TY - JOUR
T1 - Preclinical investigations and first-in-human application of 152Tb-PSMA-617 for PET/CT imaging of prostate cancer
AU - Mueller, Cristina
AU - Singh, Aviral
AU - Umbricht, Christoph A.
AU - Kulkarni, Harshad R.
AU - Johnston, Karl
AU - Bensova, Martina
AU - Senftleben, Stefan
AU - Mueller, Dirk
AU - Vermeulen, Christiaan
AU - Schibli, Roger
AU - Koester, Ulli
AU - van der Meulen, Nicholas P.
AU - Baum, Richard P.
N1 - Funding Information:
The authors thank Raffaella Schmid and Susan Cohrs for assistance in the study, as well as the people responsible for radiation safety and radioactive transport at the Center for Radiopharmaceutical Sciences at PSI and CERN. The authors are grateful to Walter Hirzel, Alexander Sommerhalder and Muhamet Djelili (Radionuclide Production and Maintenance Group at CRS, PSI) for technical assistance. The authors thank the ISOLDE RILIS team for efficient Dy ionization and the ISOLTRAP-MR-TOF-MS team for beam characterization. Furthermore, the authors express their gratitude to the nursing staff as well as to the nuclear medicine technologists of the Theranostics Center for Molecular Radiotherapy and Precision Oncology for patient management at ZBB.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/7/25
Y1 - 2019/7/25
N2 - 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.
AB - 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.
KW - Tb-152
KW - Terbium
KW - PSMA-617
KW - PET
KW - CT imaging
KW - Theragnostics
KW - Prostate cancer
KW - IN-VIVO
KW - THERAPY
KW - TB-161
KW - LU-177
KW - RADIONUCLIDES
U2 - 10.1186/s13550-019-0538-1
DO - 10.1186/s13550-019-0538-1
M3 - Article
C2 - 31346796
SN - 2191-219X
VL - 9
JO - EJNMMI Research
JF - EJNMMI Research
IS - 1
M1 - 68
ER -