Quantification Methods for Clinical Studies in Nuclear Medicine - Applications in AMS, PET/CT and SPECT/CT

An essential part of the development of new radiopharmaceuticals for use in diagnostic nuclear medicine is the determination of its biokinetic properties. The uptake and turn-over of the radiopharmaceutical in the source organs is of great interest since this could determine whether the radiopharmaceutical would be suitable for clinical use or not. It is also important that the biokinetics and dosimetry of the radiopharmaceuticals is thoroughly investigated in order to determine the radiation absorbed doses to various organs and tissues and the effective dose. This is done to evaluate the radiation risks, which is one of the risks factors that have to be compared, with the benefits of their use. Modern imaging systems such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) have limitations that complicate the accurate estimation of the activity content in source organs, and thus also the estimation of the radiation absorbed dose, to organs and tissues of the human body. As an example, the partial volume effect poses significant problems with the reliability of the activity values when imaging small volumes. Drawing regions of interest smaller than the actual structure could influence the results. With large ROIs, the activity concentration has been shown to be underestimated by 70 % for a 0.5-ml sphere and 31 % for a 20-ml sphere. With small ROIs the underestimation ranges from 66 to 16 % (Paper II). PET is becoming more common in radiotherapy treatment planning and also used to monitor treatment response. In these cases, as well as in planning of surgery, it is important that the volume of the structure of interest is estimated accurately. Using phantoms with fillable, hollow, plastic spheres in an active background for estimation of the volume reproducing threshold would lead to overestimation of the tumour volume. The background dependence seen when using plastic phantoms is not present when using gelatin phantoms without walls (Paper III). As new imaging modalities are introduced, the measurement procedures and outline of clinical studies have to be adjusted to make use of the full potential of these new techniques. Biokinetic studies have commonly been performed using planar gamma camera images and the use of the conjugate view technique. As SPECT is very common at nuclear medicine clinics today, the use of this new and supposedly more accurate technique for determination of the biokinetics of radiopharmaceuticals is a natural step in the development process. It was shown that the organ dose estimations differed significantly when using complementary SPECT/CT measurements to quantify activity in the organs (i.e. to conduct dosimetry measurements) than when using planar images alone (Paper I). In drug development, accelerator mass spectrometry (AMS) has become an important tool for quantifying the content of 14C-labelled drug molecules in biological samples and to determine the pharmacokinetics of promising new drugs. PET or SPECT can be used simultaneously with AMS for analysis of the behaviour of the same compound labelled with positron (PET) or photon (SPECT) emitting radionuclides. The information acquired from the different modalities is complementary i.e. AMS gives information about the pharmacokinetic profile in blood and urine and PET and SPECT gives information about the pharmacokinetic behaviour in organs and tissues. The human microdosing concept is aiming to speed up drug development and reducing the costs by improved candidate selection in early drug development. In order to promote the use of AMS for analysis of biomedical samples, a fast and easily implemented sample preparation method is needed, which converts the biological samples to solid graphite. The precision of such a method, which is developed in Paper IV, is lower that earlier more time-consuming methods, but it is well suited for this type of application. In order to facilitate the implementation of the AMS technique closer to the clinics, the development of smaller AMS systems is a constantly ongoing process. When comparing high-voltage AMS with low-voltage AMS it is shown that the AMS instruments themselves were comparable and that low voltage AMS provides a good alternative to the larger and more expensive high-voltage tandem AMS systems (Paper V).