Some new developments in radiation diagnosis and treatment

Normal bone marrow

There’s nothing like a good fright to spark people into action. Tell someone that they need to have a triple bypass and they’re likely to finally get around to exercise and healthy eating; diagnose a person with lung cancer and they might finally stop smoking. A good enough scare can get people to stop drinking, get them into church, can get them to install home alarm systems, and so much more – whatever is needed to help protect against whatever caused the scare. The last several years the threat of nuclear and radiological terrorism has given us all a good scare and one of our responses has been to throw a lot of money into improving our ability to respond medically to such an attack. A lot of strategies have been pursued – I’d like to talk about two of them (one for diagnosis and the other for treatment) that struck me as being particularly noteworthy.

Diagnosis

When it comes to radiation health effects everything comes down to dose – a person with 100 rem (1 Sv) will likely develop radiation sickness, 400 rem (4 Sv) has a 50% chance of being fatal without medical treatment, and 900 rem (9 Sv) will almost certainly be fatal with even the best medical attention. Knowing a person’s radiation dose not only helps physicians to choose the proper course of treatment but it also helps them to understand how much weight to give radiation effects when assessing a patient’s overall condition – a patient who has received only 25 rem (0.25 Sv) for example isn’t likely to experience significant health effects and the physicians can concentrate on non-radiological concerns (broken bones, lacerations, and so forth). One way to do this is to carefully examine the cell’s chromosomes for specific types of damage that are correlated with radiation exposure The problem is that determining a person’s radiation exposure – called biodosimetry – is time-consuming and complex and, in the event of a large-scale population exposure, getting accurate biodosimetry for a large number of people can take weeks. This is far too long to be useful.

In the last few years a Columbia University team led by David Brenner has developed an automated system that addresses many of these problems – the Rapid Automated Biodosimetry Tool(abbreviated RABiT).

The RABiT system is able to perform biodosimetry on as many as 30,000 samples daily – a huge advance over current techniques. Without going into the details let it suffice to say that the RABiT system adds an amazing level of capability to our national radiation biodosimetry capacity – Brenner and his colleague Guy Garty (others have contributed as well, but Brenner and Garty are the major forces behind this work) are to be commended for a genuinely innovative approach to solving a huge problem.

The biggest problem with using the RABiT system is the sheer logistics – in order to be effective there has to be a way to collect and process tens of thousands of samples daily, and this in a city that will be trying to grapple with the aftermath of a radiological or nuclear emergency. Not only that, but there is little room for error in sample identification – every single sample must be able to be unambiguously linked to the person from whom it was collected to make sure that everyone receives the appropriate medical care. And even more fundamentally, there have to be facilities to collect these samples and the population has to know where these facilities are (and to be able to reach them). These problems are not insoluble, but they are very real and, until they are solved, the RABiT system cannot be effectively implemented.

Yet another factor is that any large city that has been attacked will need to have more than one RABiT device available – even a network of 10 of these devices running around the clock will take 2-3 days to run a million samples. But it doesn’t make sense to have a number of expensive machines sitting around gathering dust while waiting for a radiological or nuclear emergency – this would be a waste of money and a waste of resources, in addition to the fact that we would have no way to know whether or not the machines (and the staff needed to operate them) would work when they’re needed. For this reason it makes sense to develop other routine uses that would justify maintaining a number of these devices in continual operation – then, in the event the worst happens, they could be converted from routine to emergency operation, rather than starting them up from scratch. For this reason Brenner and Garty are teaming up with a number of other universities and governmental agencies to look for routine uses that would support this unique capability (if you’re interested, the grant proposal deadline is still two months away).

Treatment

Knowing how much radiation dose someone received is one thing; doing something about it is another. There was another fascinating development that was published by Dana-Farber physician Eva Guinan and a number of colleagues just a few months ago (November 23, 2011) in the journal Science and it deals with treating people for high levels of radiation exposure. For the first time there seems to be promise of a treatment that could help to keep people alive who might otherwise die of high radiation exposure – if this pans out it could be hugely important.

Some of our tissues and organs are more sensitive to the effects of radiation than others. Oxygen tends to enhance the amount of damage a given amount of radiation will cause so cells that are well-oxygenated tend to be more radiation-sensitive than are the less-oxygenated cells. Cells that reproduce rapidly are also more radiation-sensitive, as are less specialized cells. Putting all of this together helps to explain why, for instance, our neurons are relatively radiation-resistant (they are highly specialized cells that divide only rarely) and why the cells that line our digestive tract and our blood-forming organs are among the first affected by radiation. In fact, a drop in blood cell counts is one of the earliest signs of excessive radiation exposure and this drop can become life-endangering at higher radiation doses.

Relatively low doses of radiation (up to about 100 rem or 1 Sv) will cause blood cell counts to drop but it doesn’t become life-endangering until the dose gets to about 400 rem (4 Sv) – at this level of exposure (without medical care) about half of those exposed will die. With medical treatment, much of which is aimed at supporting a patient whose immune system and blood-forming organs have been severely compromised, the 50% lethal dose increases to about 800 rem (8 Sv). A major cause of death is infection due to the destruction of an organism’s immune system.

Mice (the organism Guinan’s group tested, since it’s not quite ethical to expose humans to near-lethal radiation doses in experiments, no matter how well-intended) a radiation dose of 700 rem (7 Sv) is nearly always fatal, killing between 95-100% of the mice exposed. By treating mice with two drugs – one that helps replace some proteins that are crucial in helping fight off infection and a powerful antibiotic. Not only that, but the bone marrow of exposed mice recovered much more quickly after treatment. With these drugs, between 70-80% of the exposed mice survived, a phenomenal turnabout.

Both of the drugs Guinan tested are already used in people, albeit for different purposes, and both have been shown to be safe. This means that, even if the patient’s dose is not precisely known, there is little down side to treatment. Another plus is that the adverse health effects of radiation take some time to appear – this treatment is effective even if it takes place a day after the exposure. The bottom line is that, if tested and approved for human use, this treatment promises to be able to save lives. But, of course, it does need to be tested to ensure that it lives up to its promise.

Summary

We may never have a large-scale radiological or nuclear emergency that would call for these developments. Consider – until Chernobyl there was no need for large-scale biodosimetry and after Chernobyl there was no further need for over two decades with the Fukushima accident. And even Chernobyl had only a relative handful of people who would have benefitted from Guinan’s work. But both of these developments offer the potential for utility in more routine circumstances – that being the case it seems to make sense to invest today to develop this new technology and drug therapy so that we will have them available should we ever need them in an emergency, and so that we can use them more routinely even in the absence of another major disaster.

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Dr Y is a certified health physicist, trained in nuclear power plant design and operations, with experience in nuclear power, environmental science, and planning for radiological and nuclear emergencies. He has 30 years of experience in the areas of nuclear and radiation safety.

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2 Responses to “Some new developments in radiation diagnosis and treatment”

  1. merkwuerdigliebe January 26, 2012 at 1:07 PM #

    Mass screening for radiation effects seems an interesting capability indeed, even if may be just to find legions of worried well.

    However, when it comes to having those devices spread all over the country, I would like to emphasize that the developers should really find the killer app some other discipline has been waiting for for decades. Otherwise, there would just be another expensive apparatus in the hospital, generating unnecessary examinations for its amortization.

    In this case, it is probably cheaper to have a limited number of devices container-mounted in a few centralized civil protection depots and ship or helicopter them to a convenient place when- and wherever needed. Such a scheme may also be more robust: After all, when postulating a significant radiological emergency in the middle of a city, what’s the place where you want to avoid having to work? The hospital in the middle of the city!

  2. jan F Baumgardner, MD, FAAFP February 6, 2012 at 10:01 PM #

    good thinking! Now How do us older guys wih lots of experience in dose/rx (worked in nuclear facility for years) get up to date and availab le and rfeachable in an urgent situation.

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