Development of PSMA-targeting nanoparticles for positron emitting tomography imaging in prostate cancer using animal models
Mentor: Georges El Fakhri, PhD (MGH)
The project will focus on using feraheme (FH) as a scaffold to develop PSMA-targeting nanoparticles (NPs) using a PSMA-inhibitor (PSMA-I) in order to better image prostate cancer. Click chemistry will be applied to synthesize the NP quickly and efficiently. Prostate cancer cells display a concentration of PSMA markers 1000x more concentrated on their membrane than non-cancerous prostate cells. Feraheme is an FDA-approved off-label nanoparticle that has very low toxicity and high non-specific cellular uptake, but when a PSMA-I is attached, tissue-specific targeting will be demonstrated by comparing non-specific uptake in PSMA(+) and PSMA(-) tumor cell lines. PSMA is expressed in both the prostate and the brain which allows the NP to target multiple organs. By attaching several targeting structures on the surface of the NP, the synergistic effect will give the FH-PSMA-I NP better diagnostic power in vivo. Eventually, further additions on the surface of the NP will add specificity and will allow subtyping of prostate cancers.
A) First, the prostate-specific membrane antigen inhibitor (PSMA-I) will be synthesized using click chemistry. B) The PSMA-I will then be anchored onto the surface of our nanoparticle Feraheme. C) In vitro cell line tests will test the toxicity and non-specific uptake of FH-PSMA-I in PSMA-positive and PSMA-negative prostate cancer cell lines. D) Once safety and non-specific uptake has been accounted for, the nanoparticle will be radiolabeled and injected into mice models. E) The mice models will be imaged over the course of a few days to determine the pharmacokinetics of the FH-PSMA-I nanoparticle. Source: