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

Introduction: The quality control parameters of in-house-produced 90Y-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 90Y-DOTATATE in acceptable radiochemical purity (RCP), with expected pharmacological behavior in in vivo models, establish the quality of 90Y-Acetate. Clinical translation of 90Y-Acetate in formulation of 90Y-DOTATATE adds support toward its use as clinical-grade radiochemical. Methods: Quality control parameters of 90Y-Acetate, namely radionuclide purity (RNP), were evaluated using ß- spectrometry, γ-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 90Y-Acetate as an active pharmaceutical ingredient radiochemical was ascertained by radiolabeling with DOTATATE. In vivo biodistribution of 90Y-DOTATATE was carried out in nude mice bearing AR42J xenografted tumor. Clinical efficacy of 90Y-DOTATATE was established after using in patients with large-volume neuroendocrine tumors (NET). Bremsstrahlung imaging was carried out in dual-head gamma camera with a wide energy window setting (100-250 keV). Results: In-house-produced 90Y-Acetate was clear, colorless, and radioactive concentration (RAC) in the range of 40-50 mCi/mL. RCP was >98%. 90Sr content was <0.85 µCi/Ci of 90Y. Gross λ content was <0.8 nCi/Ci of 90Y and no γ peak was observed. Fe3+, Cu2+, Zn2+, Cd2+, and Pb2+ contents were <1.7 µg/Ci. The radiolabeling yield (RLY) of 90Y-DOTATATE was >94%, RCP was >98%. The in vitro stability of 90Y-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 90Y-DOTATATE in tumor region. Conclusions: This study demonstrates that the in-house-produced 90Y-Acetate from HLLW can be used for the formulation of various therapeutic 90Y-based radiopharmaceuticals. Since 90Y is an imported radiochemical precursor available at a high cost in India, this study which demonstrates the suitability of indigenously sourced 90Y, ideally exemplifies the recovery of "wealth from waste." The Clinical Trial Registration number: (P17/FEB/2019).

Extraction paper chromatography technique for the radionuclidic purity evaluation of 90Y for clinical use.

Yttrium-90 used for therapy should be of very high radionuclidic (RN) purity (>99.998%) as the most probable contaminant, strontium-90, is a bone seeker with a maximum permissible body burden of 74 kBq (2 microCi) only. None of the current known methods of RN purity estimations is adequate to reliably measure the 90Sr RN impurity at such low levels. Our aim was to develop a reliable technique to accurately determine the amount of 90Sr in 90Y used for therapy. This new technique combines chelate-based extraction with paper chromatography using paper impregnated with 2-ethylhexyl, 2-ethylhexylphosphonic acid (KSM-17), which is a 90Y-specific chelator. A PC strip impregnated with KSM-17 at the point of spotting is used for chromatography. Upon development with normal saline, 90Sr moves to the solvent front leaving 90Y completely chelated and retained at the point of spotting. The activity at the solvent front (90Sr) is quantified by liquid scintillation counting, and the data are compared with the total applied activity to provide the RN purity of the test solution. The method has a sensitivity of > or =74 kBq (2 microCi) of 90Sr per 37 GBq (1 Ci) of 90Y. This novel, innovative, and simple technique offers a reliable solution to the unanswered problem of estimation of 90Sr content in 90Y used for cancer therapy.