Development and validation of a quality control system for pharmaceutical development and production of targeted alpha therapies

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Next-generation cancer treatments using radiopharmaceuticals have the potential to transform cancer treatment methodology. Targeted Alpha Therapy (TAT), in particular, is an extremely promising, emerging cancer treatment, in which alpha radiation is targeted to cancerous cells, selectively killing both localised tumours and delocalised cancers (including metastatic cancers and leukaemia). It utilises the exceptionally high energy deposition of the alpha emitters, combined with the high so-called Linear Energy Transfer (LET), directly generating double-stranded DNA breakages. An initial experimental investigation of TAT demonstrated the power of such a treatment through PSMA targeting of a castration-resistant prostate cancer. The patient had wide-spread metastases, but after radiopharmaceutical treatment with Ac-225 labelled PSMA-617, the patient entered remission [Kratochwil, et al., J.Nucl.Med. 57(2016)1941].The present project offers to capitalise on the achievements of a previous STFC Follow-on-Funding project (ST/T003162/1), taking a developed device from the stage of critical functionality tests to the development and validation of a quality control (QC) system for radiopharmaceutical alpha therapy development based on the device, a microfluidic alpha-particle sensor (MAS). In the present project, this will be embedded in a fluidic QC system developed for utilisation in both isotope production and subsequent radiopharmaceutical QC. The critical functions of the technology (sensor and fluidic) have recently been demonstrated analytically and experimentally (ST/T003162/1) as proof-of-concept up to a current level of TRL 3 (analytical and experimental critical function or characteristic proof-of-concept).The overarching objectives are: (O.1) to develop proof-of-concept QC processes for alpha treatment development and production, with an industry partner (LabLogic), in line with the requirements of the radiopharmaceutical industry; (O.2) to determine further technology specifications required to meet these requirements; (O.3) to test a range of implementation options to meet these requirements to a stage where a complete device - in principle - has been developed, taking into account the advancements required for QC; and (O.4) to carry out a validation of the combined technology and its potential for radiopharmaceutical QC in a controlled laboratory environment (TRL 4: technology basic validation in a laboratory environment, EXACT, Southampton) and with an established medical isotope producer (TRL 5: technology basic validation in a relevant environment, TRIUMF, Canada). As a key objective of the project (O.5), the partnerships with TRIUMF and LabLogic will be strengthened and utilised to advance both IP development and market development for the device and associated QC processes, as well as to generate new UK capacity for future TAT developments.