Exploring Targeted Alpha Therapy for Neuroendocrine Tumors

Increasing Precision in Cancer Cell Death to Prevent Metastasis

In housework and lawn work, it is important to have the right tool for the job. When you want to remove dust out of the corners of the ceiling, you use a crevice tool, not a full-size vacuum cleaner head. Likewise, to cut the grass along a fence line, you reach for an edge trimmer.    

In principle, a neuroendocrine tumor (NET) treatment specialist sometimes needs a precision tool to target lingering cancer cells in the tissue surrounding a neuroendocrine tumor.

The Neuroendocrine Tumor Research Foundation (NETRF) will fund a new grant to Tara Mastren, PhD, University of Utah, to study a novel theranostic agent that could increase precision in neuroendocrine tumor treatment. This 2019 Nuclear Medicine Pilot Grant is offered in collaboration with the Education and Research Foundation for Nuclear Medicine and Imaging (ERF).

Eliminating all neuroendocrine cancer cells

Surgery removes neuroendocrine tumors as well as surrounding tissue that appears to be affected. Peptide Receptor Radionuclide Therapy (PRRT) with lutetium 177 dotatate (Lu-177) uses radioactive beta particles to target larger tumors. But beta particles are like a full-size vacuum cleaner head or a lawn mower; they carve a wide swath; they are not very precise. When a neuroendocrine tumor is in a vital organ like the lung or pancreas, it is important to preserve as much healthy tissue as possible. This requires pinpoint precision.  

“One of the problems we are trying to solve with our funding is the prevention of metastasis,” said Elyse Gellerman, Chief Executive Office, Neuroendocrine Tumor Research Foundation. “We want to improve the long-term outlook for people with NETs by supporting research to destroy every last trace of neuroendocrine cancer to reduce the risk of recurrence.”

Exploring targeted alpha therapy in neuroendocrine tumors

The Neuroendocrine Tumor Research Foundation is exploring the role alpha particles could play as a precision cancer-cell-killing tool through “Targeted Alpha Therapy” (TAT). Developing the technology, however, requires research and funding.

Challenges of alpha-particle therapy in NETs

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 (a CT scan that uses a radioactive tracer) as they do not travel far in the body and typically have weak gamma emissions that are below the sensitivity of SPECT cameras. (Doctors use SPECT scans during treatment to plan, monitor, and refine doses.)
  • 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.

It’s unclear whether this new theranostic agent will remain stable during use.

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.

Next steps

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. 

NETRF’s funding of neuroendocrine tumor research is made possible through generous donations from individuals and families committed to supporting a search for a cure to neuroendocrine cancer. 

The Education and Research Foundation for Nuclear Medicine and Molecular Imaging (ERF) secures, invests and distributes funding to support rigorously vetted physicians, scientists and technologists in the pursuit of advanced academic studies or breakthrough discoveries in the fields of nuclear medicine and molecular imaging.  ERF is the leading source of private philanthropic financial support focused exclusively on education and research programs in nuclear medicine and molecular imaging. To learn more, please visit us at www.mierf.org.