Radioembolization with Intra-Arterial Angiotensin II to Improve Tumor-Absorbed Dose (RADIANT): A Single-Arm Phase II Study Protocol

Purpose: The effectiveness of transarterial radioembolization (TARE) depends largely on the tumor-to-non-tumor ratio (TNR): the ratio of microsphere concentration between tumor and non-tumorous liver tissue. Angiotensin II (AT-II) may improve TNR by inducing vasoconstriction primarily in arteries supplying healthy liver parenchyma. Tumor-feeding arteries, lacking neurovascular innervation, are largely unresponsive to AT-II, potentially resulting in preferential blood flow redistribution toward tumor tissue. The RADIANT study aims to evaluate whether intra-arterial AT-II infusion prior to yttrium-90 (90Y) microsphere injection improves tumor selectivity during TARE in patients with primary or metastatic liver tumors. Materials and Methods: This single-center, single-arm phase II study will include 15 patients with primary or metastatic liver tumors (any histological subtype, diameter ≥ 2 cm) referred for 90Y glass radioembolization. Each patient serves as their own control: during work-up, technetium-99m macroaggregated albumin (99mTc-MAA) is administered without AT-II and TNR is measured on SPECT/CT. During the therapeutic procedure, AT-II is infused intra-arterially (10 µg/min over 100 s) immediately before 90Y microsphere injection, and TNR is measured on post-treatment 90Y PET/CT. The primary endpoint is the TNR improvement factor (TNR after 90Y + AT-II divided by TNR after 99mTc-MAA). Secondary endpoints include toxicity and technical success of AT-II administration. Discussion: The RADIANT study will provide prospective evidence on the effect of intra-arterial AT-II infusion on tumor selectivity during 90Y radioembolization.