Given the high frequency of liver
metastases in
neuroendocrine tumor patients, we aimed to determine whether hepatic intraarterial administration of
90Y-DOTATOC peptide receptor radionuclide therapy (PRRT) would increase treatment efficacy while reducing systemic toxicity compared with systemic toxicity from
intravenous administration as previously reported in the literature. Methods: PRRT-naïve adult
neuroendocrine tumor patients with liver-dominant
metastases were enrolled in a prospective single-center, open-label pilot study. The patients underwent baseline PET/CT using intravenous
68Ga-DOTATOC. Then, 3.5 ± 0.2 GBq (94.7 ± 5.4 mCi) of
90Y-DOTATOC were administered into the proper hepatic artery over 30 min. The first 5 patients also received intraarterial
68Ga-DOTATOC and underwent PET/CT. All patients were followed for response (RECIST, version 1.1) (primary aim 2, safety) and toxicity (Common Terminology Criteria for Adverse Events, version 4.0) (primary aim 1, efficacy) for at least 6 mo, with optional follow-up for up to 1 y. In the subset of 5 patients who underwent both intravenous and intraarterial
68Ga-DOTATOC PET/CT,
tumor SUVmax was compared between intravenous and intraarterial administration for hepatic
tumors, intrahepatic
tumors, and uninvolved background organs (secondary aim, intravenous vs. intraarterial uptake). Results: The study was terminated after a planned analysis of the first 10 patients because of lack of efficacy. The best response was stable disease in 90% (9/10 patients) and progressive disease in 10% (1/10 patients) at 3 mo, and stable disease in 8 of 10 patients and progressive disease in 2 of 10 patients at 6 mo. One additional patient developed progressive disease after the 6-mo follow-up period but within the optional 1-y follow-up period. No partial response or complete response was observed. The 2 patients with the highest liver
tumor burden died within 6 mo of treatment, with treatment considered a possible contributor. Patients who received intraarterial administration failed to demonstrate higher uptake by hepatic
metastases than patients who received
intravenous administration, with a median intraarterial-to-intravenous SUVmax ratio of 0.81 (range, 0.36-2.09) on a lesion level. Conclusion: Our study found that administration of PRRT via the proper hepatic artery did not reproduce the increase in hepatic
tumor uptake that was previously reported. In addition, the single treatment using
90Y-DOTATOC did not induce
tumor shrinkage, indicating that more treatment cycles may be required. Possible safety concerns in patients with a high liver
tumor burden should inform patient selection for future studies.