Evidence map›Paper›PMID 26738797›Full record

ArticleScience translational medicine2016

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Melodi Javid Whitley, Diana M Cardona, Alexander L Lazarides, Ivan Spasojevic, Jorge M Ferrer, Joan Cahill, Chang-Lung Lee, Matija Snuderl, Dan G Blazer, E Shelley Hwang and 16 more

Open access · greenAbstract readClinical Trial, Phase I
In one paragraph

Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 3 pooled it
33.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 3 syntheses or guidelines pooled it, 286 citations in OpenAlex.

  1. Pooled it
  2. Molecular fluorophores for in vivo bioimaging in the second near-infrared window.European journal of nuclear medicine and molecular imaging · 2022
    Pooled it
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  12. Radiation Oncology-Biology Integration Network: Bridging the Gap between Biological Research and Clinical Practice.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
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  15. Translation of Intraoperative Molecular Imaging for Clinical Use.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026
    Review
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77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 1 country.

Melodi Javid WhitleyDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Medical Science Training Program, Duke University Medical Center, Durham, NC 27710, USA.
Diana M CardonaDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Alexander L LazaridesSchool of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Ivan SpasojevicDepartment of Medicine, Duke University Medical Center, Durham, NC 27710, USA. PK/PD Core Laboratory, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
Jorge M FerrerLumicell Inc., Wellesley, MA 02481, USA.
Joan CahillDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Chang-Lung LeeDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Matija SnuderlEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Dan G BlazerDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
E Shelley HwangDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Rachel A GreenupDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Paul J MoscaDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Jeffrey K MitoDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Medical Science Training Program, Duke University Medical Center, Durham, NC 27710, USA.
Kyle C CuneoDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Nicole A LarrierDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Erin K O'ReillyDuke Translational Medicine Institute, Regulatory Affairs Group, Duke University Medical Center, NC 27710, USA.
Richard F RiedelDepartment of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
William C EwardDepartment of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
David B StrasfeldLumicell Inc., Wellesley, MA 02481, USA.
Dai FukumuraEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Rakesh K JainEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
W David LeeLumicell Inc., Wellesley, MA 02481, USA.
Linda G GriffithDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Moungi G BawendiDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
David G KirschDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. david.kirsch@duke.edu.
Brian E BrigmanDepartment of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Duke Medical Center · USDuke University Hospital · USHarvard University · USMassachusetts Institute of Technology · USMassachusetts General Hospital · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Duke CTSA (Composite)UL1TR001117 · NCATS · DUKE UNIVERSITY · PI BOULWARE, LEIGH E, LI, JENNIFER S · 2013 to 2017
$41.3M
Vascular Normalization: Rolse of Perivascular CellsP01CA080124 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2000 to 2016
$35.0M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
Probing Tumor Microenvironment Using NanotechnologyR01CA126642 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2008 to 2012
$8.3M
Dissecting Pediatric Brain Tumor Microenvironment to Improve TreatmentR35CA197743 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2015 to 2020
$5.7M
NO in Tumor Angiogenesis,Microcirculation &Rad.TherapyR01CA096915 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI · 2002 to 2012
$3.0M
Engineered imaging nanoparticle for realtime detection of cancer in the tumor bedU43CA165024 · NCI · LUMICELL, INC. · PI LEE, W. DAVID · 2011 to 2011
$213k
NCATS NIH HHS UL1 TR001117NCATS NIH HHS UL1TR001117NCI NIH HHS 1U43CA165024NCI NIH HHS 5P30-CA-014236-38NCI NIH HHS P01 CA080124NCI NIH HHS P30 CA014051NCI NIH HHS P30 CA014236NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA096915NCI NIH HHS R01 CA126642NCI NIH HHS R35 CA197743NCI NIH HHS U43 CA165024NIGMS NIH HHS T32 GM007171NIGMS NIH HHS T32GM007171
6 · The paper itself

Abstract

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.

Indexed as

AnimalsBreast NeoplasmsDiagnostic ImagingDisease Models, AnimalFemaleFluorescent DyesHumansInjections, IntravenousMetabolomeMiceNeoplasmsPeptide HydrolasesSarcomaTissue DistributionFluorescent DyesPeptide Hydrolases

Identifiers

PMID26738797
PMCPMC4794335
OpenAlexW2240104466

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.