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.