15 Nov 2019 David Kramer
Two North American companies hope their novel production processes for technetium-99m give them a leg up in an increasingly crowded market.
The global supply chain for the world’s most-used radioisotope, the medical imaging tracer technetium-99m, is notoriously unreliable. When one or more of the handful of reactors producing 99mTc’s parent isotope, molybdenum-99, are off-line for scheduled maintenance or because of unforeseen circumstances, a shortage rapidly develops. For at least 18 months, two facilities, in South Africa and Australia, have been off-line or operating at reduced capacity, and no other producer has been able to take up all of the slack.
As US firms scramble to establish market share in the 99Mo market, a Canadian company now says it is nearly ready to deploy its novel approach to making 99mTc, one that skips 99Mo altogether. ARTMS Products in Vancouver hopes to revolutionize the manufacture and distribution of 99mTc by enabling more than 1100 hospitals and labs equipped with medical cyclotrons to produce the isotope directly at the point of use.
Meanwhile, SHINE Medical Technologies in Wisconsin announced last month that it had set a new world record for the number of neutrons produced in a steady-state fusion reaction, which lasts for seconds or more. SHINE intends to use fusion neutrons to make 99Mo and other radioisotopes from enriched uranium.
A novel technetium technique
Nearly all the world’s 99Mo sources use neutrons supplied from a nuclear reactor to irradiate uranium targets. The produced 99Mo is then chemically separated from other fission products, embedded on an alumina sorbent, and packed for shipment inside containers known as generators. With a half-life of 66 hours, the 99Mo decays to 99mTc, which is eluted with saline solution at radiopharmacies for individual patient doses.
ARTMS is taking a different approach. Its process irradiates solid targets containing 100Mo in a cyclotron. A reaction in which the stable nucleus takes in a single proton and ejects two neutrons yields 99mTc, which has a six-hour half-life.
The solid-target technology has already been used at a half dozen hospitals to produce other medical radioisotopes, such as gallium-68, copper-64, and zirconium-89. Paul Schaffer, ARTMS chief technology officer and an associate director of TRIUMF, Canada’s national accelerator facility, says the company will submit an application within weeks to Canadian regulators for approval of its 99mTc process. Canada’s health department will then have roughly 300 days to decide.
Using the ARTMS process, Schaffer says, a typical 16 MeV cyclotron could produce enough 99mTc to serve an area with a population of 1 million; a 24 MeV machine could serve a population of 4.5 million, producing thousands of patient doses in a single irradiation cycle. A recent survey by the International Atomic Energy Agency identified around 1400 medical cyclotrons worldwide. Schaffer estimates that 80% of them are powerful enough to make 99mTc.
The ARTMS equipment can be retrofitted to most medical cyclotrons for just a few thousand dollars, says Schaffer, and in addition to 99mTc, it can also produce isotopes that are useful for positron emission tomography (PET) imaging. The company says it has demonstrated record 68Ga production from zinc-68 targets. The gallium isotope is used in PET scans to detect and image neuroendocrine and prostate tumors.
Conventional 68Ga generation involves the decay of germanium-68. But 68Ge has a half-life of 271 days, and according to ARTMS, there is a 12- to 18-month backlog for the generators from which 68Ga is eluted from the sorbent. The generators cost $85 000 and produce just enough 68Ga for one or two scans per day, says Schaffer. By comparison, ARTMS’s solid cyclotron targets can provide 10 patient doses of 68Ga every 90 minutes, he says.
Adjusting to the ARTMS technology could be a challenge for the operators of cyclotrons at medical centers. Medical isotope production typically involves the irradiation of standardized, decades-old aqueous or gaseous targets. But the ARTMS 100Mo targets are solid. Schaffer acknowledges that for his technology to gain traction, cyclotron users would have to become more comfortable with nonstandard targets.
Greg Piefer, founder and CEO of competitor SHINE, says ARTMS’s solid-target technology is likely to make 99mTc far more expensive than the going rate of $20 per dose. Schaffer disputes that. “We’ve done the math and are confident that the cost of producing 99mTc by cyclotron is very similar to 99mTc obtained from 99Mo,” he says. Schaffer acknowledges, however, that the dose price will depend on how far the product has to travel from its source, given its very short half-life.
SHINE plays the long game
SHINE’s process is unique in using neutrons from fusion reactions to produce 99Mo. Piefer says his long-term goal is to produce energy via nuclear fusion; medical isotopes, neutron imaging, and transmuting nuclear waste are stepping-stones toward that objective. He plans to begin producing 99Mo in 2021. “We are building economic engines that can largely fund the path through private means without having to suck government or investor wallets dry,” he says.
SHINE and partner company Phoenix LLC announced last month that their accelerator-driven neutron generator yielded 4.6 × 1013 fusion neutrons per second, a rate they claim eclipses by nearly 25% the previous record for steady-state fusion, held by a long-shuttered facility at Lawrence Livermore National Laboratory.
The high-energy neutrons were produced by deuterium–tritium fusion reactions and lasted for about 15 minutes, until the small amount of tritium held at the company’s test site ran out, says Piefer. For 99Mo production, SHINE will accelerate deuterons to strike a target containing 90% tritium. The 14 MeV neutrons from fusion will be slowed to thermal energies before they hit fission targets containing uranium enriched in the 235U isotope to 19.5%. That’s a hair below the threshold 20% content that defines weapons-grade highly enriched uranium (HEU). No commercial supplier of that high-assay low-enriched material presently exists, so SHINE plans to obtain it from diluted HEU stockpiled at the Department of Energy’s Y-12 plant in Oak Ridge, Tennessee. Ontario Power Generation will supply tritium from the utility’s heavy-water purification plant in Darlington, Ontario.
Evan Sengbusch, Phoenix’s president, says the fusion neutron generators are also useful in nondestructive testing and neutron imaging, applications that currently require reactors. Phoenix has development contracts with the US Army and Navy for other neutron-generator applications.
Two other US companies plan to use accelerators in producing 99Mo. In October, NorthStar Medical Radioisotopes broke ground on a facility in Beloit, Wisconsin, that will eventually house eight electron accelerators dedicated to medical isotope production. NorthStar’s process will involve knocking a neutron from 100Mo. A company spokesperson says 99Mo production is expected to begin in late 2022.
Niowave in Lansing, Michigan, has plans to produce 99Mo from a superconducting linac of its own design using low-enriched uranium targets. It expects to commence operations in 2023. Niowave, NorthStar, and SHINE are among more than a half dozen US firms that have received tens of millions of dollars in 50–50 cost-shared funding from the Department of Energy’s National Nuclear Security Administration. The agency was instructed in 2012 legislation to encourage new domestic sources of 99Mo that don’t use HEU.
NorthStar became the first US 99Mo supplier in three decades last year when it started up a non-accelerator process involving the capture of neutrons by 98Mo targets. The University of Missouri Research Reactor supplies the neutrons. The company is awaiting US Food and Drug Administration approval to add two processing lines to its existing one.
Link to the article –https://physicstoday.scitation.org/do/10.1063/PT.6.2.20191115b/full/