Intra-arterial Peptide Receptor Radionuclide Therapy using ⁹⁰Y DOTATOC for Hepatic Metastases of Neuroendocrine Tumors

Abstract

Background: Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determine whether hepatic intra-arterial (IA) injection of ⁹⁰Y-DOTATOC Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than intravenous (IV) injection, thus maintaining efficacy while reducing systemic toxicity. Methods: PRRT-naïve adult NET patients with liver-dominant metastases involving <70% of the liver were enrolled in a prospective pilot, single-center, open-label study. Patients underwent baseline PET/CT imaging using IV ⁶⁸Ga-DOTATOC. 94.7±5.4 mCi ⁹⁰Y-DOTATOC was administered into the proper hepatic artery over 30 minutes. The first five patients received IA ⁶⁸Ga-DOTATOC and underwent PET/CT imaging after completion of treatment. All patients were followed for response (RECIST 1.1) and toxicity (CTCAE v4.0). Results: Of 10 enrolled patients, 30% of patients (3/10) experienced grade 3 adverse events (AEs), which were not attributed to ⁹⁰Y-DOTATOC treatment. Two patients died within 6 months of IA therapy, though these deaths were not clearly associated with treatment. During the follow-up period, best response was Stable Disease (SD) in 70% (7/10) and Progressive Disease (PD) in 20% (n = 2/10), with an additional patient developing PD during the optional 1-year followup period. No Partial Response (PR) or Complete Response (CR) was observed. Patients who received IA ⁶⁸Ga-DOTATOC failed to demonstrate increased uptake by hepatic metastases compared to IV, with median IA:IV SUV_max ratio of 0.81 (range 0.36-2.09) on a lesion level and ratio 0.90 (range 0.54-0.97) on a patient level. However, extrahepatic metastases and uninvolved organs demonstrated decreased uptake with IA compared to IV infusion (IA:IV ratio 0.68±0.19). Conclusion: Our study demonstrated that a single IA administration of PRRT resulted in minimal disease response. In addition, in contrast to previous reports, there was no increased uptake of ⁶⁸Ga-DOTATOC in hepatic metastases when delivered IA compared to IV routes of administration. One possible reason is somatostatin receptor saturation, as the imaged ⁶⁸Ga-DOTATOC was administered alongside a much larger mass dose of ⁹⁰Y-DOTATOC than diagnostic doses used in prior studies.