Evidence map›Paper›PMID 41454065›Full record

ArticleEuropean journal of nuclear medicine and molecular imaging2026

Comparative theranostic efficacy of

Émilien N'Guessan, Florian Raes, Mitra Ahmadi, Sandrine Bacot, Laurent Dumas, Julien Leenhardt, Amaury du Moulinet d'Hardemare, Marlène Debiossat, Clémence André, Jean Boutonnat and 12 more

Abstract readComparative Study
In one paragraph

Article in European journal of nuclear medicine and molecular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Émilien N'GuessanUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Florian RaesUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Mitra AhmadiUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Sandrine BacotUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Laurent DumasUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Julien LeenhardtUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Amaury du Moulinet d'HardemareUniversity Grenoble Alpes, CNRS 5250, DCM, Grenoble, 38000, France.
Marlène DebiossatUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Clémence AndréUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Jean BoutonnatDépartement de Pathologie, University Grenoble Alpes, CHU Grenoble Alpes, Grenoble, 38000, France.
Jérôme DurivaultBiomedical Department, Centre Scientifique de Monaco, Monaco, 98000, Principality of Monaco.
Christopher MontemagnoBiomedical Department, Centre Scientifique de Monaco, Monaco, 98000, Principality of Monaco.
Jean-Luc LenormandUniversity Grenoble Alpes, CNRS 5525, TIMC-Tree, Grenoble, 38000, France.
Loïc DjaïlebUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Ulli KösterInstitut Laue-Langevin, Grenoble, 38000, France.
Michiel Van de VoordeSCK CEN, Nuclear Medical Applications, Mol, Belgium.
Stijn RamaekersSCK CEN, Nuclear Medical Applications, Mol, Belgium.
Ken VergutsSCK CEN, Nuclear Medical Applications, Mol, Belgium.
Catherine GhezziUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Pascale PerretUniversity Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Charlotte Lombardi *University Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France.
Alexis Broisat *University Grenoble Alpes, INSERM U1039, LRB, Grenoble, 38000, France. alexis.broisat@inserm.fr.ORCID 0000-0002-4265-8463

Funding

Agence Nationale de la Recherche ANR-11-INBS-0006Fondation ARC Fondation ARCHorizon 2020 101008571Institut National Du Cancer INCa PLBIO 2021-231Ligue Contre le Cancer LNCC - Comité de l'Isère - 2023
6 · The paper itself

Abstract

purposeMesothelin (MSLN), a 40 kDa glycoprotein normally confined to mesothelial cells, is overexpressed in several malignancies, including triple-negative breast cancer (TNBC). The anti-mesothelin single-domain antibody (sdAb, or “nanobody®”) DOTA-A1K2, previously validated for positron emission tomography (PET) imaging using site-specific 68Ga radiolabeling, may also serve as a radio-theranostic agent when labeled with 177Lu. Moreover, 161Tb has recently been proposed as an alternative to 177Lu that might provide additional efficacy due to the emission of Auger electrons. The aim of this study was to evaluate in vitro and in vivo the therapeutic effect of [177Lu]Lu-DOTA-A1K2 and [161Tb]Tb-DOTA-A1K2.

methodsBiodistribution was assessed in mice from 1 to 168 h post-injection. Therapeutic efficacy was tested using MDA-MB-231 TNBC cells transfected or not with MSLN. Clonogenic assays were performed after 24 h incubation with either radiotracer. In vivo, efficacy was evaluated over 9 weeks after a single intravenous injection of 2, 5, 10, or 20 MBq.

resultsDOTA-A1K2 was successfully radiolabeled with both isotopes with RCP > 95%. In vitro, [161Tb]Tb-DOTA-A1K2 was significantly more potent than [177Lu]Lu-DOTA-A1K2 in inhibiting colony formation (p < 0.01). In vivo in mice, the radiotracers exhibited similar biodistribution profiles. The administration of 5, 10 or 20 MBq of either [177Lu]Lu-DOTA-A1K2 or [161Tb]Tb-DOTA-A1K2 inhibited tumor growth compared to controls (p < 0.01 vs. vehicle), while no effect was observed at 2 MBq (p = NS). However, no differences in efficacy were observed between the two isotopes at any dose.

conclusionsThis work provides the first sdAb-based theranostic approach targeting mesothelin-positive tumors. In vivo in mice, both [177Lu]Lu-DOTA-A1K2 and [161Tb]Tb-DOTA-A1K2 accumulated in tumors. In vivo efficacy was found to be comparable, despite the superior in vitro efficacy of 161Tb. Further studies are warranted to clarify this discrepancy, which could potentially result from mesothelin shedding that prevents Auger electrons from reaching tumor cells.

Indexed as

GPI-Linked ProteinsLutetiumRadioisotopesTerbiumTheranostic NanomedicineTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleHumansMesothelinMiceTissue DistributionGPI-Linked ProteinsLutetiumLutetium-177MesothelinMSLN protein, humanMsln protein, mouseRadioisotopesTerbiumLutetium-177MesothelinRadio-ligand therapySdAbTerbium-161Triple negative breast cancer

Identifiers

PMID41454065
PMCPMC13121286

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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.