.-Q., Yang, Y., & Zhu, H. (2021) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2021.116189 · Cited by 76
Galema, H. A., Meijer, R. P., Lauwerends, L. J., Verhoef, C. K., Burggraaf, J., Vahrmeijer, A. L., Hutteman, M., Keereweer, S., & Hilling, D. E. (2021) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2021.10.005 · Cited by 76
Huang, J., Chen, M., Whitley, M. J., Kuo, H.-C., Xu, E. S., Walens, A., Mowery, Y. M., Mater, D. V., Eward, W. C., Cardona, D. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15999 · Cited by 75
Miller, M. A., & Weissleder, R. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.05.023 · Cited by 74
Peptides for optical medical imaging and steps towards therapy
Staderini, M., Megía-Fernández, A., Dhaliwal, K., & Bradley, M. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.09.039 · Cited by 73
Yıldız, T., Gu, R., Zauscher, S., & Betancourt, T. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s174068 · Cited by 72
“…of tissue perfusion, fluorescence-guided surgery, 21,22 sentinel lymph-node mapping and general lymphography, 20,25–27 detection of prema-lignant/malignant lesions (ClinicalTrials.gov; NCT02113202 and NCT01972373), and tumor identification and margin detection, 24,28–30 among other applications.”
Bortot, B., Mangogna, A., Lorenzo, G. D., Stabile, G., Ricci, G., & Biffi, S. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-01926-y · Cited by 86
“LUM015 is a PEGylated protease-activated fluorescent imaging probe [94].”
BackgroundImage‐guided tumor surgery: The emerging role of nanotechnology
Wojtynek, N. E., & Mohs, A. M. (2020) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1624 · Cited by 76
Blau, R., Epshtein, Y., Pisarevsky, E., Tiram, G., Dangoor, S. I., Yeini, E., Krivitsky, A., Eldar‐Boock, A., Ben‐Shushan, D., Gibori, H., et al. (2018) · Theranostics · doi:10.7150/thno.23853 · Cited by 71
“Examples include the FDA-approved Lymphoseek®, a technetium 99mTc-dextran conjugate for sentinel lymph nodes (SLN) identification that has shown persistent SLN accumulation for at least 24 h [40], a polyethyleneglycol-bound (PEGylated) protease activatable fluorescent probe that is in a phase 1 clinical trial [41] and…”
Molecular imaging: design mechanism and bioapplications
Chen, L., Lyu, Y., Zhang, X., Zheng, L., Li, Q., Ding, D., Chen, F., Li, W., Li, W., Zhang, Y., et al. (2023) · Science China Chemistry · doi:10.1007/s11426-022-1461-3 · Cited by 69
Protease-Sensitive Nanomaterials for Cancer Therapeutics and Imaging
Anderson, C. F., & Cui, H. (2017) · Industrial & Engineering Chemistry Research · doi:10.1021/acs.iecr.7b00990 · Cited by 67
Protease Specificity: Towards In Vivo Imaging Applications and Biomarker Discovery
Vizovišek, M., Vidmar, R., Drąg, M., Fonovič, M., Salvesen, G. S., & Turk, B. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.07.003 · Cited by 67
Tibbitt, M. W., & Langer, R. (2017) · Accounts of Chemical Research · doi:10.1021/acs.accounts.6b00499 · Cited by 65
Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery
Smith, B. L., Hunt, K. K., Carr, D., Blumencranz, P. W., Hwang, E., Gadd, M. A., Stone, K., Dyess, D. L., Dodge, D. G., Valente, S. A., et al. (2023) · NEJM Evidence · doi:10.1056/evidoa2200333 · Cited by 62
Deployment and exploitation of nanotechnology nanomaterials and nanomedicine
Matteucci, F., Giannantonio, R., Calabi, F., Agostiano, A., Gigli, G., & Rossi, M. (2018) · AIP conference proceedings · doi:10.1063/1.5047755 · Cited by 61
Fujita, K., Kamiya, M., Yoshioka, T., Ogasawara, A., Hino, R., Kojima, R., Ueo, H., & Urano, Y. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c01189 · Cited by 60
Li, Q., Li, S., He, S., Chen, W., Cheng, P., Zhang, Y., Miao, Q., & Pu, K. (2020) · Angewandte Chemie · doi:10.1002/ange.202000035 · Cited by 56
Advances in fluorescent-image guided surgery
Landau, M. J., Gould, D. J., & Patel, K. M. (2016) · Annals of Translational Medicine · doi:10.21037/atm.2016.10.70 · Cited by 57
“LUM015 was injected intravenously into 15 patients with either invasive ductal carcinoma or soft tissue sarcoma and was well tolerated with no adverse pharmacological activity (36).”
BackgroundMethodInfluentialOptical Surgical Navigation for Precision in Tumor Resections
Harmsen, S., Teraphongphom, N. T., Tweedle, M. F., Basilion, J. P., & Rosenthal, E. L. (2017) · Molecular Imaging and Biology · doi:10.1007/s11307-017-1054-1 · Cited by 58
Duncan, R. (2017) · Journal of drug targeting · doi:10.1080/1061186x.2017.1358729 · Cited by 57
“Important new clinical imaging tools are also arriving including a cathespinactivated PEG-peptide conjugate (LUM015) for intraoperative imaging of residual disease [47] that is currently undergoing clinical evaluation in breast cancer [48].”
BackgroundRadiation Therapy for Soft Tissue Sarcoma
Larrier, N., Czito, B. G., & Kirsch, D. G. (2016) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2016.05.012 · Cited by 55
Optimization of a Protease Activated Probe for Optical Surgical Navigation
Yim, J. J., Tholen, M., Klaassen, A., Sorger, J., & Bogyo, M. S. (2017) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b00822 · Cited by 55
Advanced Photosensitizer Activation Strategies for Smarter Photodynamic Therapy Beacons
Luby, B. M., Walsh, C. D., & Zheng, G. (2018) · Angewandte Chemie · doi:10.1002/ange.201805246 · Cited by 54
Steinkamp, P. J., Pranger, B. K., Li, M., Linssen, M. D., Voskuil, F. J., Been, L. B., van Leeuwen, B. L., Suurmeijer, A. J. H., Nagengast, W. B., Kruijff, S., et al. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.245696 · Cited by 54
Advances and challenges in precision imaging
Hricak, H., Mayerhoefer, M. E., Herrmann, K., Lewis, J. S., Pomper, M. G., Hess, C. P., Riklund, K., Scott, A. M., & Weissleder, R. (2025) · The Lancet Oncology · doi:10.1016/s1470-2045(24)00395-4 · Cited by 56
Chowdhury, M. M., Singh, K., Albaghdadi, M. S., Khraishah, H., Mauskapf, A., Kessinger, C. W., Osborn, E. A., Kellnberger, S., Piao, Z., Cardenas, C. L. L., et al. (2020) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2020.04.007 · Cited by 52
Molecular probes for fluorescence image-guided cancer surgery
Ito, R., Kamiya, M., & Urano, Y. (2022) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2021.102112 · Cited by 56
Stein-Merlob, A. F., Hara, T., McCarthy, J. R., Mauskapf, A., Hamilton, J. A., Ntziachristos, V., Libby, P., & Jaffer, F. A. (2017) · Circulation Cardiovascular Imaging · doi:10.1161/circimaging.116.005813 · Cited by 51
Hwang, E., Beitsch, P. D., Blumencranz, P. W., Carr, D., Chagpar, A. B., Clark, L. P., Dekhne, N. S., Dodge, D. G., Dyess, D. L., Gold, L. P., et al. (2022) · JAMA Surgery · doi:10.1001/jamasurg.2022.1075 · Cited by 50
“On a permargin basis, the overall false-negative rate of the pFGS technology, defined as the proportion of false-negative images (19) of total images (1522), was 1.”
BackgroundMagnetically Actuated Protease Sensors for in Vivo Tumor Profiling
Schuerle, S., Dudani, J. S., Christiansen, M. G., Anikeeva, P., & Bhatia, S. N. (2016) · Nano Letters · doi:10.1021/acs.nanolett.6b02670 · Cited by 50
Advances in Diagnostic and Intraoperative Molecular Imaging of Pancreatic Cancer
Tummers, W. S., Willmann, J. K., Bonsing, B. A., Vahrmeijer, A. L., Gambhir, S. S., & Swijnenburg, R.-J. (2018) · Pancreas · doi:10.1097/mpa.0000000000001075 · Cited by 50
Intravascular Molecular Imaging: Near-Infrared Fluorescence as a New Frontier
Khraishah, H., & Jaffer, F. A. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.587100 · Cited by 49
Palmer, D. D., Dumont, J. R., Dexter, T. D., Prado, M. A. M., Finger, E. C., Bussey, T. J., & Saksida, L. M. (2021) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2021.107443 · Cited by 54
Kennedy, G. T., Holt, D. E., Azari, F. S., Bernstein, E. R., Nadeem, B., Chang, A. E., Sullivan, N. T., Segil, A., Desphande, C., Bensen, E. S., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1215 · Cited by 48
Cysteine cathepsins: A long and winding road towards clinics
Biasizzo, M., Javoršek, U., Vidak, E., Zarić, M., & Turk, B. (2022) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2022.101150 · Cited by 50
Intraoperative Fluorescence‐Guided Surgery in Head and Neck Squamous Cell Carcinoma
Lee, Y., Krishnan, G., Nishio, N., van den Berg, N. S., Lu, G., Martin, B. A., van Keulen, S., Colevas, A. D., Kapoor, S., Liu, J. T. C., et al. (2020) · The Laryngoscope · doi:10.1002/lary.28822 · Cited by 47
Fluorescence-Guided Surgery in the Surgical Treatment of Gliomas: Past, Present and Future
Sun, R., Cuthbert, H. J., & Watts, C. (2021) · Cancers · doi:10.3390/cancers13143508 · Cited by 50
Vasiljeva, O. S., Hostetter, D. R., Moore, S. J., & Winter, M. B. (2019) · Biological Chemistry · doi:10.1515/hsz-2018-0451 · Cited by 46
Smith, B. L., Lanahan, C. R., Specht, M. C., Kelly, B. N., Brown, C. L., Strasfeld, D. B., Ferrer, J. M., Rai, U., Tang, R., Rice-Stitt, T. L., et al. (2020) · Annals of Surgical Oncology · doi:10.1245/s10434-019-08158-1 · Cited by 51
Zhou, S., Jiang, L., Li, C., Mao, H. Z., Jiang, C., Wang, Z., Zheng, X., & Jiang, X. (2023) · Advanced Materials · doi:10.1002/adma.202212231 · Cited by 45
Suurs, F. V., Qiu, S., Yim, J. J., Schröder, C. P., Timmer‐Bosscha, H., Bensen, E. S., Santini, J. T., de Vries, E. G. E., Bogyo, M. S., & van Dam, G. M. (2020) · EJNMMI Research · doi:10.1186/s13550-020-00688-0 · Cited by 47
Metadata
- Authors
- Whitley, M. J., Cardona, D. M., Lazarides, A. L., Spasojevic, I., Ferrer, J. M., Cahill, J., Lee, C.-L., Snuderl, M., Blazer, D. G., Hwang, E. S., Greenup, R. A., Mosca, P. J., Mito, J. K., Cuneo, K. C., Larrier, N. A., O’Reilly, E. K., Riedel, R. F., Eward, W. C., Strasfeld, D. B., Fukumura, D., Jain, R. K., Lee, W. D., Griffith, L. G., Bawendi, M. G., Kirsch, D. G., & Brigman, B. E.
- Affiliations
- Duke Medical Center (US)
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
- Lumicell (United States) (US)
- Harvard University (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Kirsch, David G.
- Brigman, Brian E.
- ORCID
- Whitley, Melodi Javid
- Cardona, Diana M.
- Lazarides, Alexander L.
- Lee, Chang-Lung
- Snuderl, Matija
- Blazer, Dan G.
- Hwang, E. Shelley
- Greenup, Rachel A.
- Mosca, Paul J.
- Mito, Jeffrey K.
- Cuneo, Kyle C.
- O’Reilly, Erin K.
- Riedel, Richard F.
- Eward, William C.
- Fukumura, Dai
- Griffith, Linda G.
- Bawendi, Moungi G.
- Kirsch, David G.
- Brigman, Brian E.
- Venue
- Science Translational Medicine
- Published
- 2016-01-06
- Volume
- 8
- Issue
- 320
- Pages
- 320ra4-320ra4
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC4794335
- OpenAlex
- W2240104466
- Cited by
- 296
- References
- 40
- Citations by year
- 2026: 24 · 2025: 18 · 2024: 20 · 2023: 23 · 2022: 32 · 2021: 43 · 2020: 36 · 2019: 18 · 2018: 33 · 2017: 31 · 2016: 17
- FWCI
- 13.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- American Society of Clinical Oncology Advanced Clinical Research Award
- NIH (#T32GM007171)
- National Cancer Institute Small Business Innovation Research (#1U43CA165024)
- National Center for Advancing Translational Science (#UL1TR001117)
- Duke Comprehensive Cancer Center Support (5P30-CA-014236-38)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- tumor imaging, soft tissue sarcoma, breast cancer, local recurrence, intraoperative tumor detection, tumor bed, pharmacokinetics, lysine labeling
- MeSH terms
- Animals, Breast Neoplasms, Diagnostic Imaging, Disease Models, Animal, Female, Fluorescent Dyes, Humans, Injections, Intravenous, Neoplasms, Peptide Hydrolases, Sarcoma, Tissue Distribution, Mice, Metabolome
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
