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.