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Heart Institute makes own medical isotopes: A new face of nuclear medicine

THE OTTAWA CITIZEN: TOM SPEARS, - JULY 4, 2009

http://www.canada.com/Health/face+nuclear+medicine/1760171/story.html

Chief physicist Robert de Kemp holds an empty vial of a Flourine-18 solution which is used during a PET scan.

Photo: Wayne Cuddington, The Ottawa Citizen

Six thousand people each year pass through the glass doors off Ruskin Avenue, walk past the turkey burgers and beef stroganoff at Tickers cafeteria, and go upstairs to have radioactive dye injected into their arms.

At the University of Ottawa Heart Institute, they will wait as the dye -- actually a colourless liquid -- circulates and reaches their hearts.

There, in the muscles of the heart, it will give off radiation in patterns that tell a doctor whether the heart is able to pump properly. It's a picture, painted in gamma rays shooting out from the heart cells.

Rob de Kemp points at one dull area in an otherwise bright image. He's the chief physicist in the department making these images.

"This one might be a little bit of disease. You see there's a lower intensity (of colour) there at the top? So there's been a little less rubidium trapped in the heart muscle."

Rubidium is a radioactive "dye." If it's not reaching some of the heart muscle, then blood isn't, either. Starved for oxygen and nutrients, that muscle can't pump well.

"That's what they're looking for in the scans -- regions where there's less blood flow," de Kemp explains.

The shutdown of the aging NRU reactor at Chalk River has cut off the supply of the main radioactive material the Heart Institute uses, called technetium-99.

But as one supply is squeezed, other materials, including this rubidium dye, can sometimes take its place.

In the institute's basement, there's a machine with a name like a carnival ride -- the cyclotron -- that produces medical isotopes (radioactive atoms) without a nuclear reactor.

To anyone who has toured a nuclear reactor building, the contrast is startling. Reactors are huge machines in earthquake-proof buildings running 24 hours a day, surrounded by layer upon layer of security and shutdown systems, and with radioactive waste that will last for millennia.

They cost hundreds of millions of dollars to build (even the smallest ones), and the last pair built in Canada flunked their safety tests last year and therefore have never operated.

The cyclotron at the Heart Institute is a big metal box in a room that measures about eight by 10 metres. You can walk right up to it safely while it's running.

At night, the staff just turn it off and go home.

This is a new face of nuclear medicine, making medical isotopes that will make pictures of the heart, brain, bones and so on.

De Kemp continues his explanation of the glowing blobs on a computer screen that tell him what a man's heart looks like. He's the institute's chief medical physicist.

"What we can do with a nuclear medicine test is give someone a radioactive dye. The isotope is the radioactive part of the dye," he explains. "So we give a dye that goes to the heart muscle, and shows us how much blood flow there is to the heart muscle."

De Kemp returns to his rotating, three-dimensional computer image shaped like a heart, lit up in artificial yellow and red colours, with one section missing.

The patient may feel fine when he rests. But when he climbs stairs, his heart is trying to pump more blood using only some of its muscles. One side of the heart chamber is squeezing; the other side isn't doing anything. The man's chest hurts, and he runs short of breath easily.

"The isotopes emit radiation. They emit, in this case, gamma rays, which the camera can detect. Some cameras get a three-dimensional view of the heart showing where there is normal blood flow and where there is reduced blood flow due to a blockage or a narrowing in the coronary arteries," de Kemp says.

This test is far easier than the alternative -- sticking a catheter in through a thigh artery, sliding it up to the heart, and releasing material that can produce X-rays of the heart.

The catheter requires a day in hospital, and has the risk of causing bleeding. It's not much fun for the patient. It's slow and therefore more expensive for the hospital to do.

Some people will still get a catheter, but many can avoid it by having the nuclear test alone.

The "dye" itself is a liquid -- radioactive material dissolved in saline (salt water). The dye is injected through a needle, and after a few minutes of travel through the body it arrives at the heart.

But something has to tell the dye where to stop.

Each dye has two parts. One is the radioactive isotope. The other is a chemical, often a drug, that travels to a particular type of cell in the body.

The heart dye's chemical is one that is quickly absorbed by muscle cells, especially when they're working. For a person lying down in a hospital, the hardest-working muscle cells are the heart muscles, pumping away non-stop while the arms and legs are relaxed.

Dyes for making pictures of other parts of the body use chemicals more likely to be absorbed by brain cells, bone cells, the liver, and so on.

Still, the past year's crises involving shutdowns of the venerable NRU reactor at Chalk River illustrate the fragile supply of medical isotopes.

About 80 per cent of what the Heart Institute uses, traditionally, is technetium-99, made from radioactive material from Chalk River. That supply is shut down for now, though there are reduced amounts available from other parts of the world.

Hospitals like technetium. Its long medical history means it is well understood. There is a long list of drugs that hospitals can attach it to -- one drug to carry it to the liver, another for the heart, and so on. It gives off a level of energy that's easy for the camera to "see." It doesn't last long in a patient's body after the test is done.

There's a great deal of current research into better ways to produce technetium, says Dr. Terrence Ruddy, chief of cardiology at the institute.

"On the other hand, say it doesn't work out (because of shortages), there's a lot of work going into alternatives," such as iodine, which comes from a cyclotron.

Rubidium is a major alternative to technetium, and it needs no nuclear reactor. The Heart Institute buys radioactive strontium from a cyclotron in Vancouver, and converts it to rubidium. The "generator" that does this is a bedside box the size of a photocopier.

Indium is used fairly rarely, mostly to make images of infected or inflamed areas. For thyroid images, and some other parts of the body, there's radioactive iodine. And the Heart Institute now uses a lot of thalium for heart images.

And as well as the isotopes -- which are radioactive atoms -- comes a radioactive molecule made at the Heart Institute called sodium fluoride. That's sodium bonded with a radioactive fluorine atom.

"The sodium fluoride test is also one that we will probably make available to patients soon, either here or at The Ottawa Hospital, which also has a PET scanner," de Kemp says. It's used for bone scans to detect suspected cancer.

The cyclotron is what allows the Heart Institute to manufacture radioactive materials without depending on a nuclear reactor at Chalk River (or anywhere else).

The cyclotron's value lies in making radioactive dyes that complement -- even though they can't entirely replace -- radioactive technetium, says Jean DaSilva, the head of radiochemistry for the cardiac PET centre.

Here's how it works: the cyclotron is a machine that accelerates protons -- little particles found in the centre of atoms -- to very high speeds, and shoots them at a target of ordinary atoms such as oxygen, carbon and nitrogen. These speeding protons join themselves to their target atoms.

But the resulting bulked-up atoms are unstable. The extra protons will soon break off and shoot away again. That's what radiation is.

They can make four types of radioactive isotopes in Ottawa, of which fluorine is the most useful for medical images.

But radioactive fluorine decays quickly; it is useful for only a few hours. This means it can't be made in Vancouver and shipped here.

"But since we now have it (the cyclotron) on-site, capacity is not a problem," DaSilva says.

As well, the Heart Institute's machine added a second "beam," or firing line of protons that produce radioactive material, last year, thanks to a grant from the Canada Foundation for Innovation. That increases production, like adding a second assembly line at a car factory.

And if Ottawa heart patients didn't have these radioactive dyes?

"The alternative would be more invasive tests -- more of these procedures where we put catheters up into your leg and injected X-ray dye," de Kemp says.

"Puncturing an artery is not a minor surgery. The costs of that are also much, much higher than nuclear medicine where they might be here for an hour -- in and out, and they have their diagnosis."

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