Advances in Radionuclide Therapies for Neuroendocrine Tumor Liver Metastases

Abstract

Treating neuroendocrine tumor liver metastases is challenging, and extensive liver disease significantly impacts patient prognosis. Among various treatments, peptide receptor radionuclide therapy (PRRT) with lutetium-177-DOTATATE and radioembolization are used for inoperable cases. This thesis explores ways to enhance the effectiveness of these therapies. First, a randomized controlled trial (LUTIA) investigated intra-arterial injection of lutetium-177-DOTATATE into the hepatic artery. While safe, it showed no improvement in radiopharmaceutical uptake by liver metastases compared to standard administration. Second, a faster infusion protocol (5 minutes versus 30 minutes) for intravenous lutetium-177-DOTATATE was deemed safe without additional side effects. Third, two PET/CT parameters derived from gallium-68-somatostatin receptor imaging pre- and post-PRRT (SSTR-tumor volume and total lesion-SSTR) were significantly associated with time-to-new-treatment, though changes in these parameters did not predict time-to-new-treatment. Fourth, in a cohort treated with yttrium-90 radioembolization, a dose-response relationship was identified, recommending a minimum tumor dose of 150 Gy for optimal tumor response. Fifth, a study on residual activity in the administration system post-yttrium-90 radioembolization revealed minimal residual activity with thorough flushing. Lastly, combining PRRT and radioembolization using holmium-166 was found to be safe, showing comparable hematotoxicity to historical data.