[225Ac]Ac-DOTATATE Alpha Therapy Shows Promising Symptomatic Response in Progressive NETs Post-[177Lu]Lu-DOTATATE

For patients with metastatic neuroendocrine tumors (NETs), [177Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is a standard second-line treatment. While effective, many patients eventually experience progressive disease (PD) after an initial response or stabilization. This creates a critical need for salvage therapies to manage disease progression and improve patient outcomes. The study addresses this gap by comparing two salvage options: retreatment with [177Lu]Lu-DOTATATE or a more potent targeted alpha therapy, [225Ac]Ac-DOTATATE, which delivers higher linear energy transfer.

This retrospective, single-institution observational study analyzed 40 metastatic NET patients (20 per arm) who had progressed after an initial course of [177Lu]Lu-DOTATATE PRRT (4-6 cycles) with an objective response or stable disease. Patients were divided into two arms based on salvage treatment: Arm A received [225Ac]Ac-DOTATATE and Arm B received salvage [177Lu]Lu-DOTATATE. Baseline characteristics were matched across groups, including primary disease site, WHO grading, Ki-67 index, and [18F]F-FDG avidity. Treatment response was evaluated across three categories: symptomatic, biochemical, and functional/anatomic imaging using RECIST 1.1 criteria.