Evidence map›Paper›PMID 34642899›Full record

ArticleMolecular imaging and biology2023

Side-by-Side Comparison of uPAR-Targeting Optical Imaging Antibodies and Antibody Fragments for Fluorescence-Guided Surgery of Solid Tumors.

Victor M Baart, Labrinus van Manen, Shadhvi S Bhairosingh, Floris A Vuijk, Luisa Iamele, Hugo de Jonge, Claudia Scotti, Massimo Resnati, Robert A Cordfunke, Peter J K Kuppen and 4 more

Open access · hybridAbstract readComparative Study
In one paragraph

Article in Molecular imaging and biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

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  11. Synthesis of site-specific Fab-drug conjugates using ADP-ribosyl cyclases.Protein science : a publication of the Protein Society · 2024
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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

14 authors at 4 institutions in 2 countries.

Victor M BaartDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands. V.M.Baart@lumc.nl.
Labrinus van ManenDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Shadhvi S BhairosinghDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Floris A VuijkDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Luisa IameleUnit of Immunology and General Pathology, Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Hugo de JongeUnit of Immunology and General Pathology, Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Claudia ScottiUnit of Immunology and General Pathology, Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Massimo ResnatiAge Related Diseases Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
Robert A CordfunkeDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Peter J K KuppenDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Andrew P MazarMonopar Therapeutics, Wilmette, IL, USA.
Jacobus BurggraafDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Alexander L VahrmeijerDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Cornelis F M SierDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Medical Center · NLUniversity of Pavia · ITCentre for Human Drug Research · NLPercuros (Netherlands) · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeRadical resection is paramount for curative oncological surgery. Fluorescence-guided surgery (FGS) aids in intraoperative identification of tumor-positive resection margins. This study aims to assess the feasibility of urokinase plasminogen activator receptor (uPAR) targeting antibody fragments for FGS in a direct comparison with their parent IgG in various relevant in vivo models. PROCEDURES: Humanized anti-uPAR monoclonal antibody MNPR-101 (uIgG) was proteolytically digested into F(ab')2 and Fab fragments named uFab2 and uFab. Surface plasmon resonance (SPR) and cell assays were used to determine in vitro binding before and after fluorescent labeling with IRDye800CW. Mice bearing subcutaneous HT-29 human colonic cancer cells were imaged serially for up to 120 h after fluorescent tracer administration. Imaging characteristics and ex vivo organ biodistribution were further compared in orthotopic pancreatic ductal adenocarcinoma (BxPc-3-luc2), head-and-neck squamous cell carcinoma (OSC-19-luc2-GFP), and peritoneal carcinomatosis (HT29-luc2) models using the clinical Artemis fluorescence imaging system.

resultsUnconjugated and conjugated uIgG, uFab2, and uFab specifically recognized uPAR in the nanomolar range as determined by SPR and cell assays. Subcutaneous tumors were clearly identifiable with tumor-to-background ratios (TBRs) > 2 after 72 h for uIgG-800F and 24 h for uFab2-800F and uFab-800F. For the latter two, mean fluorescence intensities (MFIs) dipped below predetermined threshold after 72 h and 36 h, respectively. Tumors were easily identified in the orthotopic models with uIgG-800F consistently having the highest MFIs and uFab2-800F and uFab-800F having similar values. In biodistribution studies, kidney and liver fluorescence approached tumor fluorescence after uIgG-800F administration and surpassed tumor fluorescence after uFab2-800F or uFab-800F administration, resulting in interference in the abdominal orthotopic mouse models.

conclusionsIn a side-by-side comparison, FGS with uPAR-targeting antibody fragments compared with the parent IgG resulted in earlier tumor visualization at the expense of peak fluorescence intensity.

Indexed as

Pancreatic NeoplasmsReceptors, Urokinase Plasminogen ActivatorAnimalsAntibodies, Monoclonal, HumanizedCell Line, TumorFluorescent DyesHumansImmunoglobulin Fab FragmentsImmunoglobulin GMiceOptical ImagingTissue DistributionAntibodies, Monoclonal, HumanizedFluorescent DyesImmunoglobulin Fab FragmentsImmunoglobulin GReceptors, Urokinase Plasminogen ActivatorColon cancerFabF(ab’)2FluorescenceFluorescence-guided surgeryHead and neck cancerIgGImage-guided surgeryNear infraredOral cancerPancreatic canceruPARUrokinase plasminogen activator receptor

Identifiers

PMID34642899
PMCPMC9970952
OpenAlexW3206525948

What OpenQuestion holds

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LicenceCC BY
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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.