Application of PSMA-targeting magnetic nanoparticles into MRI of prostate cancer

Tse, Brian, Cowin, Gary, Soekmadji, Carolina, Jovanovic, Lidija, Thierry, Benjamin, & Russell, Pamela (2013) Application of PSMA-targeting magnetic nanoparticles into MRI of prostate cancer. In Prostate Cancer World Congress and 14th Australasian Prostate Cancer Conference, 6–10 August 2013, Melbourne, Australia.

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Abstract

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Objective

Novel imaging techniques for prostate cancer (PCa) are required to improve staging and real-time assessment of therapeutic response. We performed preclinical evaluation of newly-developed, biocompatible magnetic nanoparticles (MNPs) conjugated with J591, an antibody specific for prostate specific membrane antigen (PSMA), to enhance magnetic resonance imaging (MRI) of PCa. PSMA is expressed on ∼90% of PCa, including those that are castrate-resistant, rendering it as a rational target for PCa imaging.

Methods

The specificity of J591 for PSMA was confirmed by flow cytometric analysis of several PCa cell lines of known PSMA status. MNPs were prepared, engineered to the appropriate size, labeled with DiR fluorophore, and their toxicity to a panel of PC cells was assessed by in vitro Alamar Blue assay. Immunohistochemistry, fluorescence microscopy and Prussian Blue staining (iron uptake) were used to evaluate PSMA specificity of J591-MNP conjugates. In vivo MRI studies (16.4T MRI system) were performed using live immunodeficient mice bearing orthotopic LNCaP xenografts and injected intravenously with J591-MNPs or MNPs alone.

Results

MNPs were non-toxic to PCa cells. J591-MNP conjugates showed no compromise in specificity of binding to PSMA+ cells and showed enhanced iron uptake compared with MNPs alone. In vivo, tumour targeting (significant MR image contrast) was evident in mice injected with J591-MNPs, but not MNPs alone. Resected tumours from targeted mice had an accumulation of MNPs, not seen in normal control prostate.

Conclusion

Application of PSMA-targeting MNPs into conventional MRI has potential to enhance PCa detection and localization in real-time, improving patient management.

Impact and interest:

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ID Code: 85247
Item Type: Conference Item (Other)
Refereed: No
Additional Information: Abstract published in BJU International Special Issue: Abstracts of the Prostate Cancer World Congress & 14th Australasian Prostate Cancer Conference, Melbourne, Australia, 6–10 August 2013, Volume 112, Issue Supplement S1, pages 34–35, August 2013
DOI: 10.1111/bju.12293
ISSN: 1464-410X
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 The Authors
Deposited On: 09 Jul 2015 22:33
Last Modified: 25 Jun 2017 02:01

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