Project

PROGNOSTICS: PeRsOnalized theraGNOstics of metaStaTIC proState cancer

Short Summary

The project objective is to evaluate the efficacy and safety of a novel radioligand (161Tb-SibuDAB) developed at PSI and to compare it with standard radioligand therapy (RLT) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC) in an early clinical study. As we hypothesize that circulating cancer cells (CTC) and tumor cell clusters are one of the main causes of failure after standard RLT, we will evaluate the presence of CTC and tumor cell clusters as an efficacy and predictive marker.

Goals

In the current project, we want to assess the safety and tolerability the novel PSMA radioligand 161Tb-SibuDAB. Terbium-161 (161Tb) emits β-minus particles and, in addition, a substantial amount of conversion and Auger electrons. These electrons have a tissue range of a few nanometers, resulting in a 2-4-fold higher radiation dose to CTC and tumor cell clusters. Furthermore, we want to assess a potential correlation between CTC/clusters and response to standard RLT. The team at PSI is responsible for the production of 161Tb-SibuDAB (including the radionuclide), the team at the ETH Zurich is analyzing the blood samples of patients for the presence of CTC and tumor cell clusters with its technique and the team at USB will conduct the clinical study.

Significance

The delivered of higher radiation dose to macroscopic tumors as well as micrometastases will improve the therapeutic outcome of patients suffering from mCRPC that currently fail treatment. In addition, the project will help to better understand the correlation between the amount for CTC and cancer cell clusters and tumor response.

Background

RLT emerged as an effective means for the treatment of patients with prostate-specific membrane antigen (PSMA)-positive mCRPC. Despite the success of this therapy, 1/3 of the patients do not or only temporarily respond to treatment with β-minus particle emitting radionuclide only such as Lutetium-177. It is hypothesized that the insufficient radiation dose delivery to macroscopic tumors and to microscopic metastases with currently used 177Lu-based PSMA radioligands is the reason for the treatment failure in these patients.