These side effects should be addressed before 225Ac-PRLT can be considered for earlier lines of treatment and not only for compassionate use. Therefore, the aim of LutADose is to increase the clinical applicability of tumour and organ dosimetry during 177Lu/225Ac-PRLT to allow individualized treatment schemes and move away from a ‘one fits all’ approach.
This includes improved quantitative 177Lu/225Ac-SPECT imaging during therapy to better estimate the pharmacokinetics (PK) of 177Lu/225Ac-PSMA ligands in tumours and organs at risk (OAR). For patients receiving 225Ac-PRLT as adjuvant therapy to 177Lu-PRLT, we will use 177Lu-PSMA PK information from the final 177Lu-PRLT cycle to better predict the absorbed dose of the subsequent 225Ac-PRLT cycle.
In addition, we will revisit the relative biological effectiveness (RBE) of 225Ac-PRLT vs 177Lu-PRLT for the salivary glands to better predict differences in radiotoxic effects between 225Ac-PRLT and 177Lu-PRLT. Meanwhile, small scale dosimetry will be considered for 225Ac-PRLT to better estimate the absorbed dose to OAR. Finally, we will evaluate the impact of the recoil daughter effect (RDE) for 225Ac-PRLT and the potential renal toxicity caused by redistribution of free 213Bi. As a result, we will increase the clinical applicability of image guided dosimetry during 177Lu/225Ac-PRLT such that therapeutic doses can be tailored for each patient individually to achieve a better risk–benefit balance and improved efficacy.