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

Lookup NU author(s): Dr James KnightORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

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, t_1/2 = 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.

Publication metadata

Author(s): Melemenidis S, Knight JC, Kersemans V, Perez-Balderas F, Zarghami N, Soto MS, Cornelissen B, Muschel RJ, Sibson NR

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2024

Volume: 25

Issue: 13

Print publication date: 01/07/2024

Online publication date: 28/06/2024

Acceptance date: 26/06/2024

Date deposited: 03/07/2024

ISSN (electronic): 1422-0067

Publisher: MDPI AG

URL: https://doi.org/10.3390/ijms25137160

DOI: 10.3390/ijms25137160

Data Access Statement: The datasets supporting the findings of the current study are available from the corresponding author upon request.

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