Evidence map›Paper›PMID 25895046›Full record

ArticleInternational journal of cancer2015

Preclinical evaluation of a novel CEA-targeting near-infrared fluorescent tracer delineating colorectal and pancreatic tumors.

Martin C Boonstra, Berend Tolner, Boudewijn E Schaafsma, Leonora S F Boogerd, Hendrica A J M Prevoo, Guarav Bhavsar, Peter J K Kuppen, Cornelis F M Sier, Bert A Bonsing, John V Frangioni and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

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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

13 authors at 4 institutions in 3 countries.

Martin C BoonstraDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Berend TolnerDepartment of Oncology, Royal Free & University College Medical School, London, United Kingdom.
Boudewijn E SchaafsmaDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Leonora S F BoogerdDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Hendrica A J M PrevooDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Guarav BhavsarDepartment of Oncology, Royal Free & University College Medical School, London, United Kingdom.
Peter J K KuppenDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Cornelis F M SierDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Bert A BonsingDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
John V FrangioniDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
Cornelis J H van de VeldeDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Kerry A ChesterDepartment of Oncology, Royal Free & University College Medical School, London, United Kingdom.
Alexander L VahrmeijerDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Medical Center · NLThe Royal Free Hospital · GBBeth Israel Deaconess Medical Center · USUniversity College London · GB

Funding

Intraoperative Near-Infrared Fluorescence ImagingR01CA115296 · NCI · CURADEL, LLC · PI FRANGIONI, JOHN V · 2005 to 2014
$13.9M
NCI NIH HHS R01 CA115296
6 · The paper itself

Abstract

Surgery is the cornerstone of oncologic therapy with curative intent. However, identification of tumor cells in the resection margins is difficult, resulting in nonradical resections, increased cancer recurrence and subsequent decreased patient survival. Novel imaging techniques that aid in demarcating tumor margins during surgery are needed. Overexpression of carcinoembryonic antigen (CEA) is found in the majority of gastrointestinal carcinomas, including colorectal and pancreas. We developed ssSM3E/800CW, a novel CEA-targeted near-infrared fluorescent (NIRF) tracer, based on a disulfide-stabilized single-chain antibody fragment (ssScFv), to visualize colorectal and pancreatic tumors in a clinically translatable setting. The applicability of the tracer was tested for cell and tissue binding characteristics and dosing using immunohistochemistry, flow cytometry, cell-based plate assays and orthotopic colorectal (HT-29, well differentiated) and pancreatic (BXPC-3, poorly differentiated) xenogeneic human-mouse models. NIRF signals were visualized using the clinically compatible FLARE™ imaging system. Calculated clinically relevant doses of ssSM3E/800CW selectively accumulated in colorectal and pancreatic tumors/cells, with highest tumor-to-background ratios of 5.1 ± 0.6 at 72 hr postinjection, which proved suitable for intraoperative detection and delineation of tumor boarders and small (residual) tumor nodules in mice, between 8 and 96 hr postinjection. Ex vivo fluorescence imaging and pathologic examination confirmed tumor specificity and the distribution of the tracer. Our results indicate that ssSM3E/800CW shows promise as a diagnostic tool to recognize colorectal and pancreatic cancers for fluorescent-guided surgery applications. If successfully translated clinically, this tracer could help improve the completeness of surgery and thus survival.

Indexed as

Single-Chain AntibodiesAnimalsBenzenesulfonatesCaco-2 CellsCarcinoembryonic AntigenCell Line, TumorColorectal NeoplasmsDrug Evaluation, PreclinicalFemaleHCT116 CellsHT29 CellsHumansIndolesMiceMice, NudeNeoplasm TransplantationBenzenesulfonatesCarcinoembryonic AntigenIndolesIRDye 800CWSingle-Chain AntibodiesCEACAM5clinical translationimage guidedNIR fluorescencesurgery

Identifiers

PMID25895046
PMCPMC5080533
OpenAlexW2030541057

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.