Christiane Schuchardt1, Jingjing Zhang2,3, Harshad R Kulkarni4, Xiaoyuan Chen2,3,5, Dirk Müller6, Richard P Baum7. 1. Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; christiane.schuchardt@zentralklinik.de. 2. Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 3. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 4. Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany. 5. Departments of Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, Singapore. 6. University Hospital Ulm, Clinic for Nuclear Medicine, Ulm, Germany; and. 7. Curanosticum Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany.
Abstract
The objective of this study was to determine the safety, kinetics, and dosimetry of the 177Lu-labeled prostate-specific membrane antigen (PSMA) small molecules 177Lu-PSMA I&T and 177Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT). Methods: In total, 138 patients (mean age, 70 ± 9 y; age range, 46-90 y) with progressive mCRPC and PSMA expression verified by 68Ga-PSMA-11 PET/CT underwent PRLT. Fifty-one patients received 6.1 ± 1.0 GBq (range, 3.4-7.6 GBq) of 177Lu-PSMA I&T, and 87 patients received 6.5 ± 1.1 GBq (range, 3.5-9.0 GBq) of 177Lu-PSMA-617. Dosimetry was performed on all patients using an identical protocol. The mean absorbed doses were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 5.0, of the National Cancer Institute. Results: The whole-body half-lives were shorter for 177Lu-PSMA I&T (35 h) than for 177Lu-PSMA-617 (42 h). The mean whole-body dose of 177Lu-PSMA-617 was higher than that of 177Lu-PSMA I&T (0.04 vs. 0.03 Gy/GBq, P < 0.00001). Despite the longer half-life of 177Lu-PSMA-617, the renal dose was lower for 177Lu-PSMA-617 than for 177Lu-PSMA I&T (0.77 vs. 0.92 Gy/GBq, P = 0.0015). Both PSMA small molecules demonstrated a comparable dose to the parotid glands (0.5 Gy/GBq, P = 0.27). Among all normal organs, the lacrimal glands exhibited the highest mean absorbed doses, 5.1 and 3.7 Gy/GBq, for 177Lu-PSMA-617 and 177Lu-PSMA I&T, respectively. All tumor metastases exhibited a higher initial uptake when using 177Lu-PSMA I&T than when using 177Lu-PSMA-617, as well as a shorter tumor half-life (P < 0.00001). The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617 (5.8 vs. 5.9 Gy/GBq, P = 0.96). All patients tolerated the therapy without any acute adverse effects. After 177Lu-PSMA-617 and 177Lu-PSMA I&T, there was a small, statistically significant reduction in hemoglobin, leukocyte counts, and platelet counts that did not need any clinical intervention. No nephrotoxicity was observed after either 177Lu-PSMA I&T or 177Lu-PSMA-617 PRLT. Conclusion: Both 177Lu-PSMA I&T and 177Lu-PSMA-617 PRLT demonstrated favorable safety in mCRPC patients. The highest absorbed doses among healthy organs were in the lacrimal and parotid glands-not, however, resulting in any significant clinical sequel. 177Lu-PSMA-617 demonstrated a higher absorbed dose to the whole-body and lacrimal glands but a lower renal dose than did 177Lu-PSMA I&T. The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617. There was a large interpatient variability in the dosimetry parameters. Therefore, individual patient-based dosimetry seems favorable for personalized PRLT.
The objective of this study was to determine the safety, kinetics, and dosimetry of the 177Lu-labeled prostate-specific membrane antigen (PSMA) small molecules 177Lu-PSMA I&T and 177Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT). Methods: In total, 138 patients (mean age, 70 ± 9 y; age range, 46-90 y) with progressive mCRPC and PSMA expression verified by 68Ga-PSMA-11 PET/CT underwent PRLT. Fifty-one patients received 6.1 ± 1.0 GBq (range, 3.4-7.6 GBq) of 177Lu-PSMA I&T, and 87 patients received 6.5 ± 1.1 GBq (range, 3.5-9.0 GBq) of 177Lu-PSMA-617. Dosimetry was performed on all patients using an identical protocol. The mean absorbed doses were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 5.0, of the National Cancer Institute. Results: The whole-body half-lives were shorter for 177Lu-PSMA I&T (35 h) than for 177Lu-PSMA-617 (42 h). The mean whole-body dose of 177Lu-PSMA-617 was higher than that of 177Lu-PSMA I&T (0.04 vs. 0.03 Gy/GBq, P < 0.00001). Despite the longer half-life of 177Lu-PSMA-617, the renal dose was lower for 177Lu-PSMA-617 than for 177Lu-PSMA I&T (0.77 vs. 0.92 Gy/GBq, P = 0.0015). Both PSMA small molecules demonstrated a comparable dose to the parotid glands (0.5 Gy/GBq, P = 0.27). Among all normal organs, the lacrimal glands exhibited the highest mean absorbed doses, 5.1 and 3.7 Gy/GBq, for 177Lu-PSMA-617 and 177Lu-PSMA I&T, respectively. All tumor metastases exhibited a higher initial uptake when using 177Lu-PSMA I&T than when using 177Lu-PSMA-617, as well as a shorter tumor half-life (P < 0.00001). The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617 (5.8 vs. 5.9 Gy/GBq, P = 0.96). All patients tolerated the therapy without any acute adverse effects. After 177Lu-PSMA-617 and 177Lu-PSMA I&T, there was a small, statistically significant reduction in hemoglobin, leukocyte counts, and platelet counts that did not need any clinical intervention. No nephrotoxicity was observed after either 177Lu-PSMA I&T or 177Lu-PSMA-617 PRLT. Conclusion: Both 177Lu-PSMA I&T and 177Lu-PSMA-617 PRLT demonstrated favorable safety in mCRPC patients. The highest absorbed doses among healthy organs were in the lacrimal and parotid glands-not, however, resulting in any significant clinical sequel. 177Lu-PSMA-617 demonstrated a higher absorbed dose to the whole-body and lacrimal glands but a lower renal dose than did 177Lu-PSMA I&T. The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617. There was a large interpatient variability in the dosimetry parameters. Therefore, individual patient-based dosimetry seems favorable for personalized PRLT.
Authors: J A Siegel; S R Thomas; J B Stubbs; M G Stabin; M T Hays; K F Koral; J S Robertson; R W Howell; B W Wessels; D R Fisher; D A Weber; A B Brill Journal: J Nucl Med Date: 1999-02 Impact factor: 10.057
Authors: Andreas Delker; Wolfgang Peter Fendler; Clemens Kratochwil; Anika Brunegraf; Astrid Gosewisch; Franz Josef Gildehaus; Stefan Tritschler; Christian Georg Stief; Klaus Kopka; Uwe Haberkorn; Peter Bartenstein; Guido Böning Journal: Eur J Nucl Med Mol Imaging Date: 2015-08-29 Impact factor: 9.236
Authors: Clemens Kratochwil; Frederik L Giesel; Karin Leotta; Matthias Eder; Torsten Hoppe-Tich; Hagop Youssoufian; Klaus Kopka; John W Babich; Uwe Haberkorn Journal: J Nucl Med Date: 2015-01-22 Impact factor: 10.057
Authors: Christiane Schuchardt; Harshad R Kulkarni; Vikas Prasad; Carolin Zachert; Dirk Müller; Richard P Baum Journal: Recent Results Cancer Res Date: 2013
Authors: John Violet; Price Jackson; Justin Ferdinandus; Shahneen Sandhu; Tim Akhurst; Amir Iravani; Grace Kong; Aravind Ravi Kumar; Sue Ping Thang; Peter Eu; Mark Scalzo; Declan Murphy; Scott Williams; Rodney J Hicks; Michael S Hofman Journal: J Nucl Med Date: 2018-10-05 Impact factor: 10.057
Authors: John Violet; Shahneen Sandhu; Amir Iravani; Justin Ferdinandus; Sue-Ping Thang; Grace Kong; Aravind Ravi Kumar; Tim Akhurst; David A Pattison; Alexis Beaulieu; Jennifer Mooi; Ben Tran; Christina Guo; Victor Kalff; Declan G Murphy; Price Jackson; Peter Eu; Mark Scalzo; Scott Williams; Rodney J Hicks; Michael S Hofman Journal: J Nucl Med Date: 2019-11-15 Impact factor: 11.082
Authors: Lena M Unterrainer; Leonie Beyer; Mathias J Zacherl; Franz J Gildehaus; Andrei Todica; Sophie C Kunte; Adrien Holzgreve; Gabriel T Sheikh; Annika Herlemann; Jozefina Casuscelli; Matthias Brendel; Nathalie L Albert; Vera Wenter; Nina-Sophie Schmidt-Hegemann; Wolfgang G Kunz; Clemens C Cyran; Jens Ricke; Christian G Stief; Peter Bartenstein; Harun Ilhan; Marcus Unterrainer Journal: Biomedicines Date: 2022-04-20
Authors: Wietske I Luining; Matthijs C F Cysouw; Dennie Meijer; N Harry Hendrikse; Ronald Boellaard; André N Vis; Daniela E Oprea-Lager Journal: Cancers (Basel) Date: 2022-02-24 Impact factor: 6.639
Authors: Ralph A Bundschuh; Rudolf A Werner; Philipp E Hartrampf; Franz-Xaver Weinzierl; Andreas K Buck; Steven P Rowe; Takahiro Higuchi; Anna Katharina Seitz; Hubert Kübler; Andreas Schirbel; Markus Essler Journal: Eur J Nucl Med Mol Imaging Date: 2022-03-04 Impact factor: 10.057
Authors: Philipp E Hartrampf; Anna Katharina Seitz; Andreas K Buck; Rudolf A Werner; Franz-Xaver Weinzierl; Sebastian E Serfling; Andreas Schirbel; Steven P Rowe; Hubert Kübler Journal: Eur J Nucl Med Mol Imaging Date: 2022-06-02 Impact factor: 10.057