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Posts Tagged ‘nuclear medicine’

This is a follow-up from our last post where Paul Schaffer, Head of the Nuclear Medicine Division at TRIUMF, was talking about his experience of being in the media spotlight. In this post, Paul talks more in-depth about the science of medical isotopes.

It all started 19 months ago. A grant that would forever change my perspective of science geared specifically toward innovating a solution for a critical unmet need—in this situation, it was the global isotope crisis. In 2010, not too long out of the private sector, I was already working on an effort funded by NSERC and CIHR through the BC Cancer Agency to establish the feasibility of producing Tc-99m—the world’s most common medical isotope—on a common medical cyclotron. The idea: produce this isotope where it’s needed, on demand, every day, if and when needed. Sounds good, right? The problem is that the world had come to accept what would have seemed impossible just 50 years ago.

The current Tc-99m production cycle, which uses nuclear reactors. Image courtesy of Nordion.

We are currently using a centralized production model for this isotope with just a six hour half-life. This model involves just a handful of dedicated, government-funded research reactors, producing molybdenum-99 from highly enriched uranium (which is another issue for another time). Moly, as we’ve come to affectionately call it, decays via beta emission to technetium, and when packaged into alumina columns, is sterilized, and encased in a hundred pounds of lead. It is then shipped by the thousands to hospitals around the world. The result: the world has come to accept Tc-99m, which is used in 85% of the 20 to 40 million patient scans every year as an isotope available from a small, 100 pound cylinder that was replaced every week or so, without question, without worry. Moly and her daughter were always there…but in 2007 and again in 2009, suddenly they weren’t. The world had come to realize that something must be done.

In the middle of our NSERC/CIHR effort, we were presented with an opportunity to write a proof-of-concept grant based on the proof-of-feasibility we were actively pursuing. Luckily, the team had come far enough to believe we were on the right track. We believed that large scale curie-level production of Tc-99m using existing cyclotron technology was indeed possible. The ensuing effort was—in contrast to the current way of doing things—ridiculous.

With extensive, continuous input from several top scientists from around the country, I stitched together a document 200 pages long. It was a grant that was supposed to redefine how the most important isotope in nuclear medicine was produced. 200 pages, well 199 to be exact, describing a process—THE process—we were hopefully going to be working on for the next 18 months. We waited…success! And we began.

The effort started the same way as the document – with nothing more than a blank piece of paper. Blank in the sense that we knew what we had to do, we just had not defined exactly how we were going to achieve our goal. But what happened next was a truly remarkable thing; with that blank sheet, I witnessed first-hand a team of people imagine a solution, roll up their sleeves and turn those notions into reality.

If you would like to read the PET report, click here




–by Nigel S. Lockyer, Director

Last week I gave a colloquium at the University of Pennsylvania (Penn), my former institution of 22 years. I talked about the on-again off-again worldwide medical isotope crisis and the proposed Canadian solutions. It was not what they really expected, since after all I am a particle physicist and Director of TRIUMF, a particle and nuclear physics laboratory. But that was part of the appeal!

Lots of friends and former colleagues from the department as well as quite a few from the medical school came to hear about the problem and our proposed solutions. Medical isotopes are used in roughly 40 million nuclear medicine procedures around the world and about half of these are in the U.S. The problem is a worldwide shortage of technetium-99m, or Tc-99m, the most popular medical isotope. It is used for heart perfusion imaging (which shows blood flow in the heart muscle, something a doctor wishes to see after a possible heart attack) and to identify bone metastasis. Tc-99m is made primarily in two ageing reactors, the NRU in Canada and the Petten in the Netherlands, both over 50 years old and showing signs of wear. About two years ago they managed to both go offline at the same time for an extended period for needed repairs. The ensuing medical isotope shortage made headlines around the world.

The good news is that my audience seemed to stay awake. Better still, after the lecture, I asked one of the students what they learned and the answer was simply that accelerators were the answer. I was pleased. The message was apparently clear to at least one person…I must say, at least one highly perceptive person. My experience tells me that the best colloquia are the ones where the listeners go home that evening and share the story with their families. The day after the colloquium, one faculty member told me that he had discussed the issues with his kids that evening. Mission accomplished…sort of!

Although there are several solutions to the medical isotope crisis being proposed with accelerators in Canada and now the U.S., and reactors in the U.S. and Europe, I focused in my talk primarily on the approach using small medical cyclotrons, a area of expertise of TRIUMF and Canadian industry (for example, ACSI in Vancouver, which grew out of a collaboration with TRIUMF two decades ago, and manufactures small medical cyclotrons with the prefix “TR”). Another company, BEST, located near Ottawa is also starting to manufacture small medical cyclotrons. In a nutshell, we think that a small cyclotron, a TR-19 for example, running with a few hundred micro-amps of beam current should be capable of supplying enough Tc-99m for a city of roughly 2 million people (think Vancouver). Much work is ongoing at the BC Cancer Agency, Lawson Health Centre in London Ontario, the Centre for Probe Development at McMaster University and TRIUMF. With luck, we will have a positive answer in about 15 months. The world will pay attention (we hope) and certainly our colleagues at Penn are paying attention since they have two small cyclotrons. Enough for Philadelphia? they asked.

Let’s get off topic for a bit. Penn houses the oldest medical school in the United States (1765) and today has over 1700 full time faculty today. That is a huge program. The medical school complex is like a small city itself: throw in Children’s Hospital of Philadelphia (ranked as one of the best in the U.S. by U.S. News and World Report and ranked number one in pediatrics in 2008), the VA Hospital, the Children’s Seashore House Hospital…you get the picture. A new addition just down the street is the Abramson Cancer Center.  I was peripherally involved in the embryo of what is now the new Roberts Proton Therapy Centre. The Roberts Proton Therapy Center is the world largest proton therapy center associated with an academic medical center in the world and one of only six such centers in the United States. (Canada does not have proton therapy except the small ocular melanoma program at TRIUMF.) The Roberts Proton Therapy Center features five treatment rooms:  four gantries with 90-ton rotational machines designed to deliver the therapeutic beam at the precise angle prescribed by the physician, and one fixed-beam room. It is a very impressive facility. I have several friends who work at or are associated with the centre. Oh, did I mention it uses a cyclotron (manufactured by IBA, a Belgium company) to make the beams of protons. I am getting off topic—none of this was in my talk. Back to radiology.

Penn is also well known, to say the least, in radiology; they even maintain a short online history.  Quoting from this  article,

“Radiology at Penn began even before the beginning. In late 1895, German physicist Wilhelm Conrad Roentgen announced his seminal discovery of x-rays. Almost immediately, Penn Physics Professor Arthur Willis Goodspeed realized he had produced x-rays almost six years before, and had the physical plates to prove it. But rather than looking backward, Goodspeed looked forward instead. He quickly teamed with Penn surgeons J. William White and Charles Lester Leonard to produce, on February 4, 1896, one of the first recorded patient exposures using x-rays. That spring, Leonard was named the University Hospital’s first “skiagrapher,” and arguably the first academic department of radiology in the United States and, perhaps, the world was born.”

Roentgen's first x-ray

The original May 18th, 1903 NY Times article can be found online.

“The first x-rays (called “skiagraphs”) were taken of extremities. By June of 1896, the chief of surgery used a skiagraph to locate a toy jack that a child had swallowed. Within months, several hospital departments were using roentgen rays for diagnosis, surgical planning, and follow-up. In 1898 , Charles Lester Leonard used X-rays as a method to identify urinary stones. He also wrote the first paper on the hazards of X-rays.”

That subject is still topical as we all know.

“In 1905 Henry Pancoast described the utility of bismuth and then barium for contrast in radiology studies.” Among many other contributions, he is known for his description of Pancoast’s tumor , a large cancerous tumour in the lung most likely caused by smoking. “He also later described the relationship of prolonged irradiation and the development of leukemia and the use of X-rays in the treatment of Hodgkin’s disease and leukemias. Henry Pancoast was appointed as the first Professor of Radiology (roentgenology) in the United States.”

“More recently, in 1964 David E. Kuhl developed the technique of Single Photon Emission Computed Tomography (SPECT) and the principles of Positron Emission Tomography (PET). In 1976 the world’s first FDG (fluorodeoxyglucose) PET image was obtained at Penn, starting an ongoing new era in functional imaging.” How big is that? The department currently performs more than 1,045,000 procedures annually. You get the picture…a busy place clinically and in research.

In the last several months Penn has been in the press for developing an F-18 labeled molecule that attaches to amyloid plaque, a possible cause (or result) of Alzheimer’s disease. This is not the first such tracer to attach to the plaque. The best known is Pittsburgh Compound B or PIB that is labeled with C-11 which has only a 20 minutes half life (C-11 is an isotope of carbon with one less neutron) . PIB works well, and it has been used at TRIUMF and UBC. However only medical centres with cyclotrons can make PIB and thus its success has set off a rush to make a similar compound labeled with F-18 (not to be confused with CF-18, a Canadian jet fighter), which may be more practical because it can be shipped to a 2-hour radius. Eli Lilly just bought the small start-up company that developed the successful radiotracer. TRIUMF is not yet at the level of developing breakthrough radiotracers like this one. Once they are developed elsewhere, we make them and use them for research or supply them for clinical use to the local research communities.

Penn’s Professor Cam Kuch developed a molecule EF5, which attaches to hypoxic tumours (tumours with reduced oxygen content). These tumours are radiation resistant and often require some treatment other than radiation….for example chemo-therapy. TRIUMF’s Mike Adam developed the chemistry to attach F-18 to this molecule and it is now used in PET imaging at the BC Cancer Agency for some patients to understand more about their cancerous tumour. Thanks Cam. Thanks Mike.

I finished my talk, acknowledged my TRIUMF, UBC and BC Cancer colleagues who teach me about all the great research they are doing here in BC and I realized by the high level of interest at Penn in what we were doing that I had successfully brought coals to Newcastle ….or medical isotopes to Penn.