Biomedical Imaging to be Extended by New Biomedical Isotope Facility
August 16, 1996
By Lynn Yarris, LCYarris@LBL.gov
Beginning in the 1930s, when John Lawrence (brother of Lab-founder
Ernest) and his associates discovered that certain radioactive isotopes
could be safely used in biomedical research, Berkeley Lab has evolved
into a world leader in the field of biomedical imaging. Much of this
research depends upon the use of special radioisotopes that disappear
quickly from the human body.
What makes a biomedical radioisotope safe is its short half-life -- the
time it takes for half of a given amount of the material to decay into
a non-radioactive product. A short half-life means that the
radioisotope can be sent through an organ or tissue and "traced" or
detected to yield an image with no side effects.
"Radiotracers follow along, they don't play," explains Henry
VanBrocklin, a Life Sciences Division chemist with the Center for
Functional Imaging (CFI). VanBrocklin heads the Biomedical Isotope
Facility and oversaw its construction. "The idea of a radiotracer is
to image the physiology without perturbing it."
The short half-lives that make biomedical isotopes safe for humans also
require these isotopes to be used soon after they are produced, or else
they are gone. One common production technique, which Berkeley Lab
researchers helped develop, is the "generator method," in which
long-lived "parent" isotopes continually decay into short-lived
"daughter" isotopes that can be extracted as needed. However, there
are important radioisotopes that can only be produced in cyclotrons or
reactors.
During the 1980s, Berkeley Lab researchers obtained these special
radioisotopes from the 88-Inch Cyclotron. However, since this machine
was built for nuclear physics research, procuring time to produce
biomedical isotopes was difficult and costly. More recently, such
isotopes have been obtained from nearby sites off the Hill, such as UC
Davis and its Crocker Cyclotron. The short half-lives of the isotopes,
however, make their transportation over any distance a problem.
Even 10 years ago, CFI's head, Thomas Budinger, saw the advantage in
producing radioisotopes at Berkeley Lab in a dedicated facility. He
initiated the process that led to construction of the Biomedical
Isotope Facility.
"Ironically, though the cyclotron was invented here, we (CFI) did not
have the dedicated small cyclotron our competitors around the world
had," he says. "I am very happy that this new facility is now here and
performing beautifully. The instrument and facility are a credit to the
laboratory staff who made it happen."
The centerpiece of the Biomedical Isotope Facility, which is located
adjacent to Bldg. 55, is a room-sized cyclotron built for Berkeley Lab
by a commercial company called CTI, headquartered in Knoxville. This
mini-cyclotron (the diameter of its magnet is only 90 centimeters) can
accelerate negative hydrogen ions to 11 MeV (million electron volts) of
energy. Once they attain peak energy, these negative hydrogen ions are
sent through a thin carbon foil to strip them of their electrons and
convert them into a beam of protons. This proton beam is then directed
into a target made up of a specific stable isotope in order to produce
a desired radioisotope. (Bombardment with energetic protons causes
target nuclei to release alpha particles or neutrons, converting the
nuclei to radioisotopes.)
"The system is designed to deliver fluorine-18, oxygen-15, nitrogen-13,
and carbon-11," says VanBrocklin. "These are the most common
positron-emitting isotopes for radio-pharmaceuticals."
VanBrocklin and his colleagues must work quickly with their
radioisotopes. The respective half-lives are 110 minutes for
fluorine-18, 20 minutes for carbon-11, 10 minutes for nitrogen-13, and
two minutes for oxygen-15.
Before a radioisotope can be used as a tracer, it must first be
incorporated into a pharmaceutical compound, a process called
"labeling." Fluorine-18, for example, is commonly attached to a type of
sugar to form "fluorodeoxyglucose." FDG is especially valuable for
studying the chemistry of the brain, the heart, and cancerous tumors.
Water labeled with oxygen-15 is an important blood flow tracer, and
ammonia labeled with nitrogen-13 is used as a tracer for heart
research.
Labeling a pharmaceutical compound entails transferring the isotopes
from the cyclotron into a lead-lined glovebox. The cyclotron at the
Biomedical Isotope Facility currently holds either gas or liquid
targets, which means that the isotopes can be siphoned through tubes
directly into the glovebox with no need of human handling.
"We have a collaboration with the Nuclear Science Division to develop
solid targets as well," says VanBrocklin. "This would require physical
handling of the radioisotopes but it would expand the array of isotopes
we can produce."
Once a radiopharmaceutical has been prepared inside a glovebox, it
again must be quickly put to use. An underground pneumatic tube system
linking the Biomedical Isotope Facility to CFI laboratories in Bldg. 55
can transport radio-pharmaceuticals between the two locations in eight
seconds.
"Because we're working with such small quantities of
radiopharmaceuticals, a fast and reliable means of transportation is
critical," says VanBrocklin.
The radioisotopes produced at the new facility will serve CFI
researchers in a variety of ways. VanBrocklin, who also heads CFI's
chemistry group, says he and his colleagues will continue their efforts
to develop new radioisotopes and biomedical tracers. They are currently
working with a fluorine-18 labeled compound called fluorometatyrosine,
which shows great potential for the study of Parkinson's disease.
The primary use of the Biomedical Isotope Facility's radioisotopes will
be in the CFI's two positron emission tomography (PET) machines. PET is
an imaging technique (pioneered in part at Berkeley Lab) whereby the
annihilation of radioisotope positrons localized in the body yields
photons that can be detected by a ring of crystals. This makes it
possible to observe otherwise invisible chemical processes in the human
body as they take place.
CFI houses the highest resolution PET scanner in the world, a
600-crystal ring with a spatial resolution of 2.6 millimeters and a
patient port that can accommodate a patient's head and neck. It also
harbors a 47-layer imaging system which can accommodate the entire
body. The addition of the Biomedical Isotope Facility is expected to
facilitate CFI's ongoing imaging studies of the brain and heart for
Alzheimer's disease and atherosclorosis, as well as its collaborative
research into cancer.
VanBrocklin gives credit to several individuals for helping to bring
the Biomedical Isotope Facility to Berkeley Lab. In addition to
Budinger and Chet Mathis (VanBrocklin's predecessor at the Lab), he
also cites chemists Jim O'Neal and Steve Hanrahan from his group.
The Biomedical Isotope Facility dedication ceremonies will be held at
10:30 a.m. on Aug. 30, in the Bldg. 55 parking area, adjacent to the
new facility.
During the week-long celebration of Berkeley
Lab's 65th Anniversary, scheduled to begin Aug. 26, there will be
another event to chronicle. On Friday, Aug. 30, the Laboratory will
dedicate the newest member of its family of facilities -- the
Biomedical Isotope Facility.