Radiochemistry Laboratories

01 Overview
02 Radiochemistry Laboratories Science Highlights
03 How it Works

01 Overview

TRIUMF’s radiochemistry laboratories combine cutting-edge expertise in the research and production of radioisotopes and radiopharmaceuticals for use in nuclear medicine and the broader life sciences.

Radioisotopes are imaging molecules and therapeutic drugs whose active component is a short-lived radioactive isotope, also called a medical isotope or radiopharmaceutical. These are the core of nuclear medicine, the field of health care that uses radiation for therapy and medical imaging.

Every day, several hundred thousand patients world-wide have life-saving treatments and images using radiopharmaceuticals, including positron emission tomography (PET) and single-photon emission computerized tomography (SPECT) scans. Along with brain and bone imaging, radioisotopes are particularly used for diagnosing and treating heart disease and cancer, the two leading causes of death in North America.

The most widely used imaging radioisotope is technetium-99m (^99mTc) used in about 80% of all nuclear imaging. In Canada, about 7,000 patients a day have a ^99mTc scan, primarily for heart stress test and bone imaging. Currently, most ^99mTc is produced through an expensive process involving just several nuclear reactors for the entire global supply.

TRIUMF radiochemistry researchers have invented a ground-breaking small medical cyclotron-based, solid target system that enables the abundant, cost-effective production of ^99mTc. The technology is being commercialized by TRIUMF spin-off company ARTMS. The technology developed to produce ^99mTc has also been repurposed to produce other important medical isotopes like gallium-68 (⁶⁸Ga), copper-64 (⁶⁴Cu), and zirconium-89 (⁸⁹Zr).

Similarly, TRIUMF is a Canadian pioneer in the production of the carbon-11 (¹¹C) and fluorine-18 (¹⁸F), medical isotopes used in PET scanning, the most precise form of nuclear imaging.

Presently, nuclear medicine is experiencing a renaissance with research into new radiopharmaceuticals, including ones for personalized medicine combining specific targeted therapies in response to targeted diagnostic tests.

In TRIUMF’s radiochemistry laboratories, teams of physicists, chemists and engineers collaborate with a diverse, international network of clinical and life scientists to turn fundamental research into new radiopharmaceuticals. The radiochemistry laboratories also support long-standing partnerships with British Columbian and Canadian nuclear medicine organizations, including UBC Hospital and BC Cancer.

02 Radiochemistry Laboratories Science Highlights

New aqueous fluorination techniques

New aqueous fluorination techniques: ¹⁸F is a key isotope for the production of many radiopharmaceuticals. For decades, the addition of ¹⁸F to radiopharmaceutical precursors required harsh (high temperature, anhydrous) chemical conditions in order to provide adequate yields of the desired products. These conditions typically degrade more sensitive biomolecules, such as antibodies, peptides and proteins. Over the past 5 years, TRIUMF has worked collaboratively with scientists at the University of British Columbia and Simon Fraser University to develop two novel aqueous fluorination methods. Efforts with Dr. David Perrin (UBC, Chemistry) enabled the development of aqueous aryltrifuloroborate chemistry for rapid, 1-step incorporation of ¹⁸F onto peptides and other biomolecules; while those with Dr. Robert Britton have resulted in a novel method that uses a light-activated catalyst to place fluorine atoms on very specific locations of certain amino acids. These methods give radiopharmaceutical chemists new tools by which to produce radiopharmaceuticals that have been, until now, inaccessible or too difficult to produce.

bio-betaNMR: A new tool to understand biology at the molecular level

bio-betaNMR: A new tool to understand biology at the molecular level Although bNMR has been applied to nuclear physics and condensed matter for the past five decades, its application to biology, wet chemistry, and medicine are still fairy uncommon, mainly due to technical difficulties of maintaining liquid solutions under vacuum. Over the past three years, TRIUMF has not only pioneered technology that overcomes that barrier, but also carried out first experiments on liquids and biological samples, moving from proof-of-feasibility to first applications. In April 2017, we recorded the first-ever bNMR signals originating from oxygen and nitrogen coordinating Mg²⁺in typical Mg complexes, illustrating that bNMR can discriminate between different structures. In July 2018, we carried out first bNMR measurements on Mg coordination to ATP. This achievement marks a milestone in applications of bNMR into biologically-relevant samples and opens new opportunities in the fields of wet chemistry, biology, and medicine.

Novel accelerator target technology for improved production of medical isotopes

Novel accelerator target technology for improved production of medical isotopes: Historically, research within TRIUMF’s Life Science division has focused on the world’s more common PET isotopes: ¹¹C, ¹³N and ¹⁸F. However, through new target development in recent years, this list has been dramatically expanded to include new isotopes through new target development: ⁶⁸Ga, ⁴⁴Sc, ⁸⁶Y, ⁸⁹Zr, ¹⁹²Ir, ⁵²Mn, ^61,64Cu, ^99mTc and ¹¹⁹Sb. One of these new target systems is the so-called solution target, modelled after the remotely-controlled ¹⁸F production process currently used in medical cyclotrons. In lieu of a traditional solid target station, this technique allows for the irradiation of solutions (for example: nitrate solutions of metals of interest) in a cost-efficient, simple, and safe manner.

Novel radiopharmaceuticals for imaging unique metabolic pathways in cancer

Novel radiopharmaceuticals for imaging unique metabolic pathways in cancer: Amino acids play an important role in many biological processes, serving a key role in protein synthesis and as substrates for important intermediary metabolic processes and cell signaling pathways. This makes them prime candidates for templates for new medical imaging probes – substances that can be used to diagnose and track the development of diseases. To this end, TRIUMF has developed novel tracers toward two molecular systems: x_C- and LAT1. System x_C- helps to maintain homeostasis via antioxidant/free radical management at the cellular level, while the LAT1 transporter is an important component of protein synthesis in cells. TRIUMF has developed ¹⁸F-fluoroaminosuberic acid (¹⁸FASu) as a specific positron-emitting substrate of system x_C-; and via collaborative efforts with scientists at SFU, a series of leucine-like radiolabeled amino acids as substrates of LAT1. Studies are ongoing to establish the utility of both tracers in the detection, staging and treatment monitoring of a number of different cancers.

Redefining the global isotope supply philosophy

Redefining the global isotope supply philosophy: In 2009, the world was recovering from widespread shortages of ^99mTc - an isotope used in ~40 million nuclear medicine scans around the world every year - when the Canadian federal government announced the imminent cessation of isotope production activities at the Chalk River reactor. In response, TRIUMF (along with BC Cancer, the Centre for Probe Development and Commercialization, and Lawson Health Research) teamed together to develop a novel, high-powered target hardware solution capable of enabling the production of commercial-scale quantities of ^99mTc using local, hospital-based cyclotrons. This technology has been licensed to a new spin-off company, ARTMS Products, Inc., which obtained US$3M in venture funding from Quark Ventures in December 2017. Cyclotron-produced ^99mTc is now being implemented in the United Kingdom, with additional jurisdictions soon to follow. This same hardware has since been adapted to allow for the production of ⁶⁸Ga, ⁶⁴Cu, ⁸⁹Zr and other isotopes of interest.

03 How it Works

Based in an annex of the Meson Hall, the TRIUMF radiochemistry laboratories are centred around the TR 13 accelerator. Integrated radioisotope production happens in four radiochemistry labs customized for the research and manufacture of radioisotopes and clinical radiopharmaceuticals.

These facilities support three key areas of nuclear medicine research and production: medical isotope production and isolation; innovations in accelerator targets and nuclear chemistry for radiopharmaceuticals; and the application of accelerator beams for life sciences, including bNMR.

Radioisotope Production

With access to the world’s broadest range of cyclotron energies, from 13 to 500 MeV, TRIUMF’s radiochemistry laboratories produce a diverse mix of radioisotopes using gas, liquid and solid targets.

When an experimental radioisotope is identified, TRIUMF beamline and target physicists model the most efficient method for producing it. The TR 13 cyclotron uses gas and liquid targets to produce a variety of radioisotopes, including ¹¹C and ¹⁸F. The produced radioisotopes are transported remotely via a network of valves, feed gasses and liquids that move them out of the target and into a hot cell for chemical processing.

At higher energies, the main 520 MeV cyclotron is used with solid targets to produce a variety of experimental metal medical isotopes, including isotopes of titanium, actinium, bismuth and radium.

Radioisotope Research

For radiochemistry research, TRIUMF’s facilities include a MHESA lab (Meson Hall Extension Service Annex) with four state-of-the-art hot cells, or radiation-shielded, robotic-arm accessed chemistry stations. Each one-meter-cubed hot cell is surrounded on all sides by tons of radiation-shielding lead bricks, with a lead-shielded door with a thick leaded glass window that provides a view of the interior.

Scientists access a hot cell’s interior using a sophisticated robotic arm that enables them to manipulate glassware and other tools for conducting detailed radiochemical experiments and manipulating the manufacturing systems. This includes developing the purification chemistry for potential new radioisotopes.

In the search for new medical isotopes, TRIUMF radiochemistry researchers first work to understand the fundamental physics and chemistry of an isotope. For example, a good radioisotope has a short half-life, and thus leaves little residual radiation in a patient, but must have a long enough half-life to be effectively produced and transported. Thus, TRIUMF scientists work to discover new, rapid radiopharmaceutical synthesis techniques that provide maximum yield, in the shortest time possible.

Similarly, an effective radiopharmaceutical is highly target specific. TRIUMF researchers collaborate with clinical researchers and others to identify targeting molecules, such as sugars, or increasingly, amino acids, peptides and antibodies.

Radiopharmaceutical production with IAMI

For the production of radiopharmaceuticals for clinical and pre-clinical research use in humans, TRIUMF’s IAMI radiochemistry facilities will also operate Health Canada-approved certified Good Manufacturing Practice (cGMP) labs. These cGMP labs are akin to clean rooms and use specialized commercial radiochemistry synthesis systems that include software and hardware compliance and tracking features. This ensures the patient safety of all the TRIUMF-produced medical isotopes, including ¹¹C and ¹⁸F.