Preclinical investigations and first-in-human application of 152Tb-PSMA-617 for PET/CT imaging of prostate cancer

Cristina Mueller*, Aviral Singh, Christoph A. Umbricht, Harshad R. Kulkarni, Karl Johnston, Martina Bensova, Stefan Senftleben, Dirk Mueller, Christiaan Vermeulen, Roger Schibli, Ulli Koester, Nicholas P. van der Meulen, Richard P. Baum

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BackgroundFor almost a decade, terbium radioisotopes have been explored for their potential theragnostic application in nuclear medicine: Tb-152 and Tb-155 are the radioisotopes identified for PET or SPECT imaging, while Tb-149 and Tb-161 have suitable decay characteristics for alpha- and combined beta(-)/Auger-e(-)-therapy, respectively. In the present study, the application of Tb-152, in combination with PSMA-617 for imaging of prostate-specific membrane antigen (PSMA)-positive prostate cancer, was demonstrated in a preclinical setting and in a patient with metastatic castration-resistant prostate cancer (mCRPC).Results(152)Tb was produced at the ISOLDE facility at CERN/Geneva, Switzerland, by spallation, followed by on-line mass separation. The chemical separation was performed at Paul Scherrer Institute using chromatographic methods, as previously reported. Tb-152 was employed for labeling PSMA-617, and the radioligand was extensively investigated in vitro to demonstrate similar characteristics to its Lu-177-labeled counterpart. Preclinical PET/CT imaging studies performed with mice enabled visualization of PSMA-positive PC-3 PIP tumors, while uptake in PSMA-negative PC-3 flu tumors were absent. Based on these promising preclinical results, Tb-152 was shipped to Zentralklinik Bad Berka, Germany, where it was used for labeling of PSMA-617, enabling PET imaging of a patient with mCRPC. PET/CT scans were performed over a period of 25h post injection (p.i.) of the radioligand (140MBq). The images were of diagnostic quality, particularly those acquired at later time points, and enabled the detection of the same metastatic lesions and of local recurrent tumor as previously detected by Ga-68-PSMA-11 PET/CT acquired 45min p.i.ConclusionsThe results of this study demonstrate the successful preparation and preclinical testing of Tb-152-PSMA-617 and its first application in a patient with mCRPC. This work could pave the way towards clinical application of other Tb radionuclides in the near future, most importantly Tb-161, which has promising decay characteristics for an effective treatment of mCRPC patients.

Original languageEnglish
Article number68
Number of pages10
JournalEJNMMI Research
Volume9
DOIs
Publication statusPublished - 25 Jul 2019

Keywords

  • Tb-152
  • Terbium
  • PSMA-617
  • PET
  • CT imaging
  • Theragnostics
  • Prostate cancer
  • IN-VIVO
  • THERAPY
  • TB-161
  • LU-177
  • RADIONUCLIDES

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