ERF: Uncovering the cellular mechanisms that limit clinical application of PRRT

Year: 2020
Institution: represented by Klinikum rechts der Isar, Technical University Munich
Country: Germany
Award Type: Collaborative
NET Type: Multiple
Science Type: Translational

General Description

Tara Mastren, PhD, University of Utah, will study a novel theranostic agent that could increase precision in neuroendocrine tumor treatment. Mastren’s laboratory research project, Functionalized Silica Nanoparticles: Development of a Combined PET and TAT Theranostic Agent for Neuroendocrine Tumors, will try to resolve some of the inherent challenges of targeted alpha therapy.

  • When radionuclides decay via the emission of an alpha particle, they release energy that can harm healthy cells.
  • Alpha particles are hard to monitor using a SPECT scan.
  • Radionuclides, such as Actinium-225 (Ac-225), decay through a chain of short-lived intermediates before reaching a stable element. Keeping these intermediates near the cancer cells is imperative to maximize the dose to diseased cells while minimizing the dose to healthy cells.

Targeted alpha therapy solutions to be studied

Using a methodological approach, Mastren and her colleagues at the University of Utah will try to overcome these challenges and develop a nanoparticle-based therapeutic agent that can be detected in SPECT scans with some modifications.

  • Mastren will place an alpha-emitting radionuclide Ac-225 in a silica nanoparticle, which could help to contain radioactive daughters produced during decay, to reduce healthy cell exposure and increase cancer cell damage.
  • Mastren will insert a radionuclide (Zr-89) into the nanoparticle that can be detected by scan cameras to support treatment planning and monitoring.
    The nanoparticle system will then be tested in laboratory models for stability.

This theranostic agent (Ac-225/Zr-89-octreotate silica nanoparticles) is intended to be delivered using Peptide Receptor Radionuclide Therapy (PRRT). Promising results from this pilot study, which explores the feasibility of this PET/TAT agent, could pave the way for pre-clinical studies as a next step.