Abstract
Palliative treatment of bone metastasis using radiolabeled 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, the safety and dosimetry of a single therapeutic dose of 177Lu-DOTA-ZOL were evaluated on the basis of 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 5,780 ± 329 MBq 177Lu-DOTA-ZOL, patients underwent 3-dimensional whole-body SPECT/CT imaging and venous blood sampling over 7 d. 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 bloodstream in all patients. The average retention in tumor lesions was 0.02% injected activity per gram at 6 h after injection and approximately 0.01% at 170 h after injection. 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:177Lu-DOTA-ZOL is safe and has a favorable therapeutic index compared with other radiopharmaceuticals used in the treatment of osteoblastic bone metastases. Personalized dosimetry, however, should be considered to avoid severe hematotoxicity for individual patients.
Highlights
5,780 6 329 MBq of 177Lu-DOTA-ZOL were administered over 6–10 s followed by a saline flush
Nine male patients (70.8 6 8.4 y) with metastatic castrationresistant prostate cancer with exclusive bone metastases were enrolled for evaluation of safety and dosimetry of a therapeutic dose of 5,780 6 329 MBq of 177Lu-DOTA-ZOL
One patient was retrospectively excluded from the dosimetry analysis because of strong motion artifacts in the SPECT data
Summary
Study Design and Patients Study approval was obtained from the regional ethics committee board (CEC-SSM-Oriente, permit 20170829). Activity values were retrieved from the SPECT images using a threshold-based segmentation algorithm for the kidneys (left and right), urinary bladder content, skeleton (excluding tumor regions), and total body. Because the segmented volumes of interest for the total body and the skeleton did not include the legs, the obtained activity values for these organs were scaled by a factor of 1.506 (1.506 5 1/0.664), representing the legs with 33.6% of the total bone mass [21]. The time–activity curves for source organs and tumor lesions were determined by the activity values and acquisition times of the SPECT scans. Organ and tumor lesion time–activity curves were fitted to a sum of exponential functions, which were integrated from time 0 to infinity to obtain cumulated activity values.
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