Chemotherapy alters radiosensitivity and GRPR expression of prostate and breast cancer cells

Gastrin releasing peptide receptor (GRPR)-targeting radiotracers have been studied (pre)-clinically with promising results. Patients eligible for this treatment are likely to have undergone prior treatments with other anti-cancer agents, including chemotherapy. Chemotherapies are known to alter cancer cell's gene expression and radiosensitivity, potentially impacting GRPR expression and the response to radionuclide therapy. We studied the effect of two commonly applied chemotherapies, doxorubicin (DXR) and docetaxel (DTX), on GRPR expression, GRPR radiotracer uptake, and response to external beam radiation therapy (EBRT) and targeted radionuclide treatment, in prostate cancer (PCa) and breast cancer (BC) cells. Additionally, in-vivo uptake of the GRPR-targeting radiotracer "NeoB" in PC-3 and T47D xenograft-bearing mice was assessed using SPECT/CT following chemotherapy treatment.

DTX significantly decreased GRPR expression, radiotracer uptake, and radiosensitivity of PC-3 cells in-vitro. DXR pre-treated T47D cells demonstrated an increased GRPR expression and radiotracer uptake, and were less sensitive to EBRT. In-vivo, DTX pre-treatment increased [¹⁷⁷Lu]Lu-NeoB uptake in PC-3 xenografts, but this was not GRPR mediated. DXR pre-treatment did not alter [¹⁷⁷Lu]Lu-NeoB uptake in T47D xenografts, but an increase in GRPR mRNA expression was observed.

Our data demonstrated that chemotherapy alters mechanisms relevant for the success of GRPR-mediated radionuclide therapy in PCa and BC cells in-vitro. These finding were less prominent in-vivo and additional studies are needed to unravel this.