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Article

In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe

by
Stavros Melemenidis
1,
James C. Knight
2,
Veerle Kersemans
3,
Francisco Perez-Balderas
4,
Niloufar Zarghami
5,
Manuel Sarmiento Soto
6,
Bart Cornelissen
7,
Ruth J. Muschel
5 and
Nicola R. Sibson
5,*
1
Department of Radiation Oncology, Stanford School of Medicine, Cancer Institute, Stanford University, Stanford, CA 94305, USA
2
School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
3
Clinical Nuclear Medicine Imaging, Siemens Healthineers, 2595 BN The Hague, The Netherlands
4
CureVac, AG. Paul-Ehrlich-Str. 15, 72076 Tubingen, Germany
5
Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK
6
Department of Biochemistry and Molecular Biology, University of Seville, 41004 Seville, Spain
7
Department of Nuclear Medicine, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(13), 7160; https://doi.org/10.3390/ijms25137160
Submission received: 28 May 2024 / Revised: 21 June 2024 / Accepted: 26 June 2024 / Published: 28 June 2024
(This article belongs to the Special Issue Molecular Research on Cancer and Molecular Imaging)
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Abstract

Current clinical diagnostic imaging methods for lung metastases are sensitive only to large tumours (1–2 mm cross-sectional diameter), and early detection can dramatically improve treatment. We have previously demonstrated that an antibody-targeted MRI contrast agent based on microparticles of iron oxide (MPIO; 1 μm diameter) enables the imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Using a mouse model of lung metastasis, upregulation of endothelial VCAM-1 expression was demonstrated in micrometastasis-associated vessels but not in normal lung tissue, and binding of VCAM-MPIO to these vessels was evident histologically. Owing to the lack of proton MRI signals in the lungs, we modified the VCAM-MPIO to include zirconium-89 (89Zr, t1/2 = 78.4 h) in order to allow the in vivo detection of lung metastases by positron emission tomography (PET). Using this new agent (89Zr-DFO-VCAM-MPIO), it was possible to detect the presence of micrometastases within the lung in vivo from ca. 140 μm in diameter. Histological analysis combined with autoradiography confirmed the specific binding of the agent to the VCAM-1 expressing vasculature at the sites of pulmonary micrometastases. By retaining the original VCAM-MPIO as the basis for this new molecular contrast agent, we have created a dual-modality (PET/MRI) agent for the concurrent detection of lung and brain micrometastases.
Keywords: micrometastasis; early detection; microparticles of iron oxide (MPIO); vascular cell adhesion molecule-1 (VCAM-1); dual modality (PET/MRI) micrometastasis; early detection; microparticles of iron oxide (MPIO); vascular cell adhesion molecule-1 (VCAM-1); dual modality (PET/MRI)

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MDPI and ACS Style

Melemenidis, S.; Knight, J.C.; Kersemans, V.; Perez-Balderas, F.; Zarghami, N.; Soto, M.S.; Cornelissen, B.; Muschel, R.J.; Sibson, N.R. In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe. Int. J. Mol. Sci. 2024, 25, 7160. https://doi.org/10.3390/ijms25137160

AMA Style

Melemenidis S, Knight JC, Kersemans V, Perez-Balderas F, Zarghami N, Soto MS, Cornelissen B, Muschel RJ, Sibson NR. In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe. International Journal of Molecular Sciences. 2024; 25(13):7160. https://doi.org/10.3390/ijms25137160

Chicago/Turabian Style

Melemenidis, Stavros, James C. Knight, Veerle Kersemans, Francisco Perez-Balderas, Niloufar Zarghami, Manuel Sarmiento Soto, Bart Cornelissen, Ruth J. Muschel, and Nicola R. Sibson. 2024. "In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe" International Journal of Molecular Sciences 25, no. 13: 7160. https://doi.org/10.3390/ijms25137160

APA Style

Melemenidis, S., Knight, J. C., Kersemans, V., Perez-Balderas, F., Zarghami, N., Soto, M. S., Cornelissen, B., Muschel, R. J., & Sibson, N. R. (2024). In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe. International Journal of Molecular Sciences, 25(13), 7160. https://doi.org/10.3390/ijms25137160

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