Development of a hybrid image-based method for bone marrow dosimetry during 177Lu-DOTATATE treatment

Abstract

Radionuclide therapy with 177Lu-DOTATATE is a well-established treatment for patients with advanced neuroendocrine tumors overexpressing somatostatin receptors. It is a generally well-tolerated treatment, but the kidneys and the bone marrow are dose-limiting organs. The aim of this thesis has been to develop a methodology for bone marrow dosimetry during treatment with 177Lu-DOTATATE and study the relationship between bone marrow absorbed dose and hematological toxicity. In Studies I and II, a planar image-based method for bone marrow dosimetry was developed, yielding bone marrow absorbed doses at 0.20 Gy/7.4 GBq that were significantly correlated to the hematological response. In paper three, the planar method was further developed into a hybrid planar and SPECT image methodology for a more personalized dosimetry using the activity concentrations in different sets of the thoracic and lumbar vertebrae. This resulted in bone marrow absorbed doses at 0.32-0.46 Gy/7.4 GBq, and stronger dose-response relationships compared to the planar method. It also highlighted the influence of bone metastases on the bone marrow absorbed dose and its correlation with hematological toxicity. An approach for estimation of bone marrow absorbed doses for patients with bone metastases was presented in Study IV. Assuming a specific uptake in the red marrow, a compartment model was incorporated to estimate the activity concentration in the specific and nonspecific uptakes in the red marrow and the activity concentration in infiltrating bone metastases. This approach resulted in increased correlations between absorbed dose to the red marrow and the response of platelets. Image-based methods for bone marrow dosimetry are feasible and demonstrate that an increased absorbed dose to the red marrow results in higher hematological toxicity. Dosimetry is one way to personalize PRRT, and accurate dosimetry methods are necessary to estimate the absorbed dose to both the targeted tumors and organs at risk to optimize the risk-benefit of the treatment.