Skip to main content

CASE REPORT article

Front. Med.
Sec. Nuclear Medicine
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1462234

Extraordinary therapeutic effect of PSMA radioligand therapy in treatment-refractory progressive metastatic prostate cancer with the transketolase inhibitor benfo-oxythiamine as a radiosensitizer -A Case Report

Provisionally accepted
Carsten S. Kramer Carsten S. Kramer 1Jingjing Zhang Jingjing Zhang 2Richard P. Baum Richard P. Baum 1*
  • 1 CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany
  • 2 Department of Diagnostic Radiology & Clinical Imaging Research Centre, National University of Singapore, Singapore, Singapore

The final, formatted version of the article will be published soon.

    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, 68 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 ( 177 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, 177 Lu-PRLT with 177 Lu-PSMA-I&T was resumed for another 4 cycles (cycles 6 th to 9 th ) 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 177 Lu-PSMA single-photon computed tomography (SPECT)/CT after the 7 th cycle (and after 2 cycles of B-OT-PRLT) revealed regression of metastases compared to the post-treatment SPECT/CT after the 6 th cycle. Before the 8 th 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 177 Lu-or 225 Ac-PRLT.

    Keywords: radiosensitizer, Transketolase, TKTL1, thiamine antagonist, benfo-oxythiamine, 177 Lu-PSMA, metastatic castration-resistant prostate cancer, case report

    Received: 09 Jul 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Kramer, Zhang and Baum. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Richard P. Baum, CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.