You can measure the distribution of your drug and uptake in your tissue of interest and other organs with molecular imaging. More specifically, with positron emission tomography (PET) you can accurately measure the uptake of your radiolabeled drug in tissues. The quality of this data highly depends on the calibration and standardization of your PET scanner. Especially in multicenter trials.
Quantification of PET scans.
Quantitative analysis of a PET scan measures the accumulation of your tracer in your target tissue and non-target tissues. It provides you with target quantification of for instance your new drug candidate. This is in stark contrasts with visual assessment of PET images, where you only get subjective data on tracer distribution.
Quantification of PET scans and standardized uptake values (SUVs).
You can quantify PET scans by measuring standardized uptake values (SUVs). To measure the SUV, you first measure the concentration of the radioactivity in the target lesion or organ. Next, you correct the radioactivity concentration by the amount of radioactivity administered to the patient. Lastly, you correct for the body weight of the patient.
In principle, you can compare the SUV outcomes of different patients from different imaging sites. However, differences in image acquisition, reconstruction and data analysis procedures can influence SUV results (Figure 1). If you want to compare SUV results from multicenter studies, you need to keep this variability in mind. It also means you need to take action to reduce the variation in image quality and quantification between imaging sites.
Figure 1. Effect of different reconstruction methods on SUV results. Available from: Standardisation of FDG PET/CT imaging for tracer uptake quantification and automated metabolic volume assessment by Ronald Boellaard.
So, how can you solve the SUV variability problem? Boellaard et al. established a protocol for standardization of quantitative fluorodeoxyglucose F-18 (FDG) whole body PET studies. This protocol aims to achieve interchangeability of SUVs between imaging sites. They present recommendations on amongst others patient preparation, the administration procedure, FDG dose, acquisition procedure, data analysis procedures, SUV normalizations and quality control measures. In this blog, we focus on quality control measures as this is the most essential procedure to overcome the SUV variability problem.
Quality control and calibration of PET scanners.
One of the key factors for reproducible PET acquisition and quantification is your PET scanner. That’s why your PET scanner should always be in optimal condition. This makes proper quality control and calibration of your PET scanner extremely important.
First, you should perform a daily PET quality control procedure according to the manufacturer’s recommendations. This way you assess if your PET system is functioning correctly. Second, you have to cross-calibrate the PET scanner against a dose calibrator. Do keep in mind that the SUV calculation includes the dose administered to the patient. Therefore, you should use the dose-calibrator, where you measure the administered dose to the patient, for the cross-calibration of your scanner.
Have you completed these two steps successfully? Then your PET scanner is in good shape. However, it does not assure that the measurements are comparable between imaging sites. To achieve this, you have to perform a calibration of your scanner with a specific phantom. The phantom consists of spheres of various sizes that are placed in a torso-shaped container. You fill the spheres and container with radioactivity according to a standardized protocol. You can now scan the phantom, reconstruct the images, and measure the SUV in the spheres.
By dividing the measured radioactivity concentration in the PET images with the radioactivity concentration inserted in the spheres you determine the recovery coefficients. The next step is to use these coefficients to compensate for differences in outcome of the quantitative analysis of PET images. When you perform this calibration according to the European guidelines (EARL) you will receive accreditation. This shows that your scanner’s performance meets the quality standards.
Quality data for quality drug development decisions.
In short, the quality of your PET imaging data relies on the calibration and standardization of the PET scanner across all your clinical trial sites. With differing quality standards in a multicenter trial, you gather unreliable data. It could lead to making the wrong decisions for the future development of your drug.
This blog is based on a published manuscript by Boellaard et al. in the European Journal of Nuclear Medicine and Molecular Imaging.