Friday, March 23, 2018

95gTc and 96gTc as Alternatives to Medical Radioisotope 99mTc

Intermediate Physics for Medicine and Biology: 95gTc and 96gTc as Alternatives to Medical Radioisotope 99mTc In Chapter 17 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the most widely used radioisotope in nuclear medicine: 99mTc (technetium-99m). Previously in this blog (here, here, and here) I described the looming shortage of 99mTc. In a recent paper in the open access journal Heliyon (Volume 4, Article Number e00497, 2018), Hayakawa et al. review “95gTc and 96gTc as alternatives to medical radioisotope 99mTc.” I don’t know enough nuclear medicine to judge if 95gTc and 96gTc are realistic alternatives to 99mTc, but the idea is intriguing. Below I reproduce an abridged and annotated version of the introduction to this interesting paper (my comments are in italics and enclosed in brackets []). Enjoy!
“Various radioisotopes, such as 99mTc (half-life 6.02 h [hours]), 201Tl [thallium-201] (half-life 3.04 d [days]), and 133Xe [xenon-133] (half-life 5.27 d), are used for single-photon emission computed tomography (SPECT) in medical diagnostic scans. In particular, 99mTc has become the most important medical radioisotope at present… Over 30 commonly used radiopharmaceuticals are based on 99mTc [for example, 99mTc–sestamibi, 99mTc–tetrofosmin, and 99mTc-exametazime]... The 99mTc radioisotopes are supplied by 99Mo/99mTc generators, which continuously generate 99mTc through the β-decay of the parent nucleus 99Mo [molybdenum-99 is trapped in alumina (Al2O3) where it decays to pertechnetate (TcO4-); eluting solution flowing through the alumina collects the 99mTc]... This supply method provides two excellent advantages. First, it is possible to transport 99Mo/99mTc generators from a production facility to any place in the world because the half-life of 99Mo is... 2.75 d. Second, when a 99Mo/99mTc generator is transported to a hospital, 99mTc can be produced fresh for up to 2 weeks by daily milking/elution from this 99Mo/99mTc generator. At present, the parent nucleus 99Mo is produced in nuclear reactors by the neutron-induced fission of 235U [uranium-235] in highly enriched uranium (HEU) targets, in which the fraction of 235U is approximately 90%. However, some nuclear reactors that have supplied 99Mo require major repairs or shutdown [for example, the Chalk River reactor in Ontario, Canada], which may lead to a 99mTc shortage. Thus, many alternative methods to produce 99Mo or 99mTc [such as in a cyclotron] without HEU have been proposed…
The September 11th terrorist attacks in Washington D.C. [these attacks actually took place in New York City, at the Pentagon in Arlington County Virginia, and near Shanksville, Pennsylvania] in 2001 also affected medical radioisotope production from the viewpoint of the safeguards of nuclear materials. The control of fissionable nuclides such as 235U and 239Pu [plutonium-239] is important for the safeguards of nuclear materials… The International Atomic Energy Agency (IAEA) hopes to discontinue 99mTc production using HEU targets, which can be transmuted into nuclear weapons... In the near future, 99mTc will be supplied by nuclear reactors using LEU [low-enriched uranium] targets in addition to HEU. The Nuclear Energy Agency (NEA) reported the prediction that the 99Mo/99mTc supply will be larger than the world demand when the scheduled nuclear reactors using LEU start 99Mo production…

Because the Tc [technitium] chemistry is the same, all the radiopharmaceuticals based on 99mTc can, in principle, be applied to other Tc isotopes. There are five Tc isotopes with half-lives in the range from hours to days: 94mTc (half-life 52 m [minutes]), 94gTc (half-life 4.88 h), 95mTc (half-life 60 d), 95gTc (half-life 20 h), and 96gTc (half-life 4.28 d) [superscript "g" stands for ground state, whereas superscript "m" stands for metastable excited state]… The half-life of 96gTc (4.28 d) is long enough for worldwide delivery from a production facility and lengthy use of up to 2 weeks in hospitals. 95gTc (20 h) can also be transported to a wide area and used for 3–5 days in hospitals. Thus, 95gTc and 96gTc are candidates for alternative γ-ray emitters. However, the decay rates of 95gTc and 96gTc are lower than that of 99mTc by a factor of 3.3 and 17, respectively, because the decay rate of a radioisotope is inversely proportional to its half-life. This fact leads to the question of whether these isotopes can work as 99mTc medical radioisotopes.

In the current study, we present the relative γ-ray flux of these isotopes with simple assumptions. We also estimate the patient radiation does [dose] per Tc-labeled tracer using… PHITS [Particle and Heavy Ion Transport code System, a general purpose Monte Carlo particle transport simulation code]... Various nuclear reactions that are production methods of Tc isotopes, such as (p, n) reactions [in which a proton enters the nucleus and a neutron leaves it]…, deuteron [hydrogen-2]-induced reactions…, and 96Ru [ruthenium-96] (n, p)96gTc reactions…, were studied. We consider the production by the (p, n) reaction on an enriched Mo isotope. We also calculate the production rate using a typical PET [positron emission tomography] medical cyclotron [If you must make 96gTc in a cyclotron, why not make 99mTc in the cyclotron instead?]. Because the energies of decay γ-rays of these Tc isotopes are typically higher than 200 keV, they are not suitable for the traditional SPECT cameras. Thus, we also discuss the property of possible ETCC [Electron-Tracking Compton Camera] for high energy γ-rays.”

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