Terbium Isotopes as Radiopharmaceuticals: Alpha Therapy and PET Imaging

Emily Paige Abel, NSCL
Thursday, Nov 16, 11:00 AM - Research Discussion
NSCL Lecture Hall 1200

Abstract:  As the second leading cause of mortality in the U.S. in 2015, cancer was responsible for 22% of deaths reported [1]. One treatment option is targeted internal radiation therapy with alpha or beta emitting radionuclides. This ionizing radiation can destroy the DNA of a cancer cell, interfering with cell replication. Alpha particles demonstrate a linear energy transfer of about 60-230 keV/µm compared to 0.1-1 keV/µm for beta particles, resulting in a shorter range and higher relative biological effectiveness for alpha particles [2]. While these effects are desirable for cancer treatment, alpha emitters are riddled with problems from undesirable half- lives to a lack of availability. Among the alpha emitters with suitable characteristics is 149Tb (t1/2 = 4.12 h, Eα = 3.937 MeV, Iα = 16.7 %). However, this isotope is currently difficult to make in sufficient quantities to carry out large-scale preclinical research. Three different production methods are available: light ion reactions, heavy ion reactions, and proton spallation [3,4]. In 2014, a sample of 149Tb was collected from a proton spallation reaction on a tantalum target at ISOLDE to conduct a small preclinical test using 149Tb-DOTA-folate. This study showed promising results as tumor growth was delayed and survival time increased in mice treated with this radiotherapy compared to control mice [5]. In addition to the therapeutic effects of 149Tb, this isotope forms a theranostic radionuclide pair with 152Tb (t1/2 = 17.5 h, Eβ+ = 1.14 MeV, Iβ+ = 20.3 %). In a recent clinical study, 152Tb-DOTATOC was used to produce PET images of a patient with metastatic neuroendocrine cancer. The images were comparable to those of 68Ga, a clinically used positron emitter [6]. These studies show promise for effective therapy and imaging of cancer with the 149Tb and 152Tb theranostic pair. References: 1. National Center for Health Statistics. Health, United States, 2016: With Chartbook on Long- term Trends in Health. Hyattsville, MD. 2017. 2. M.W. Brechbiel. Dalton Trans. 43, 4918 (2007). 3. G.J. Beyer, J.J. Čomor, M. Dković, D. Soloviev, C. Tamburella, E. Hagebø, B. Allan, S.N. Dmitriev, N.G. Zaitseva, G.Ya. Starodub, et. al. Radiochim Acta. 90, 241 (2002). 4. B.J. Allen, G. Goozee, S. Sarkar, G. Beyer, C. Morel, A.P. Byrne. Appl Radiat Isotopes. 54, 53 (2001). 5. C. Müller, J. Reber, S. Haller, H. Dorrer, U. Köster, K. Johnston, K. Zhernosekov, A. Türler, R. Schibli. Pharmaceuticals. 7, 353 (2014). 6. R.P. Baum, A. Singh, M. BeneÅ¡ová, C. Vermeulen, S. Gnesin, U. Köster, K. Johnston, D. Müller, S. Senftleben, H.R. Kulkarni. Dalton T. (2017). (in press) doi: 10.1039/c7dt01936j.