Clinical application of quantitative spect in patient specific dosimetry and beta cell quantification

Abstract

This thesis demonstrates how, despite different challenges, quantitative analysis of single photon emission computed tomography (SPECT) images, facilitates in answering specific clinical questions that cannot (yet) be answered with another method. First, different technical and practical challenges are discussed. Currently, most technical challenges can be counteracted by using advanced reconstruction protocols enabling attenuation, scatter and collimator correction. Then, different methods for calculation of bone marrow radiation doses (including one SPECT-based method) were used, and results were compared to the bone marrow toxicity in order to select a method for prediction of bone marrow toxicity. This showed that the SPECT-based dosimetry seemed to be most predictive. Quantitative analysis of SPECT images was also applied for characterization of the amount of pancreatic beta cells. Beta cells are the insulin producing cells in the pancreas and play a key role in diabetes. To facilitate future research on the pathophysiology and treatment of diabetes, radiolabeled exendin was developed. Exendin specifically targets the glucacon-like-1 (GLP-1) receptor, expressed on beta cells, and the radiolabel can be visualized with a SPECT camera. Therefore this can be used for in vivo beta cell quantification. This was applied in a preclinical study, in ten type 1 diabetes patients, and in ten healthy controls. To optimize SPECT acquisition and reconstruction protocols, a phantom was developed for mimicking the human images. From these studies we conclude that from a biological perspective the uptake can be used as a measure for the beta cell mass and we demonstrated that uptake in the healthy individuals and patients with diabetes is in line with the expected variation in beta cell mass, and the expected differences between these groups. Finally, different methods for dosimetry and quantification of radioactivity distribution were applied to calculate the radiation dose to the beta cells as a result of imaging with radiolabeled exendin. This showed that doses remain below the levels at which toxicity is expected. Altogether, this work demonstrates that although we face numerous challenges in quantitative use of SPECT images, the applications are so valuable for answering different clinical questions, that it is worthwhile to tackle them.