Safety and Efficacy of 68Ga- or 177Lu-Labeled DOTA-IBA as a Novel Theranostic Radiopharmaceutical for Bone Metastases

Abstract

Purpose We designed and synthesized a novel theranostic bisphosphonate radiopharmaceutical (68Ga- or 177Lu-labeled DOTA-ibandronic acid [68Ga/177Lu-DOTA-IBA]) for bone metastasis. In this study, the dosimetry, safety, and efficacy of 68Ga/177Lu-DOTA-IBA as a theranostic radiopharmaceutical for bone metastases were evaluated in patients with malignancy based on 68Ga- and 177Lu-DOTA-IBA images, blood samples, and dosimetric analysis. Patients and Methods Eighteen patients with bone metastasis and progression under conventional therapies were included in this study. Baseline 99mTc-MDP SPECT and 68Ga-DOTA-IBA PET/CT were performed for comparative purposes within 3 days. After receiving 891.5 ± 301.3 MBq 177Lu-DOTA-IBA, serial 177Lu-DOTA-IBA SPECT bone scan was performed over 14 days. Dosimetric evaluation was performed for main organs and tumor lesions. Safety was assessed by blood biomarkers. Karnofsky Performance Status, pain score, and follow-up 68Ga-DOTA-IBA PET/CT were performed for response evaluation. Results Baseline 68Ga-DOTA-IBA PET demonstrated a higher efficacy for detecting bone metastases compared with 99mTc-MDP SPECT. The time-activity curves showed fast uptake and high retention of 177Lu-DOTA-IBA in bone metastases (24 hours: 9.43 ± 2.75 %IA; 14 days: 5.45 ± 2.52 %IA). Liver, kidneys, and red marrow time-activity curves revealed a low uptake and fast clearance. The radiation-absorbed dose in bone metastasis lesions (6.40 ± 2.13 Gy/GBq) was significantly higher than that in red marrow (0.47 ± 0.19 Gy/GBq), kidneys (0.56 ± 0.19 Gy/GBq), or liver (0.28 ± 0.07 Gy/GBq), with all P’s < 0.001. Compared with baseline level, only one patient developed new grade 1 leukopenia (toxicity rate, 6%). The 177Lu-DOTA-IBA therapy had no statistically significant effect on bone marrow hematopoietic function, liver function, and kidney function at any follow-up visit. Bone pain palliation was achieved in 82% (14/17) of patients. The 8-week follow-up 68Ga-DOTA-IBA PET/CT demonstrated partial response in 3 patients, disease progression in 1 patient, and stable disease in 14 patients. Conclusions 68Ga/177Lu-DOTA-IBA provides a set of potential theranostic radiopharmaceuticals and may have a good prospect for the management of bone metastasis.