Intra-Arterial Peptide Receptor Radionuclide Therapy (PRRT) with Lutetium (¹⁷⁷Lu) DOTATATE for Neuroendocrine tumour Liver dominant metastatic disease -Initial experience

Introduction: Hepatic metastases, with neuroendocrine tumors (NETs), have an adverse impact on the patient’s quality of life and survival, especially in patients with refractory, unresectable, or recurrent disease. Transcatheter intra-arterial (IA) liver directed therapies, such as hepatic artery embolization, chemoembolization, and radioembolization are frequently used in patients. Peptide receptor radionuclide therapy (PRRT) is now well established as treatment modality of somatostatin receptor (SSTR) expressing neuroendocrine tumors. Commonly practiced treatment protocol consists of multiple cycles of intravenous administration, however, in patients with liver dominant metastases there are issues of reduced tumor targeting and reduced survival. Intra-arterial administration of ¹⁷⁷Lu-DOTATATE is an alternative novel technique aiming higher absorbed tumor dose in targeted liver lesions and to increase overall survival. The present study presents initial experience of intra-arterial administration of ¹⁷⁷Lu-DOTATATE in patients with Neuroendocrine tumour liver dominant metastatic disease at our institution. Materials and Methods: Retrospective analysis was performed for 10 NET patients (M 31, F 24; mean age 52 y) with SSTR expressing liver metastases, who received single cycle of Intra-arterial ¹⁷⁷Lu-DOTATATE (mean administered activity: 7.2 GBq of Lu-177) during June 2019- Oct 2019. Intra-arterial microcatheter was placed in hepatic artery and the activity was administered into the right and left hepatic artery in proportion to the tumor burden of the respective liver lobe. Whole body ¹⁷⁷Lu-DOTATATE planar scans were obtained at 2, 24 and 96 hrs post therapy. Tumor to non-tumor ratios in liver lesions was obtained in each case. The symptomatic, biochemical (Chromogranin A) and objective imaging response (Ga-DOTANOC PET/CT) was assessed 3 months post-PRRT in all patients.

Results: Symptomatic responses and better quality of life were observed in all the 11/11 (100%) patients. Biochemically, partial response was seen in 8/11 (72.7%), stable values were seen in 2/11 (18.1%), and progression of tumor marker was seen in 1/11 (9.2%) patient. On the post therapy ⁶⁸Ga-DOTANOC PET/CT scan, 8/11 patients (72.7%) demonstrated partial response, 2/11 stable disease (18.1%), and 1/11(9.2%) progressive disease (disease progression was seen at sites other than targeted liver lesion). Tumor to non tumor dose ratios in targeted liver lesions were in the range of 5.5 - 25 at 96 hrs. No significant adverse events were observed during and post IA administration.

Conclusions: High objective response (90.9%), with no significant adverse events were obtained in these patients post single IA administration. Intra-Arterial administration of the radiopeptide in patients with NET liver metastases seems to be a promising approach of PRRT for liver dominant metastatic disease.