Measuring down to the smallest dose: gamma spectrometry enhances precision in radioligand therapy
New calibration service under development
Research into radioligand therapy requires results that are both accurate and easily comparable. But how can you reduce measurement uncertainty, especially at low doses? SCK CEN – together with its international partners – aims to answer that question by determining the activity using gamma spectrometry. This technique identifies radionuclides by their unique fingerprint. Meanwhile, the consortium has successfully completed two important experiments: one involving lutetium-177 and one carried out using actinium-225. These experiments represent an important step in the Precision Dosimetry Imaging Biomarker (PDIB) project, the intention of which is to develop a new, globally standardised calibration method.
The gamma spectrometry department at the nuclear research centre SCK CEN is home to no fewer than twenty high-purity germanium detectors. Those detectors have already been operating for years in connection with radiological monitoring and with the food chain in Belgium. “Each year, we analyse as many as 3000 to 3500 samples,” explained Leen Verheyen, an expert in gamma spectrometry. Those samples are very diverse, ranging from urine, which is analysed in order to detect internal contamination, to milk, soil and even sea water. “Right now, we are busy determining whether gamma spectrometry can also be used in nuclear medicine,” said Leen. “We want to be able to use it to measure the activity level in radiopharmaceuticals and to help calibrate measuring devices.”
Thanks to calibration, doctors and scientists around the world are able to refer to the same values. “This allows them to compare parameters such as the absorbed dose in tumour tissue and the response to treatment on an international level – according to the activity level administered,” said Clarita Saldarriaga Vargas, a dosimetry expert at SCK CEN. "Using gamma spectrometry, we can quantify kilobecquerels, which is especially useful in preclinical research, where we make use of very low doses.”
International calibration network
At SCK CEN, the gamma spectrometry department usually operates with an uncertainty level of around ten percent for its current applications. “In nuclear medicine, though, that's unacceptable," said Clarita, drawing a comparison to elite sports. “Take, for example, an elite athlete from Belgium who needs to eat 1 kilo of pasta. If an elite athlete in Spain is given the same instruction and receives 10% more pasta on his plate, comparing the sporting achievements of each athlete would be difficult. The same is true with radioligand therapy.”
The measurement uncertainty must therefore be kept below two percent, but that requires a strict, standardised measuring procedure. “That is something that we are developing with the PDIB consortium,” explained Leen. PDIB stands for Precision Dosimetry Imaging Biomarker: an international consortium that is being led by the Foundation for the National Institutes of Health in the United States of America. The measuring procedure takes a series of factors into account that could possibly affect the activity measurements. These include the positioning of the sample in the germanium detector, the type of vial in which the sample is stored, the volume we are measuring, the distance to the detector and the measurement time. The ultimate goal is to establish a network of secondary standards calibration laboratories.
Putting it to the test
In the meantime, the consortium has also put this to the test: are the various laboratories measuring the same values when using that same measuring procedure? In order to find out, it recently organised an inter-laboratory comparison. Each lab received two samples: one containing lutetium-177 and another with actinium-225. The measurement results were then compared to those determined by the National Physical Laboratory (NPL). That is one of the international references when performing nuclear calibrations. The calibration lab in the United Kingdom uses primary standards. “Our nuclear research centre achieved an excellent result with only a minimal deviation from the NPL,” she concluded. The difference between the SCK CEN measurement and the NPL measurement was less than 0,5% for both lutetium-177 and actinium-225.
The next stages of the process – in hospitals
The project partners also envisage a clinical application for the calibration technique, which they intend to develop during the next stage of the project. During that phase, each laboratory will prepare samples and send them to four hospitals in Europe. SCK CEN will be sending samples to the United Kingdom, France, Germany and the Czech Republic. The intention is for hospitals to use them to calibrate their radionuclide calibrators and SPECT scanners. They can calibrate the SPECT scanners by placing the samples in a cylindrical holder and sliding that phantom under the scanner. This project will be running until March 2028.
Purity
Gamma spectrometry offers an additional advantage, as it verifies the purity of radiopharmaceuticals in a single measurement. “Using gamma spectrometry, we can determine how much activity is contained in a sample, but also which radionuclides a sample contains,” says Leen. In order to establish this, the researchers place samples into germanium detectors. Those detectors convert incoming radiation into electrical pulses. “As each radionuclide emits radiation at specific gamma energies, a typical and recognisable peak in the gamma spectrum is created for each one. We could say that each peak represents the unique fingerprint of the particular radionuclide concerned,” continued Clarita. “In the case of radiopharmaceuticals, we need to achieve the highest level of purity possible, so we only wish to see one radionuclide appear on the spectrum.”
Preclinical research at SCK CEN
Gamma spectrometry is a valuable complement to the previous calibration technique, for which SCK CEN received accreditation. That technique allows us to operate in a range of between ten and hundreds of megabecquerels [MBq]. By combining both calibration techniques, the nuclear research centre SCK CEN is able to confirm the accuracy of its activity measurements.
Preclinical research at SCK CEN is also reaping the benefits of this. The increased measurement accuracy is a key advantage that is helping us to gain a better understanding of the biological mechanisms underlying radioligand therapy and to validate the precision and effectiveness of radiopharmaceuticals. This is vitally important, as that treatment can significantly improve the life expectancy and quality of life of cancer patients.
DDiissccoovveerr oouurr pprreecclliinniiccaall rreesseeaarrcchh
