Sunday, March 24

PET Project

Phelps' scanner can detect diseases and measure brain activity

It can detect early signs of Alzheimer’s Disease,
Parkinson’s Disease, heart disease and cancer, or even show
doctors what areas of your brain are stimulated while you’re
listening to music or moving your arms.

It is a machine called the Positron Emission Tomography scanner,
first invented in 1973 by Professor Michael Phelps, now the Chair
of the UCLA Department of Molecular & Medical Pharmacology.

Searching for new ways to detect health problems early on,
medical researchers have always struggled to find the difference
between healthy cells and diseased ones.

“When I first started teaching students in the medical
school, we talked about medicine and biology, but (the students)
couldn’t see it. I decided to build a way for them to see
it,” said Phelps.

Phelps realized in the early 1970s that if he could
“˜tag’ a common chemical or drug as it entered a
patient’s body, then he could discover exactly where and when
the body was using it abnormally.

Before the PET scanner, one of the most common ways to measure
the chemical reactions in the body was by a tissue sample, which
only tests one small part of the body or by autopsy after the
patient’s death.

“When I built the first (PET scanner) I was excited …
the inventor has strong beliefs, but it can be hard to convince
others,” said Phelps.

Though some were slow to accept it at first, Phelp’s PET
scanner eventually emerged as a revolutionary combination of
nuclear physics, chemistry, mathematics and biomedical imaging.

The first step is the creation of a radioactive
“˜tag’ which is an unstable isotope that emits a very
small and harmless amount of radiation.

This isotope tag is then chemically bonded to whichever
substance the researcher wants to measure in the body, whether it
be oxygen, glucose, dopamine or even a particular medicine or drug.
Finally, the doctors introduce the tagged chemical into the

As the tagged substance circulates around the bloodstream, the
radioactive isotope emits a small amount of radiation that the PET
scanner can detect. The isotope gives away the location to which
the chemical is attached, allowing researchers to measure exactly
where and in what concentrations the body is using it.

This technology has allowed an explosion of knowledge about once
mysterious conditions. Tagging a glucose-like chemical called FDG
can reveal cancerous tumors in their early stages, since they use
sugar differently than healthy cells.

Now, doctors can finally see it.

The accuracy of PET in detecting cancer is eight to 43 percent
greater than other scanning equipment, and this knowledge can
change the way 15 to 50 percent of cancer patients are treated,
Phelps said.

A clinical PET scan costs insurance companies approximately
$1400, compared to about $600-$800 for a CT scan, which is more
similar to an X-ray. Phelps noted that though the cost seems high,
the cost of a misdiagnosis caused by a less accurate scan can be
far greater, especially for cancer patients.

PET has also become hugely important in one of the newest fields
of medicine ““ gene therapy ““ because there is almost no
other effective way to determine whether it is successful.

In gene therapy, doctors inject a therapeutic gene into a
harmless virus, called a vector, and then introduce it to a
patient. The virus spreads the new gene throughout the body,
changing the DNA of the living patient. But the only way the
researchers can actually measure whether the new gene is being
expressed correctly is by using PET technology to tag it in the
first place.

In 1996, UCLA researchers Simon Cherry, Satya Murthy, Jorge
Barrio, Sanjiv Gambhir and Mike Phelps developed Micro-PET, a
version of the scanner for gene-therapy experiments on mice that
represents a big step toward human use.

“We could go into a living subject and watch the
expression of genes. We can actually watch whether a vector goes
into a target location (in the body),” said Phelps.

Harvey Herschman, a colleague of Phelps’ at the Crump
Institute for Molecular Imaging, hinges the success of gene therapy
on the potential of Phelps’ PET.

“Mike is a very visionary person, very creative, very
imaginative. The (overall) question of gene therapy is still up in
the air, but if it is successful, it will be because of PET
scanning,” said Herschman.

Of all these accomplishments, Phelps said that the most striking
experience he had with PET involved research in the early 1980s on
the brains of small children. By measuring levels of glucose used
in the brain, he determined the metabolism, or activity, taking
place in the minds of infants.

Though at birth only a few basic structures were active in the
infants’ brains, by about one and a half years old the brain
looked more or less mature.

But between two years and 10 years old, the brain was at twice
the adult value of activity before declining again between ages ten
and twenty to a normal adult level, said Phelps. At first, the
researchers could not understand why the brain was so highly active
during those years.

Analyzing this knowledge eventually led Phelps and other
researchers to conclude the now-accepted theory that small children
have huge potential in learning from two until 10 years old, when
the brain is most adaptable to new skills and information.

“This taught us something ““ that the brain could
adapt and compensate for damage,” Phelps said.

Phelps used this conclusion to justify removing the entire
left-hemisphere of a severely epileptic child who previously had to
be continuously sedated. After extensive physical therapy, the
child’s brain adapted and he recovered from both the surgery
and the epilepsy, Phelps said.

Among numerous other awards and honors, Phelps received the
prestigious Enrico Fermi award in 1998 for his invention of the PET
scanner and advancement of its use to treat neurological disorders,
heart disease, and cancer.

Today, Phelps continues to conduct research and teaches graduate
seminars at UCLA in molecular biology.

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