TY - JOUR
T1 - Nanoparticles targeted to fibroblast activation protein outperform PSMA for MRI delineation of primary prostate tumors
AU - Dmochowska, Nicole
AU - Milanova, Valentina
AU - Mukkamala, Ramesh
AU - Chow, Kwok Keung
AU - Pham, Nguyen T. H.
AU - Srinivasarao, Madduri
AU - Ebert, Lisa M.
AU - Stait-Gardner, Timothy
AU - Le, Hien
AU - Shetty, Anil
AU - Nelson, Melanie
AU - Low, Philip S.
AU - Thierry, Benjamin
PY - 2023/5/24
Y1 - 2023/5/24
N2 - 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.
AB - 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.
UR - https://hdl.handle.net/1959.7/uws:72092
U2 - 10.1002/smll.202204956
DO - 10.1002/smll.202204956
M3 - Article
SN - 1613-6829
SN - 1613-6810
VL - 19
JO - Small
JF - Small
IS - 21
M1 - 2204956
ER -