Background: Lutetium-177-DOTA-octreotate ( 177 Lu-DOTATATE) significantly increases survival and response rates in patients with grade I and grade II neuroendocrine tumors (NETs). However, survival and response rates are significantly lower in patients with bulky liver metastases. Increasing the tumor-absorbed dose in liver metastases may improve response to 177 Lu-DOTATATE. The LUTIA (Lutetium Intra-Arterial) study aims to increase the tumor-absorbed dose in liver metastases by intra-arterial (IA) administration of 177 Lu-DOTATATE, compared to conventional intravenous (IV) administration.Methods: A multicenter, within-patient randomized controlled trial (RCT) in 26 patients with progressive, liverdominant, unresectable grade I or grade II NET will be conducted. Patients with bilobar bulky disease will be randomly allocated to receive IA treatment into either the left or the right hepatic artery. Using this approach, one liver lobe will be treated intra-arterially (first-pass effect), while the contralateral lobe will receive an intravenous treatment as a second-pass effect. The primary endpoint of this study is the difference in tumor-to-non-tumor ratio of 177 Lu-DOTATATE uptake between the two liver lobes on post-treatment SPECT/CT (IA versus IV). Secondary endpoints include absorbed dose in both liver lobes, tumor response, dose-response relationship, toxicity, uptake in extrahepatic lesions, and renal uptake. Discussion: This multicenter, within-patient RCT will investigate whether IA administration of 177 Lu-DOTATATE results in a higher activity concentration in liver metastases compared to IV administration. Trial registration: ClinicalTrials.gov, NCT03590119. Registered on 17 July 2018.