Biomedical Imaging to be Extended by New Biomedical Isotope Facility

August 16, 1996

By Lynn Yarris, LCYarris@LBL.gov


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.

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.