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Background  For almost a decade, terbium radioisotopes have been explored for their potential theragnostic application in nuclear medicine:  152 Tb and  155 Tb are the radioisotopes identified for PET or SPECT imaging, while  149 Tb and  161 Tb have suitable decay characteristics for α- and combined β − /Auger-e − -therapy, respectively. In the present study, the application of  152 Tb, 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.  152 Tb was employed for labeling PSMA-617, and the radioligand was extensively investigated in vitro to demonstrate similar characteristics to its  177 Lu-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,  152 Tb 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  68 Ga-PSMA-11 PET/CT acquired 45 min p.i.    Conclusions  The results of this study demonstrate the successful preparation and preclinical testing of  152 Tb-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  161 Tb, which has promising decay characteristics for an effective treatment of mCRPC patients.    Electronic supplementary material  The online version of this article (10.1186/s13550-019-0538-1) contains supplementary material, which is available to authorized users.

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