Damiana Tyrillshall S T, van den Brink Lilian, de Kreij-de Bruin Lisette W, Stuurman Debra C, de Ridder Corrina M A, Dalm Simone U
Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Experimental Urology, Erasmus Medical Center, Rotterdam, The Netherlands.
EJNMMI Res. 2025 Aug 1;15(1):98. doi: 10.1186/s13550-025-01302-x.
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 [Lu]Lu-NeoB uptake in PC-3 xenografts, but this was not GRPR mediated. DXR pre-treatment did not alter [Lu]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.
靶向胃泌素释放肽受体（GRPR）的放射性示踪剂已在临床前研究中取得了有前景的结果。适合这种治疗的患者可能之前接受过包括化疗在内的其他抗癌药物治疗。已知化疗会改变癌细胞的基因表达和放射敏感性，这可能会影响GRPR的表达以及对放射性核素治疗的反应。我们研究了两种常用化疗药物阿霉素（DXR）和多西他赛（DTX）对前列腺癌（PCa）和乳腺癌（BC）细胞中GRPR表达、GRPR放射性示踪剂摄取以及对外照射放疗（EBRT）和靶向放射性核素治疗反应的影响。此外，在化疗治疗后，使用SPECT/CT评估了靶向GRPR的放射性示踪剂“NeoB”在携带PC-3和T47D异种移植瘤的小鼠体内的摄取情况。
DTX显著降低了PC-3细胞在体外的GRPR表达、放射性示踪剂摄取和放射敏感性。DXR预处理的T47D细胞表现出GRPR表达和放射性示踪剂摄取增加，并且对EBRT的敏感性降低。在体内，DTX预处理增加了PC-3异种移植瘤中[Lu]Lu-NeoB的摄取，但这不是由GRPR介导的。DXR预处理未改变T47D异种移植瘤中[Lu]Lu-NeoB的摄取，但观察到GRPR mRNA表达增加。
我们的数据表明，化疗在体外改变了与GRPR介导的放射性核素治疗在PCa和BC细胞中成功相关的机制。这些发现在体内不太明显，需要进一步研究来阐明这一点。
