On the Separation of Yttrium-90 from High-Level Liquid Waste: Purification to Clinical-Grade Radiochemical Precursor, Clinical Translation in Formulation of⁹⁰Y-DOTATATE Patient Dose

Abstract

Introduction: The quality control parameters of in-house-produced 90 Y-Acetate from high-level liquid waste (HLLW) using supported liquid membrane (SLM) technology were validated and compared with the pharmacopeia standard. The radiolabeling of DOTATATE yielding 90 Y-DOTATATE in acceptable radiochemical purity (RCP), with expected pharmacological behavior in in vivo models, establish the quality of 90 Y-Acetate. Clinical translation of 90 Y-Acetate in formulation of 90 Y-DOTATATE adds support toward its use as clinicalgrade radiochemical. Methods: Quality control parameters of 90 Y-Acetate, namely radionuclide purity (RNP), were evaluated using bspectrometry, c-spectroscopy, and liquid scintillation counting. RCP and metallic impurities were established using high-performance liquid chromatography and inductively coupled plasma optical emission spectrometry, respectively. The suitability of 90 Y-Acetate as an active pharmaceutical ingredient radiochemical was ascertained by radiolabeling with DOTATATE. In vivo biodistribution of 90 Y-DOTATATE was carried out in nude mice bearing AR42J xenografted tumor. Clinical efficacy of 90 Y-DOTATATE was established after using in patients with large-volume neuroendocrine tumors (NET). Bremsstrahlung imaging was carried out in dualhead gamma camera with a wide energy window setting (100-250 keV). Results: In-house-produced 90 Y-Acetate was clear, colorless, and radioactive concentration (RAC) in the range of 40-50 mCi/mL. RCP was >98%. 90 Sr content was <0.85 lCi/Ci of 90 Y. Gross k content was <0.8 nCi/Ci of 90 Y and no c peak was observed. Fe 3+ , Cu 2+ , Zn 2+ , Cd 2+ , and Pb 2+ contents were <1.7 lg/Ci. The radiolabeling yield (RLY) of 90 Y-DOTATATE was >94%, RCP was >98%. The in vitro stability of 90 Y-DOTATATE was up to 72 h postradiolabeling, upon storage at -20°C. Post-therapy (24 h) Bremsstrahlung image of patients with large NET exhibit complete localization of 90 Y-DOTATATE in tumor region. Conclusions: This study demonstrates that the in-house-produced 90 Y-Acetate from HLLW can be used for the formulation of various therapeutic 90 Y-based radiopharmaceuticals. Since 90 Y is an imported radiochemical precursor available at a high cost in India, this study which demonstrates the suitability of indigenously sourced 90 Y, ideally exemplifies the recovery of ''wealth from waste.'' The Clinical Trial Registration number: (P17/FEB/2019).

NGHIÊN CỨU TÁCH ĐỒNG VỊ PHÓNG XẠ 90Y TỪ NGUỒN 90Sr/90Y BẰNG KỸ THUẬT THẤM CHỌN LỌC QUA MÀNG POLYTETRAFLUOROETHYLENE TẨM DUNG MÔI PC88A

“…Điều chế 90 Y từ 90 Sr/ 90 Y dùng trong điều trị bệnh bằng phương pháp tách chọn lọc qua màng đã thấm chất chiết đặc hiệu là PC88A có thể là chiến lược lâu dài vì nguồn 90 90 Sr trong dung dịch 90 Y luôn < 0,001% [2,6]. Hơn nữa, kết quả tạo ra dạng 90 Yacetate với nhiều thuận lợi: Hiệu suất tách hơn 90% và kim loại nặng trong sản phẩm dưới mức cho phép [5,7], dễ dàng đánh dấu với các phân tử sinh học để sử dụng điều trị trên lâm sàng mà không cần phải ủ với đệm acetate 0,5 M như 90 YCl 3 [5,6].…”