¶¡ÏãÔ°AV

Novel chelators and isotopes for targeted radionuclide therapy

TRIUMF Life Sciences Division maintains a strong medical isotope and radiopharmaceutical production and development capability enabled by the unique infrastructures, including four cyclotrons and deep expertise. The program supports local and international users conducting high-impact research and cutting-edge new technologies in nuclear medicine that can potentially revolutionize cancer treatment.

One of our major efforts is to develop novel radionuclides, chelates and radiopharmaceuticals for cancer theranostics (imaging + therapy), inspired by significant clinical efficacy of ²²⁵Ac targeted radionuclide therapy. The radiopharmaceuticals under development in our labs have successfully demonstrated effectiveness in preclinical evaluations.  We are looking for prospective graduate students to join this effort.  She/He will investigate radionuclide production, chelator synthesis, and radiolabelling and participate in the in vitro and in vivo evaluations.  We have the following thesis projects to offer:

• Production and separation of radiolanthanides (^132/135La, ¹⁴¹Ce, ¹⁶⁵Er etc.). Radiolanthanides provide a rich pool of medical relevant radionuclides for alpha-, beta-, Auger therapy, or SPECT, PET imaging.  For many radiolanthanides, their production methods are largely under-explored. Providing high purity isotope is the critical first step to realize their potential.
• Develop Tb radiopharmaceuticals. Tb isotopes are considered to be the ‘Swiss knives’ in nuclear medicine, because four medical relevant Tb isotopes: ¹⁴⁹Tb (alpha therapy), ¹⁵²Tb (PET imaging), ¹⁵⁵Tb (SPECT imaging), ¹⁶¹Tb (beta therapy) provide options for all major nuclear medicine modalities, enabling theranostics (therapy + imaging) using chemically identical compounds. Collaborating with SCK CEN (Belgium), we are one of the few facilities that have access to all four isotopes and the opportunity to develop novel Tb radiopharmaceuticals.
• Develop theranostics radiopharmaceuticals with alpha-emitters. ²²⁵Ac and ²²⁷Th are powerful alpha-emitters for cancer treatment.  One obstacle for their clinical application is to find a well-matched imaging companion for diagnosing and monitoring. We are looking into developing novel chelators that can stably coordinate ²²⁵Ac or ²²⁷Th and an imaging isotope.

Radiopharmaceutical development requires experts in targetry, radionuclide production, radiopharmaceutical production, preclinical evaluations, and clinical oncology to work together.  With recent surge of therapeutic isotopes, highly qualified personnel with broad knowledge and techniques in multiple fields are in high demand. In this program, students will have the opportunities to acquire the knowledge and techniques of the following areas: At radionuclide front: isotope production and radiochemical purification using different methods, and characterization. At the chemistry front: organic and inorganic synthesis, bioconjugation, radiolabeling and characterization. At the biology front: cancer biology, cell culture, tumour inoculation, animal husbandry, and in vivo imaging, biodistribution and therapy.

The successful candidate will be a chemistry student with lab experience. Experience with organic synthesis and characterization (NMR, MS) is desired. Experience with other analytical methods (HPLC, UV) and communication skills will be considered an asset. Attention to details, team-oriented, and self-management are desired qualities.  Applicants need to meet ¶¡ÏãÔ°AV graduate school admission requirements.

Contact:

• Dr. Hua Yang, hyang@triumf.ca
• Dr. Valery Radchenko, vradchenko@triumf.ca

Thermal Separation of Volatile Rare Isotopes from Irradiated Target Materials

Nuclear medicine research on radiotherapeutic methods like radioimmunotherapy, targeted alpha particle therapy and complementary imaging techniques are hampered by the limited availability of extremely rare and relatively short-lived isotopes such as ^209,211At, ²²⁵Ac, ^223,224Ra, ²¹³Bi or ²¹²Pb. They can be produced by irradiating actinide targets with high-energy particles such as the intense 500 MeV proton beam from the world’s largest cyclotron at TRIUMF. A wide range of radioisotopes is generated by this process. Separating and purifying isotopes of interest for nuclear medicine research is a challenge. Typically, a purely chemical separation is performed by dissolving the target including its radioactive inventory. An alterative to this method, which requires complex radiochemistry and produces a lot of radioactive waste, is to use thermal chromatography to separate species of varying volatility from an irradiated target. The investigation of thermodynamic and chemical properties that govern the diffusion and effusion of volatile species in this context offers opportunities for a number of thesis projects.

Interested graduate students will have the opportunity to obtain knowledge and receive training on the following subjects:

• Working in a controlled radiation area: The student will receive WHIMS, laboratory  and radiation safety training and must obtain the status of a nuclear energy worker.
• Experimental setup: Includes design, assembly and integration of the components and the data acquisition system. The student will gain knowledge about vacuum systems, mass spectrometry and data processing.
• Measurements: The student will perform measurements and modifications of the experimental setup if necessary, learning how to organize, document and execute experiments independently and in a team.
• Online experiments: The goal of the project is to experiment with radioactive samples obtained from ion beam collections or irradiations. The candidate will learn about nuclear spectroscopy techniques and characterize rare isotope beams by their radioactive decay signatures.
• Data analysis: The candidate will have to put experimental results into a theoretical context, describing thermodynamics and chemistry with appropriate models and/or simulations.

Two specific thesis projects are offered:

1. Investigation of the thermal separation of astatine and radon isotopes from actinide targets.

The focus on this research project is ²¹¹At, a promising candidate for cancer therapy, and its precursor ²¹¹Rn. The release properties of astatine and radon from actinide targets as a function of temperature need to be investigated and understood. Developing an efficient method and designing a suitable apparatus to separate and/or trap these isotopes is the ultimate goal of the project.

2. Investigation of the thermal separation of radium and actinium isotopes.

²²³Ra and ²²⁵Ac are promising isotopes for cancer therapy. Radium and actinium become volatile only at very high temperatures. The main goal of this project is the development of a method for the efficient separation from refractory actinide targets, requiring the investigation of thermodynamic and chemical processes at high temperatures using a vacuum furnace.

For further information and inquiries, please contact

Prof. Corina Andreoiu, ¶¡ÏãÔ°AV, corina_andreoiu@sfu.ca and Dr. Peter Kunz, TRIUMF pkunz@triumf.ca