Optimisation of the manufacturing of the active substance PSMA-D4 for the synthesis of radiopharmaceuticals for targeted radiotherapy of metastatic prostate cancer

It is planned to optimise the chemical structure of a new PSMA membrane antigen inhibitor, the PSMA-D4 molecule, towards improving its metabolic stability and pharmacokinetics, as well as its safety. Based on in vitro (stability, specificity and binding strength to PSMA) and in vivo (pharmacokinetics, metabolic stability) studies, the PSMA-D4 enantiomer with the most favourable biological properties will be selected, followed by a process to optimise the manufacturing method, taking into account the highest synthesis yield and purity of the final product. The synthesis process will be carried out on a solid phase, and optimisation will include the phase, type of amino acid coupling agent, amino acid protecting groups, temperature, stoichiometry and reaction times. The ultimate goal of the project is to obtain the active substance PSMA-D4 according to GMP requirements, which meets several requirements for the manufacture of pharmaceutical substances. As part of the work plan, a specification of the active substance will be established, and validation of the relevant quality attributes and process parameters will be performed. The confirmation that the GMP standard is met will be a GIF authorisation for the manufacture of PSMA-D4 as API.