PSMA-targeted AuNPs for MR guided radiotherapy and radiosensitization

Project: Research project

Project Details

Description

The Meade laboratory at Northwestern University has extensive synthetic chemistry experience, especially in the are of lanthanide probes and nanoparticles. We will use this expertise in conjunction with the Au-nanoparticle platform to synthesize a series of MR labeled and targeted prostate-specific membrane antigen (PSMA) contrast agents (PSMA-1-Au-GdNPs).
To accomplish our goals we will use recently developed Gd(III) chelates for improved MR contrast enhancement. Utilizing standard coupling techniques, we will bind high-relaxivity Gd(III) chelates to Au nanoparticle of varying size.
This PSMA marker is overexpressed on the vast majority of prostate cancers. Due to the complex nature of the probes, we will focus on the synthesis and characterization of the particle payloads, particle stability, and targeting efficiency. Initial studies will take advantage of Northwestern facilities for analyses such as Inductively Coupled Mass Spectrometry (ICP-MS) and Dynamic Light Scattering (DLS). Au-Nanoclusters will be synthesized as a result of preliminary data showing very high relaxivities can be achieved when Gd(III) is coupled to the Au.
Dr. Chad Haney is the Managing Director of Center for Advanced Molecular Imaging (CAMI) at Northwestern University and will acquire phantom image data on all the new modified agents. These techniques are crucial to optimizing Gd(III) loading and particle stability. It will be important to translate results from phantom data to in vivo imaging. CAMI has protocols in place with the Meade lab to optimize and characterize contrast agents. CAMI will establish optimal imaging parameters prior to radiation therapy studies. Utilizing the Chicago Biomedical Consortium memorandum of understanding, Dr. Haney will be able to supervise experiments at the University of Chicago. He has extensive experience in using small animal imaging to measure response to cancer treatment including radiation therapy.
StatusActive
Effective start/end date3/1/212/28/25

Funding

  • Case Western Reserve University (RES516065//1R01CA260847-01)
  • National Cancer Institute (RES516065//1R01CA260847-01)

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