Enhancing MRI of prostate cancer using PSMA-targeting iron oxide magnetic nanoparticles

Tse, B.W.C., Cowin, G.J., Soekmadji, C., Jovanovic, L., Vasireddy, R., Ling, M.T., Liu, M., Kharti, A., Thierry, B., & Russell, P.J. (2014) Enhancing MRI of prostate cancer using PSMA-targeting iron oxide magnetic nanoparticles. In 67th Annual Scientific Meeting of the Urological Society of Australia and New Zealand (USANZ 2014), 16–19 March 2014, Brisbane, Qld.

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Abstract

Introduction

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.

Materials and 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.

Conclusions

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: 77852
Item Type: Conference Item (Presentation)
Refereed: Yes
Additional Information: Published in BJU International, Special Issue: Abstracts of the Urological Society of Australia and New Zealand, 67th Annual Scientific Meeting, Brisbane, Australia, 16–19 March 2014 Volume 113, Issue Supplement S4, pages 51–137, March 2014
Additional URLs:
Keywords: MRI, Prostate cancer, imaging, PSMA-targeting, iron oxide magnetic nanoparticles
DOI: 10.1111/bju.12619
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Radiology and Organ Imaging (110320)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Diagnosis (111202)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Molecular Targets (111207)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 The Author(s)
Deposited On: 21 Oct 2014 01:10
Last Modified: 30 Nov 2015 22:25

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