Fluorine-18 Substitute Identified for PET Machine Calibration

As the number of positron emission tomography (PET) procedures continues to increase, so too does the need for more precise calibration of PET machines, enabling accurate and comparable measurements from center to center, patient to patient and in the same patient over time.

Growth in the number of positron emission tomography (PET) procedures—estimated at 20 percent annually—has prompted the need for more precise calibration of PET machines. The National Institute of Standards and Technology (NIST) recently standardized germanium-68 as a calibration substitute in order to develop a functional measurement standard for fluorine-18.

Surveys by both private and public sector groups estimate growth in the number of PET procedures at about 20 percent annually—some 650,000 procedures were performed in 2003, with 2.1 million predicted for 2010.

The very short half-life—just two hours—of fluorine-18 makes it ideal for use in patients undergoing PET procedures but impossible to use to calibrate machines, as precisely measured sources made by a single central lab would decay in the time it took to distribute them to distant imaging centers.

Enter germanium-68, a radioisotope with similar energy decay characteristics to fluorine-18, but a 271-day half-life. The National Institute of Standards and Technology (NIST) recently standardized germanium-68 as a calibration substitute in order to develop a functional measurement standard for fluorine-18.

"Measurement standards are very helpful to quality control, which is critical to quantitative scanning," said Steven M. Larson, M.D., chief of nuclear medicine service and vice-chair of research in the Department of Radiology at Memorial Sloan-Kettering Cancer Center in New York. "We need to set standards that do not vary day by day and week by week. Germanium-68 is perfect for that purpose. We are able to use it for a long period of time and be assured that the scanning is going to be the same from one week to the next."

All Instruments Calibrated Against Common Standard

"Germanium-68 can never be used for patients studies because the half-life is too long, but it can be used to calibrate instruments as long as we know the correction factors necessary to make a comparison measurement between fluorine-18 and germanium-68," said Brian E. Zimmerman, Ph.D., research chemist and project leader for nuclear medicine standards at NIST. "This makes it possible to calibrate all instruments in the clinics against a common standard."

Cobalt-57, used in lieu of technetium-99m, is an example of another calibration surrogate used in radiology.

In 2007, NIST produced a national radioactivity standard for germanium-68 with an uncertainty of 0.3 percent. "This will be the first time that a calibrated source of germanium-68 will be available that can be directly traced back to an original NIST measurement," said Dr. Zimmerman.

RadQual, LLC, of Concord, N.H., has developed and patented a calibration source based on the NIST germanium-68 standard, a dose calibrator designed to mimic a 5 ml syringe filled with 3 ml of fluorine-18. RadQual established traceability to NIST to verify that its sources are related to a single standard correlating to the national standard of germanium-68. RadQual expects to start accepting orders for delivery of these sources in September.

PET Phantom is Next Step

Whole-body FDG PET scans. Posterior (left) to anterior (right) adjacent selected coronal images are displayed. Abnormal FDG-avid lesions include primary rhabomyosarcoma in the right thigh (arrowheads; maximum SUV, 7.4) and a smaller lesion in the distal left medial femoral diaphysis (arrows; maximum SUV, 3.1). Radiology 2007; 243:288–292. © RSNA, 2007. All rights reserved. Reprinted with permission.

NIST is now working to develop a germanium-68 PET phantom, to be used not only for dosimetry but also for constancy checks and characterization of scanners used in clinical trials.

"I think that the capability of having a long-lived standard, or substitute standard, for fluorine-18 will provide more consistent data throughout clinical trials and through the course of patient treatment," said Dr. Zimmerman. "Calibrating sources for use in phantoms could give the FDA more confidence in the data from sites participating in clinical trials of a new drug and using imaging data as a benchmark for treatment performance."

NIST also plans to develop calibrated sources into a form that can be used for combined PET/CT scans, with even more ambitious plans to do the same for combined PET/MR.

"There is much more work to do," said Dr. Zimmerman. "We are still detailing the exact differences between measurements of fluorine-18 and germanium-68. We have a new set of experiments planned for this summer."

The quantitative nature of instrumentation is very important to the future of molecular imaging research, said Dr. Larson, who also serves as a member of the RSNA News Editorial Board.

"I think germanium-68 is a very valuable radiotracer that will be useful in the future for many different radiopharmaceuticals, which can be used without the need to involve a cyclotron in the production process," he said. "The continuing production and availability of germanium-68 in significant quantity is something we hope will be assured, since it must be made in a very large cyclotron found only at the national laboratories."