Research and challenges of radiopharmaceuticals in the treatment of bone diseases
10.13491/j.issn.1004-714X.2025.06.023
- VernacularTitle:放射性药物在骨疾病治疗中的研究与挑战
- Author:
Qingyu YAN
1
;
Zenghao WANG
2
;
Peng WANG
3
;
Luxu YIN
4
Author Information
1. The First Affiliated Hospital of Shandong First Medical University, Jinan 250100, China;Shandong First MedicalUniversity (Shandong Academy of Medical Sciences) School of Preventive Medicine (Institute of Radiological Medicine), Jinan 250117,China.
2. Shandong First MedicalUniversity (Shandong Academy of Medical Sciences) School of Preventive Medicine (Institute of Radiological Medicine), Jinan 250117,China.
3. The First Affiliated Hospital of Shandong First Medical University, Jinan 250100, China.
4. Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan 250100, China.
- Publication Type:ReviewArticles
- Keywords:
Radiopharmaceutical;
Bone metastatic cancer;
Multimodal treatment;
bone-targeting ligands ethylenediaminetetramethylenephosphonic acid/hydroxyethylidene diphosphonate
- From:
Chinese Journal of Radiological Health
2025;34(6):924-929
- CountryChina
- Language:Chinese
-
Abstract:
Both primary (e.g. osteosarcoma and Ewing sarcoma) and secondary (e.g. metastatic) bone cancers cause severe health problems and can lead to death. In recent years, radiopharmaceuticals have shown significant potential in the treatment of refractory bone diseases due to their unique targeting properties and low toxicity. Radiopharmaceutical therapy for bone cancer utilizes bone-seeking radiopharmaceuticals that target lesions through the high affinity of ethylenediaminetetramethylenephosphonic acid (EDTMP) ligand for bone hydroxyapatite. Traditional therapeutic agents such as 89Sr and 153Sm-EDTMP, administered via intravenous injection, accumulate in bone metastases and release beta rays to kill tumor cells. These agents can relieve pain and inhibit bone destruction; however, they have limited ability to shrink tumor volume or slow tumor growth (tumor volume reduction rate < 30%). Furthermore, these agents may cause systemic side effects, and existing evidence does not support their effectiveness in prolonging survival. The development of palliative bone pain therapies based on novel radiopharmaceuticals may overcome these limitations and improve the quality of life for patients during their remaining lifespan. Researchers have investigated the combination of various beta- and alpha-emitters with novel radionuclide carrier systems, significantly enhancing treatment precision in bone tumor models. For instance, 177Lu-EDTMP (beta ray 0.497 MeV, half-life 6.7 days) enabled 66% of patients to completely discontinue analgesics by the twelfth week. 186Re- and 188Re-hydroxyethylidene diphosphonate, by targeting hydroxyapatite, achieved a pain relief rate of up to 90% and significantly prolonged median survival. These agents caused only reversible hematological toxicity, with no Grade III/IV bone marrow suppression events, and significantly reduced tumor volume. Additionally, the alpha nuclide 223RaCl2 induces DNA breaks in tumor cells and inhibits osteoblast-osteoclast imbalance. When combined with best supportive care, it can extend overall survival by 3.6 months (14.9 months vs. 11.3 months), reduce the risk of death by 30%, and lead to significant tumor volume reduction. However, bone marrow toxicity management, cost-effectiveness balance, and the design of multimodal combination regimens remain key challenges.
