Intermediate Physics for Medicine and Biology: Odds and Ends

It’s time to catch up on topics discussed previously in this blog.

The Technetium-99m Shortage

Several times I have written about the Technetium-99m shortage facing the United States (see here, here, here, and here). Russ Hobbie and I discuss ^99mTc in Chapter 17 of the 4th edition of Intermediate Physics for Medicine and Biology.

The most widely used isotope is ^99mTc. As its name suggests, it does not occur naturally on earth, since it has no stable isotopes. We consider it in some detail to show how an isotope is actually used. Its decay scheme has been discussed above. There is a nearly monoenergetic 140-keV γ ray. Only about 10% of the energy is in the form of nonpenetrating radiation. The isotope is produced in the hospital from the decay of its parent, ⁹⁹Mo, which is a fission product of ²³⁵U and can be separated from about 75 other fission products. The ⁹⁹Mo decays to ^99mTc.

An interesting article by Matthew Wald about the supply of ^99mTc appeared in the February 6 issue of the New York Times. Wald writes

For years, scientists and policy makers have been trying to address two improbably linked problems that hinge on a single radioactive isotope: how to reduce the risk of nuclear weapons proliferation, and how to assure supplies of a material used in thousands of heart, kidney and breast procedures a year. . .

The isotope is technetium 99m, or tech 99 for short. It is useful in diagnostic tests because it throws off an easy-to-detect gamma ray; also, because it breaks down very quickly, it gives only a small dose of radiation to the patient.

But the recipe for tech 99 requires another isotope, molybdenum 99, that is now made in nuclear reactors using weapon-grade uranium. In May 2009, a Canadian reactor that makes most of the North American supply of moly 99 was shut because of a safety problem. A second reactor, in the Netherlands, was simultaneously closed for repairs.

The 54-year-old Canadian reactor, Chalk River in Ontario, is running now, but its license expires in four years. Canada built two replacement reactors, but even though they turned out to be unusable, their construction discouraged potential competitors ...

One solution to the ^99mTc shortage may be to produce ⁹⁹Mo in a cyclotron. The New York Times article discussed this solution briefly, and more detail is supplied by a report written by Hamish Johnston and published on the website medicalphysicsweb.org (all readers of Intermediate Physics for Medicine and Biology should become familiar with medicalphysicsweb.org). The gist of the method is to bombard ¹⁰⁰Mo with protons in a cyclotron. Recently, researchers have made progress in developing this method. Johnston writes

Scientists in Canada are the first to make commercial quantities of the medical isotope technetium-99m using medical cyclotrons. The material is currently made in just a few ageing nuclear reactors worldwide, and recent reactor shutdowns have highlighted the current risk to the global supply of this important isotope.

See also an article in the Canadian newspaper, The Globe and Mail.

The Linear-No-Threshold Model

Another topic addressed recently in this blog is the risk of low levels of radiation, discussed in Chapter 16 of Intermediate Physics for Medicine and Biology.

In dealing with radiation to the population at large, or to populations of radiation workers, the policy of the various regulatory agencies has been to adopt the linear-nonthreshold (LNT) model to extrapolate from what is known about the excess risk of cancer at moderately high doses and high dose rates, to low doses, including those below natural background.

On February 21, medicalphysicsweb.org published an article asking “Does LNT model overestimate cancer risk?” Science writer Jude Dineley reports

An in vitro study has demonstrated that DNA repair mechanisms respond more effectively when exposed to low doses of ionizing radiation, compared to high doses. The observations potentially contradict the benchmark for radiation-induced cancer risk estimation, the linear-no-threshold (LNT) model, and if so, could have large implications for cancer risk estimation (PNAS 109 443).

The Proceedings of the National Academy of Sciences paper that Dineley cites is titled “Evidence for Formation of DNA Repair Centers and Dose-Response Nonlinearity in Human Cells,” and is written by a team of researchers at the Lawrence Berkeley National Laboratory. The abstract is given below.

The concept of DNA 'repair centers' and the meaning of radiation-induced foci (RIF) in human cells have remained controversial. RIFs are characterized by the local recruitment of DNA damage sensing proteins such as p53 binding protein (53BP1). Here, we provide strong evidence for the existence of repair centers. We used live imaging and mathematical fitting of RIF kinetics to show that RIF induction rate increases with increasing radiation dose, whereas the rate at which RIFs disappear decreases. We show that multiple DNA double-strand breaks (DSBs) 1 to 2 μm apart can rapidly cluster into repair centers. Correcting mathematically for the dose dependence of induction/resolution rates, we observe an absolute RIF yield that is surprisingly much smaller at higher doses: 15 RIF/Gy after 2 Gy exposure compared to approximately 64 RIF/Gy after 0.1 Gy. Cumulative RIF counts from time lapse of 53BP1-GFP in human breast cells confirmed these results. The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation. However, our discovery of DSB clustering over such large distances casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation.

PNAS published an editorial by Lynn Hlatky, titled “Double-Strand Break Motions Shift Radiation Risk Notions,” accompanying the article. Also, see the Lawrence Berkeley lab press release.

See Russ Hobbie Demonstrate MacDose

Finally, my coauthor Russ Hobbie is now on iTunes! His video “Photon Interactions: A Simulation Study with MacDose” can be downloaded free from iTunes, and provides much insight into how radiation interacts with tissue. The description on iTunes states

This 26-minute video uses a computer simulation to demonstrate how x-ray photons interact in the body through coherent scattering, the photoelectric effect, Compton scattering, and pair production. It emphasizes the statistical nature of photon attenuation and energy absorption. The viewer should be able to distinguish between the quantities energy transferred, energy absorbed, Kerma, and absorbed dose, describe the effect of secondary photons on energy transferred and absorbed dose, and understand the effect of photons of different energy when used for radiation therapy.

You can also find Russ’s video on Youtube, included below.