Nuclear Engineering Colloquium: Tara Mastren
Title: "The Production and Application of Radionuclides for the Treatment of Cancer"
Clinicians rely on nuclear medicine for the treatment of numerous diseases impacting millions of patients annually. Recently, targeted radiotherapy (TR) has been successfully advanced with the US FDA approval of several radionuclide-based drugs. Several types of radioactive emissions are of interest to therapy such as alpha, beta and auger electrons. The linear energy transfer (LET) of these particles to the surrounding tissue results in free radical production and direct damage to the DNA in cancer cells resulting in cell death. The two projects I will focus on today are the reactor production of 161Tb and the use of 225Ac radiolabeled nanoparticles for the treatment of neuroendocrine tumors.
We are currently working on producing Tb-161 (β-, 6.9 d), an isotope of interest due to its decay via the emission of both Auger and Beta particles, in the University of Utah TRIGA reactor using the indirect method: 160Gd(n,γ)161Gd(β-, 3.66m)161Tb reaction. As neighboring lanthanides are notoriously difficult to separate, we are investigating the feasibility of an in situ Szilard-Chalmers method employing a column in the center of the reactor to perform the initial separation of 161Tb from the target material. Additionally, we are developing methods to tune the energy spectrum of our reactor to obtain optimal yields of our product.
Actinium-225 has a 10 day half live and decays with the emission of four alpha particles and two beta particles. Recently, the use of 225Ac labeled peptides for the treatment of prostate cancer resulted in two patients with stage IV prostate cancer to go into remission. The use of a chelate to hold 225Ac is ineffective as the energy resulting from the decay of 225Ac to its first daughter 221Fr causes the bonds between the chelate and 225Ac to break. One way to mitigate this issue is to encompass the 225Ac into a nanoparticle, in particular silica nanoparticle. Silica nanoparticles are attractive materials for nuclear medicine applications due to their ability to bind heavy metal ions, low cost, and biological inertness. 89Zr, a PET radionuclide, can also be incorporated into the nanoparticles to create a theranositc agent. Additionally, silica nanoparticles can be easily functionalized with peptides allowing specific targeting of the tumor site. Octreotate is a peptide that targets the somatostatin receptor on neuroendocrine tumors (NETs). The incorporation of 225Ac and 89Zr into silica nanoparticles functionalized with octreotate would result in a theranostic agent for the treatment of NETs.
Tara Mastren is an Assistant Professor in the Nuclear Engineering Program at the University of Utah. She obtained her PhD in Nuclear and Radiochemistry at Washington University in St. Louis in December 2014. She then worked in the Radiology Department at the University of Texas Southwestern Medical School as a postdoctoral researcher. In May 2016 she joined Los Alamos National Laboratory, for her second postdoc, in their Isotope Production Program. Mastren’s interests are focused on the production and use of radionuclides for the targeted treatment of cancer and other diseases.
Wednesday, January 22 at 1:30pm to 2:30pm
Nuclear Engineering Building, 302
1412 Circle Drive Knoxville TN 37996