Final PhD Oral Examination (Thesis Title: “Personalized Dosimetry Protocol for the Optimization of Lutetium-177 Dotatate Radionuclide Therapy”)

Abstract:
Targeted radionuclide therapy has been shown to be one of the most effective treatment options for metastatic neuroendocrine tumours (NETs). In particular, peptide receptor radionuclide therapy (PRRT) with Lutetium-177 (177Lu) labeled DOTATATE results in significantly improved tumour control, while only low to moderate normal tissue toxicity. There is growing evidence that the efficacy of this treatment can be further improved by performing personalized administration of radiopharmaceutical. However, since dosimetry for PRRT is usually considered challenging, traditionally NET patients are treated with same or very similar amounts of 177Lu DOTATATE. The objective of this thesis was to propose a simple, yet accurate dosimetry protocol, which could be easily implemented in clinics for the optimization of 177Lu DOTATATE radionuclide therapy. To achieve this aim, the following physics questions, that are related to image-based dose calculation, were investigated:

The performance of camera calibration method using simple planar scans, was compared to that obtained from tomographic acquisitions. To assess the quantitative accuracy of commercial SPECT reconstruction software (Siemens Flash3D), a number of phantom experiments with different photon attenuation conditions were performed. The influence of camera dead-time correction on the estimated dose was investigated. The kidney doses obtained from four time-activity curve creation methods using three data points were compared. In order to simplify the dosimetry, the accuracy of dose estimated based on two data points, or even potentially one data point, was evaluated.

Our results show that gamma camera can be accurately calibrated with planar scan of a point-like source. The error of 177Lu activity quantification in large volume (>100mL) was about 5% when proper segmentation was applied to Siemens Flash3D reconstructions. Dead-time correction was found to have no impact on the estimated dose. Kidney dose estimated based on single data measured at 48-72 hours produced small error (<10%) for the majority of patients, thus could be recommended for clinical use. This single data point method can also be applied to other organ, as long as its bio-kinetics can be described by a monoexponential function and the statistical behavior of the population effective half-lives in that organ has been estimated.