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Brief Report

99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma

by
Christopher Montemagno
1,2,
Shamir Cassim
2,
Dimitry Trichanh
1,
Clara Savary
3,
Jacques Pouyssegur
2,4,
Gilles Pagès
2,4,
Daniel Fagret
1,
Alexis Broisat
1,* and
Catherine Ghezzi
1
1
LRB, CHU Grenoble Alpes, INSERM U1039, Université Grenoble Alpes, 38000 Grenoble, France
2
Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco
3
IGDR (Institut de génétique et développement de Rennes), UMR CNRS 6290, Université de Rennes, 35000 Rennes, France
4
Institute for Research on Cancer and Aging of Nice, Centre Antoine Lacassagne, CNRS UMR 7284, INSERM U1081, Université Côte d’Azur, 06200 Nice, France
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1531; https://doi.org/10.3390/cancers11101531
Submission received: 20 September 2019 / Revised: 8 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Role of Medical Imaging in Cancers)
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Abstract

Mesothelin is a membrane-associated protein overexpressed in pancreatic ductal adenocarcinoma (PDAC). Some mesothelin-targeted therapies are in clinical development but the identification of patients eligible for such therapies is still challenging. The objective of this study was to perform the imaging of mesothelin in mice models of PDAC with a technetium-labeled anti-mesothelin single-domain antibody (99mTc-A1). Methods: The Cancer Genomic Atlas (TCGA) database was used to determine the prognostic role of mesothelin in PDAC. 99mTc-A1 was evaluated both in vitro in PDAC cells (SW1990 and AsPC-1) and in vivo in an experimental model of mesothelin-expressing PDAC (AsPC-1) in mice. Results: TCGA analysis showed that PDAC patients with high mesothelin expression had a shorter overall survival (P = 0.00066). The binding of 99mTc-A1 was 2.1-fold greater in high-mesothelin-expressing AsPC-1 cells when compared to moderate-mesothelin-expressing SW1990 cells (p < 0.05). In vivo, the 99mTc-A1 uptake was 3.5-fold higher in AsPC-1-derived tumors as compared to a technetium-labeled irrelevant antibody (99mTc-Ctl) (p < 0.01). Conclusions: 99mTc-A1 accurately allows imaging of mesothelin-expressing experimental PDAC tumors. Our experiments paved the way for the development of a companion test for mesothelin-targeted therapies.
Keywords: PDAC; Mesothelin; noninvasive imaging PDAC; Mesothelin; noninvasive imaging

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MDPI and ACS Style

Montemagno, C.; Cassim, S.; Trichanh, D.; Savary, C.; Pouyssegur, J.; Pagès, G.; Fagret, D.; Broisat, A.; Ghezzi, C. 99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma. Cancers 2019, 11, 1531. https://doi.org/10.3390/cancers11101531

AMA Style

Montemagno C, Cassim S, Trichanh D, Savary C, Pouyssegur J, Pagès G, Fagret D, Broisat A, Ghezzi C. 99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma. Cancers. 2019; 11(10):1531. https://doi.org/10.3390/cancers11101531

Chicago/Turabian Style

Montemagno, Christopher, Shamir Cassim, Dimitry Trichanh, Clara Savary, Jacques Pouyssegur, Gilles Pagès, Daniel Fagret, Alexis Broisat, and Catherine Ghezzi. 2019. "99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma" Cancers 11, no. 10: 1531. https://doi.org/10.3390/cancers11101531

APA Style

Montemagno, C., Cassim, S., Trichanh, D., Savary, C., Pouyssegur, J., Pagès, G., Fagret, D., Broisat, A., & Ghezzi, C. (2019). 99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma. Cancers, 11(10), 1531. https://doi.org/10.3390/cancers11101531

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