LUTADOSE

LutADose: Personalized dosimetry to improve the clinical outcome of prostate cancer patients treated with 177Lu/225Ac-PSMA targeted therapies.

Project objectives and goals: 

Prostate cancer is the second most frequent malignancy worldwide with metastatic castration-resistant prostate cancer (mCRPC) being very difficult to treat. A possible treatment of mCRPC is PSMA (prostate-specific membrane antigen) radioligand therapy (PRLT) to deliver a targeted high dose of ionizing radiation directly to tumour cells. However, current treatment schemes for ¹⁷⁷Lu(Beta)-PRLT use fixed therapeutic schemes, resulting in a conservative tendency to undertreat patients and sacrificing efficacy for safety. As a result, complete response is still uncommon with about 30% of patients not responding to treatment. Meanwhile, ²²⁵Ac(Alpha)-PRLT has emerged as adjuvant therapy to improve efficacy and overcome the potential radio resistance to ¹⁷⁷Lu-PRLT. However, ²²⁵Ac-PRLT can induce significant side effects such as salivary radiotoxicity, which has led patients to request treatment discontinuation.

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.

Project coordinator

Michel Koole, KU Leuven (KUL), Belgium

Project partners

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