PD07-08: Fibroblast activation protein-specific MRI provides improved tumour mapping in an orthotopic model of prostate cancer compared to prostate specific membrane antigen

Nicole Dmochowska*, Valentina Milanova, Anil Shetty, Adelaide, Australia, Ramesh Mukkamala, Lafayette , IN, Madduri Srinivasarao, Lafayette, IN, Eric Walser, Galveston, TX, Phil Low, Lafayette, IN, Benjamin Thierry, Adelaide, Australia

Introduction: MRI guided focal therapies of prostate cancer have the potential to reduce treatment related side effects without sacrificing oncological outcomes. Molecular MRI with agents targeted to tumour tissues enhances tumour margin detection and consequently treatment guidance/planning. Prostate specific membrane antigen (PSMA) expression is currently the gold standard for molecular imaging of prostate cancer. Fibroblast activation protein (FAP) is an extracellular transmembrane protein expressed on cells of the tumour microenvironment, particularly in stromal and vascular components. FAP has been gaining momentum as a pan-cancer marker (DOI: 10.2967/jnumed.119.227967) as its overexpression often correlates with cancer severity, including in prostate cancer (DOI: 10.1371/journal.pone.0116683) and has been found to be negligibly expressed in healthy tissue. Our objective was to compare MRI contrast of PSMA-targeting and FAP-targeting magnetic nanoparticles (MNPs) in an orthotopic murine model of prostate cancer.

Methods: Control (no ligand), FAP and PSMA-targeted MNPs were prepared with modification of an MRI agent (FerroTrace, Ferronova) currently undergoing a phase 1 clinical trial. In vitro binding was evaluated in PSMA and FAP positive cell lines. To form orthotopic tumours, LNCaP cells (PSMA+ human prostate cancer) were injected into the prostate. After 4-6 weeks of tumour growth, mice underwent 16.4T T2-weighted 3D MRI 24 hours after intravenous injection of contrast agents. Enhancement of MRI contrast in tumours was quantified by determining the proportion of pixels with low signal intensity throughout regions of interest. Accumulation of MNPs in prostate tumours at 24 hours post injection was confirmed ex vivo by Prussian blue staining.

Results: PSMA and FAP-MNPs demonstrated specific binding in vitro. MRI contrast of tumours was increased in FAP (p < 0.001) and PSMA-MNPs (p < 0.05) but not control MNPs (p>0.05), relative to orthotopic tumours with no injected MNPs. FAP-MNPs provided increased contrast relative to PSMA-MNPs (~10% enhancement, p<0.05). Increased accumulation of FAP-MNPs in prostate tumours was observed on tissue sections compared to PSMA-MNPs. Control-MNPs showed minimal tumour accumulation.

Conclusions: These results suggest that FAP-targeting MNPs could enhance the MRI of prostate tumours and assist in the delivery of precise focal treatment.

Source of Funding: NHMRC Development Grant 1158755