177Lu-DOTA-octreotate Radionuclide Therapy of Neuroendocrine Tumours : Dosimetry-Based Therapy Planning and Outcome

• Peptide receptor radionuclide therapy for the internal radiation of neuroendocrine tumours expressing somatostatin receptors has made great advances and offers promising results. 177Lu-DOTA-octreotate is one of the most widely used radiopeptides, but kidneys and bone marrow are organs at risk. Methods of measuring radiation doses to at-risk organs and tumours (dosimetry) on an individual patient basis have been regarded as impracticable and a maximum of 4 treatment cycles has widely been accepted as the treatment standard instead.The first aim of this thesis was to establish a clinically feasible protocol to calculate absorbed doses to bone marrow and the kidneys during therapy with 177Lu-DOTA-octreotate. A new dosimetry protocol for the bone marrow was described. Dosimetry for solid organs had previously been described based on 3-dimensional imaging by the research group. In the current thesis it was demonstrated that in most patients only minor changes of the effective half-life occurred in the kidneys. By performing complete dosimetry during the first cycle and comparing it with the uptake in later cycles, it was shown that the absorbed dose can be cal-culated based on the activity concentration at 24 hours after therapy. The study concluded that 50% of all patients could receive more than the standard 4 treatment cycles with 7.4 GBq 177Lu-DOTA-octreotate without passing the limit of 23 Gray to the kidneys or 2 Gray to the bone marrow, whereas 20% would tolerate fewer than 4 cycles. The second aim was to describe treatment outcomes of dosimetry-guided therapy with 177Lu-DOTA-octreotate. Patients with metastasized colorectal neuroendocrine tumours and bronchial carcinoids were shown to have longer survival with this method than previously reported. Morphological tumour response could be correlated to time to progression. Furthermore, in a case of low-differentiated neuroendocrine cancer it was shown that large tumours with high proliferation can also be treated with this method and that tumour-to-risk organ ratios can improve in later cycles, resulting in a more effective treatment.Dosimetry-guided, fractionated radionuclide therapy with 177Lu-DOTA-octreotate is a valuable treatment option for patients with advanced neuroendocrine tumours expressing somatostatin receptors.

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