A PLC based semi-automated extraction chromatographic separation system for the isolation of medical grade no-carrier-added lutetium-177 for targeted cancer therapy

Abstract

Extensive clinical deployment of lutetium-177 (¹⁷⁷Lu) radiopharmaceuticals for targeted cancer therapy has led to an increased demand of ¹⁷⁷Lu-radionuclides all over the world. Since most of the clinically established targeted cancer therapies involve receptor targeting peptides, enzyme inhibitors or antibodies, the use of high specific activity ¹⁷⁷Lu is necessary to prepare ¹⁷⁷Lu complexes in high molar activity to obtain maximum efficacy of treatment. Therefore, there is an immense interest in the production of clinical grade no carrier added (NCA) ¹⁷⁷Lu globally. While carrier added ¹⁷⁷Lu can be produced by the neutron activation of an enriched ¹⁷⁶Lu target, NCA¹⁷⁷Lu is produced by neutron activation of an enriched ¹⁷⁶Yb target via the ¹⁷⁶Yb (n, γβ) ¹⁷⁷Lu reaction. The present work describes a semi-automated extraction chromatography-based modular separation system, which can be conveniently adopted for rapid isolation of medical grade NCA ¹⁷⁷Lu from the neutron irradiated enriched ¹⁷⁶Yb target. The separation module is based on multistage extraction chromatography using LN2 and DGA resins (3 stage each). Herein, we demonstrate effective utilization of this system to separate ¹⁷⁷Lu from the irradiated enriched ¹⁷⁶Yb target (+96.4%, 50–150 mg). The process could be completed within a short period of 4–5 h with overall 70–74% (26.6–74.0 GBq) ¹⁷⁷Lu recovery. The HPGe and ICP-AES analysis results for a typical batch indicated Yb impurity below 0.1% in isolated ¹⁷⁷Lu. The ¹⁷⁷Lu specific activity obtained was ∼1.6 GBq mg⁻¹ of lutetium. The NCA ¹⁷⁷LuCl₃ obtained by this route qualified all the necessary quality control tests for human use. To demonstrate the clinical utility, the NCA ¹⁷⁷LuCl₃ activity was used for the preparation of patient doses each of ¹⁷⁷Lu-DOTA-TATE (7.4 GBq) and ¹⁷⁷Lu-PSMA-617 (7.4 GBq). The 24 h post-therapy SPECT scan of the two cancer patients injected with the respective ¹⁷⁷Lu-radiopharmaceuticals (5.5–7.4 GBq) were in concordance with the corresponding ⁶⁸Ga-PET scans. The PLC based semi-automated separation system reported herein demonstrates the feasibility of NCA ¹⁷⁷LuCl₃ production in a short span of time, which can be effectively implemented at the commercial scale for formulation of clinical patient doses.