Kramer Carsten S, Zhang Jingjing, Baum Richard P
CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany.
Department of Diagnostic Radiology, Clinical Imaging Research Centre, National University of Singapore, Singapore, Singapore.
Front Med (Lausanne). 2024 Oct 9;11:1462234. doi: 10.3389/fmed.2024.1462234. eCollection 2024.
Herein we report, for the first time, the therapeutic response of a prostate cancer patient with the thiamine antagonist benfo-oxythiamine (B-OT) added to prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT). The patient was initially diagnosed as pT3b pN0 (0/7) M0 L0 V0 R0 G3, Gleason score 5 + 5 = 10, with an initial prostate-specific antigen (PSA) level of 4.05 ng/ml. Shortly after radical prostatectomy, Ga-PSMA positron emission tomography/computed tomography (PET/CT) revealed PSMA-positive lymph node metastases. Despite treatment with androgen deprivation therapy, external beam radiation therapy, palliative chemotherapy, and five cycles of PRLT (Lu-PRLT or TANDEM-PRLT, respectively), the patient experienced progression in PSA levels as well as in PSMA PET/CT. Due to the intense PSMA expression, Lu-PRLT with Lu-PSMA-I&T was resumed for another 4 cycles (cycles 6th to 9th) and the patient was additionally treated with the thiamine antagonist benfo-oxythiamine. It was hypothesized that B-OT acts as a radiosensitizer by interfering with the repair of damaged DNA. B-OT-PRLT was well-tolerated and no substantial changes in laboratory results were observed. Additionally, the patient reported significant improvement in clinical symptoms. Post-treatment Lu-PSMA single-photon computed tomography (SPECT)/CT after the 7th cycle (and after 2 cycles of B-OT-PRLT) revealed regression of metastases compared to the post-treatment SPECT/CT after the 6th cycle. Before the 8th cycle, PSMA PET/CT showed a mixed response following prior uncontrollable cancer progression. Moreover, the PSA level showed a significant decline after one cycle of B-OT-PRLT. Although the patient had experienced massive progression before the first cycle of B-OT-PRLT, he survived for an additional 12 months. This case supports the hypothesis that B-OT-PRLT could overcome radiation resistance in prostate cancer patients who do not initially respond to Lu- or Ac-PRLT.
在此，我们首次报告了一名前列腺癌患者在接受前列腺特异性膜抗原（PSMA）靶向放射性配体治疗（PRLT）时添加硫胺拮抗剂苯甲酰氧硫胺（B-OT）后的治疗反应。该患者最初被诊断为pT3b pN0（0/7）M0 L0 V0 R0 G3，Gleason评分5 + 5 = 10，初始前列腺特异性抗原（PSA）水平为4.05 ng/ml。根治性前列腺切除术后不久，镓-PSMA正电子发射断层扫描/计算机断层扫描（PET/CT）显示PSMA阳性淋巴结转移。尽管接受了雄激素剥夺治疗、外照射放疗、姑息化疗以及五个周期的PRLT（分别为镥-PRLT或串联-PRLT），患者的PSA水平以及PSMA PET/CT仍出现进展。由于PSMA表达强烈，再次进行了四个周期（第6至9周期）的镥-PSMA-1&T的镥-PRLT治疗，并且患者额外接受了硫胺拮抗剂苯甲酰氧硫胺治疗。据推测，B-OT通过干扰受损DNA的修复而起到放射增敏剂的作用。B-OT-PRLT耐受性良好，未观察到实验室结果有实质性变化。此外，患者报告临床症状有显著改善。第7周期（以及两个周期的B-OT-PRLT后）治疗后的镥-PSMA单光子计算机断层扫描（SPECT）/CT显示，与第6周期治疗后的SPECT/CT相比，转移灶有所消退。在第8周期之前，PSMA PET/CT显示在先前无法控制的癌症进展后出现混合反应。此外，PSA水平在一个周期的B-OT-PRLT后显著下降。尽管该患者在第一个周期的B-OT-PRLT之前经历了大量进展，但他又存活了12个月。该病例支持了这样一种假设，即B-OT-PRLT可以克服最初对镥-或锕-PRLT无反应的前列腺癌患者的放射抗性。
