Evaluation of safety and dosimetry of 177Lu DOTA-ZOL for therapy of bone metastases.

Palliative treatment of bone metastasis using radiolabelled bisphosphonates is a well-known concept proven to be safe and effective. A new therapeutic radiopharmaceutical for bone metastasis is 177Lu-DOTA-Zoledronic acid (177Lu-DOTA-ZOL). In this study, safety and dosimetry of a single therapeutic dose of 177Lu DOTA-ZOL were evaluated based on a series of SPECT/CT images and blood samples. Methods: Nine patients with exclusive bone metastases from metastatic castration-resistant prostate cancer (mCRPC) (70.8±8.4 y) and progression under conventional therapies participated in this prospective study. After receiving 5780±329 MBq 177Lu-DOTA-ZOL, patients underwent 3D whole-body SPECT/CT imaging and venous blood sampling over seven days. Dosimetric evaluation was performed for main organs and tumor lesions. Safety was assessed by blood biomarkers. Results:177Lu-DOTA-ZOL showed fast uptake and high retention in bone lesions and fast clearance from the blood stream in all patients. The average retention in tumor lesions was 0.02 %IA/g at 6 h post-injection (p.i.) and approximately 0.01 %IA/g at 170 h p.i. In this cohort, the average absorbed doses in bone tumor lesions, kidneys, red bone marrow, and bone surfaces were 4.21, 0.17, 0.36, and 1.19 Gy/GBq, respectively. The red marrow was found to be the dose-limiting organ for all patients. A median maximum tolerated injected activity of 6.0 GBq may exceed the defined threshold of 2 Gy for the red bone marrow in individual patients (4/8). Conclusion: In conclusion, 177Lu-DOTA-ZOL is safe and has a favorable therapeutic index compared to other radiopharmaceuticals used in the treatment of osteoblastic bone metastases. Personalized dosimetry, however, should be considered to avoid severe hematotoxicity for individual patients.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2021 Jan 08 [Epub ahead of print]

Rene Fernandez, Elisabeth Eppard, Wencke Lehnert, Luis David Jimenez-Franco, Cristian Soza-Ried, Matias Ceballos, Jessica Ribbeck, Andreas Kluge, Frank Roesch, Marian Meckel, Konstantin Zhernosekov, Vasko Kramer, Horacio Amaral

Center for Nuclear Medicine & PET/CT Positronmed., Positronpharma SA, Chile., ABX-CRO, Germany., Institute of Nuclear Chemistry, Johannes Gutenberg-University, Germany., Isotope Technologies Garching GmbH, Germany.