Endoscopic Ultrasound-Guided Brachytherapy of Yttrium-90 Implantation Into Pancreas: A Dose-Escalation Pilot Study

Abstract

Intratumoral brachytherapy enables higher dose treatment and reduces damage to adjacent tissues. We first validated the feasibility and safety of endoscopic ultrasound (EUS)-guided Yttrium-90 (⁹⁰Y) microspheres implantation in a porcine model. Under EUS guidance, ⁹⁰Y-loaded microspheres were implanted into the pancreas of 10 miniature pigs. The first pig was implanted with 10 MBq particles. Subsequently, nine pigs were sequentially included in the low- (20 MBq), medium- (40 MBq), and high-dose (60 MBq) groups. Positron emission tomography (PET)/CT imaging was used to check the occurrence of particle displacement postoperatively. After euthanasia, the pancreas and adjacent organs were excised for histological examination and residue radiation detection. The absorbed doses demonstrated safe in the porcine model were further in the xenograft model and KRAS^LSL/+Trp53^FL/FLPtfqa^Cre/+ mouse model. EUS-guided implantations of ⁹⁰Y-loaded microspheres were successful in all animals. Two pigs had mild serum amylase elevation in the high-dose group and the abnormal index returned to baseline without interventions. The volume of necrotic lesions ranged from 255.76 to 745.57 mm³. In KPC mouse model, PET/CT imaging demonstrated a significant decrease in maximum standardized uptake value (SUVmax) after ⁹⁰Y implantation. EUS-guided ⁹⁰Y-loaded carbon microsphere implantation could serve as a safe and feasible technique at ultrahigh dose for pancreatic cancer brachytherapy.