Background: For almost a decade, terbium radioisotopes have been explored for their potential theragnostic application in nuclear medicine: ¹⁵²Tb and ¹⁵⁵Tb are the radioisotopes identified for PET or SPECT imaging, while ¹⁴⁹Tb and ¹⁶¹Tb have suitable decay characteristics for α- and combined β^-/Auger-e^--therapy, respectively. In the present study, the application of ¹⁵²Tb, 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: ¹⁵²Tb 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. ¹⁵²Tb was employed for labeling PSMA-617, and the radioligand was extensively investigated in vitro to demonstrate similar characteristics to its ¹⁷⁷Lu-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, ¹⁵²Tb 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 25 h post injection (p.i.) of the radioligand (140 MBq). 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 ⁶⁸Ga-PSMA-11 PET/CT acquired 45 min p.i.
Conclusions: The results of this study demonstrate the successful preparation and preclinical testing of ¹⁵²Tb-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 ¹⁶¹Tb, which has promising decay characteristics for an effective treatment of mCRPC patients.