@article{d02d93c1d6484c23b15fcebf0a8aa27b,
title = "Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors",
abstract = "Accurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer. Magnetic resonance imaging (MRI) of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-linear accelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of >90% of epithelial carcinomas. Herein, the authors compare targeted MRI of prostate specific membrane antigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA-targeting iron oxide nanoparticles were prepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP-targeted MRI increased the proportion of tumor contrast-enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.",
keywords = "fibroblast activation proteins, iron oxide nanoparticles, magnetic resonance imaging, prostate cancer, prostate-specific membrane antigen, Humans, Male, Nanoparticles, Prostatic Neoplasms, Magnetic Resonance Imaging, Animals, Fibroblasts, Mice, Prostate",
author = "Nicole Dmochowska and Valentina Milanova and Ramesh Mukkamala and Chow, {Kwok Keung} and Pham, {Nguyen T.H.} and Madduri Srinivasarao and Ebert, {Lisa M.} and Timothy Stait-Gardner and Hien Le and Anil Shetty and Melanie Nelson and Low, {Philip S.} and Benjamin Thierry",
note = "Funding Information: N.D., V.M., N.P., R.M., M.N., P.L., and B.T. hold patents for FAP imaging technologies. B.T. is a founding member and shareholder of Ferronova Pty Ltd. N.D. and V.M. salaries are funded through Australian National Health and Medical Research Council grant 1158‐755 and each undertake duties involving research and development that contribute to Ferronova Pty Ltd. A.S. and M.N. are employees of Ferronova Pty Ltd. Funding Information: The authors acknowledge the facilities and scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at SAHMRI PIRL, the University of Western Sydney, and the University of Queensland. This research was supported by funding from an Australian National Health and Medical Research Council grant number 1158755 (B.T. as chief investigator A), and grants to L.E. from Tour de Cure, the Ray & Shirl Norman Cancer Research Trust, and the Mark Hughes Foundation. Funding Information: The authors acknowledge the facilities and scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at SAHMRI PIRL, the University of Western Sydney, and the University of Queensland. This research was supported by funding from an Australian National Health and Medical Research Council grant number 1158755 (B.T. as chief investigator A), and grants to L.E. from Tour de Cure, the Ray & Shirl Norman Cancer Research Trust, and the Mark Hughes Foundation. Open access publishing facilitated by University of South Australia, as part of the Wiley - University of South Australia agreement via the Council of Australian University Librarians. Publisher Copyright: {\textcopyright} 2023 The Authors. Small published by Wiley-VCH GmbH.",
year = "2023",
month = may,
day = "24",
doi = "10.1002/smll.202204956",
language = "English (US)",
volume = "19",
pages = "e2204956",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley",
number = "21",
}