Fibroblast Activation Protein-Specific MRI Enhances Tumor Mapping in Prostate Cancer

Fibroblast activation protein (FAP)-targeting magnetic nanoparticles (MNPs) enhanced magnetic resonance imaging (MRI) of prostate tumors may support delivery of more precise focal treatment in prostate cancer, according to a study presented by Nicole Dmochowska, PhD, of the University of South Australia, at the 2022 American Urological Association Annual Meeting.

Focal therapies for prostate cancer, when guided by MRI, feature the potential to reduce side effects related to therapy without compromising clinical outcomes. The use of molecular MRI with targeted agents directed to tumor tissues can enhance tumor margin detection and inform treatment decision-making.

According to Dr. Dmochowska, the current “gold standard” for the molecular imaging of prostate cancer is prostate specific membrane antigen (PSMA) expression. Additionally, FAP, an extracellular transmembrane protein that is expressed on cells in the tumor microenvironment, has increasingly shown value as a pan-cancer marker, given the overexpression of FAP tends to be associated with the severity of prostate cancer.

In the most recent study, Dr. Dmochowska and colleagues compared MRI contrast of PSMA-targeting and FAP-targeting magnetic nanoparticles (MNPs) in an animal model of prostate cancer.

The study investigators prepared was a control (no ligand), FAP, and PSMA-targeted MNPs with modification of an investigational MRI agent. The researchers assessed in vitro binding in PSMA- and FAP-positive cell lines. Additionally, the investigators injected LNCaP cells (PSMA+ human prostate cancer) into the prostate to form orthotopic tumors.

Following an up to 6-week tumor growth phase, the researchers subjected mice to 16.4T T2-weighted 3D MRI approximately 24 hours following intravenous injection of contrast agents. To quantify the enhancement of MRI contrast in the evaluated tumors, the investigators determined the proportion of pixels featuring low signal intensity throughout various regions of interest. Prussian blue staining was used to confirm ex vivo the accumulation of MNPs in prostate tumors at 24 hours following injection.

According to the presented findings by Dr. Dmochowska, the PSMA and FAP-MNPs showed specific in vitro binding. In addition, the MRI contrast of tumors significantly increased with both FAP (p<0.001) and PSMA-MNPs (p<0.05), but no such increase was observed in control MNPs (p>0.05) compared with orthotopic tumors with no injected MNPs.

In addition, the FAP-MNPs offered increased contrast compared with PSMA-MNPs, which featured an approximately 10% enhancement (p<0.05). There was increased accumulation of FAP-MNPs in prostate tumors compared with PSMA-MNPs. In control MNPs, only minimal tumor accumulation was observed.