The clinical diagnosis and treatment of malignant bone tumors are still major clinical challenges due to their high incidence are difficulty. Targeted therapies have become a critical approach to treat bone tumors. In recent years, radiopharmaceuticals have been used widely and have shown potent and efficient results in treating bone tumors, among which 32P and the labeled radiopharmaceuticals play an essential role. In this study, the 32P-labeled hydroxyapatite (HA) was prepared through chemical synthesis (32P-Hap) and physical adsorption (32P-doped-Hap). The in vitro stability of 32P-labeled HA was analyzed to assess the superiority of the new-found chemical synthesis. The radiolabeling yield and stability of chemical synthesis (97.6 ± 0.5%) were significantly improved compared with physical adsorption (92.7 ± 0.4%). Furthermore, the CT results corroborate that 32P-Hap (100 μCi) +DOX group has the highest tumor suppression rate and can effectively reduce bone destruction. The results corroborate the effectiveness of the chemical synthesis and validate the application of 32P-Hap in bone tumors. Therefore, 32P-Hap (100 μCi) + DOX may be an effective strategy for bone metastasis treatments.
Background Prostate cancer (PCa) ranks second in the incidence of all malignancies in male worldwide. The presence of multi-organ metastases and tumor heterogeneity often leads to unsatisfactory outcomes of conventional radiotherapy treatments. This study aimed to develop a novel folate-targeted nanohydroxyapatite (nHA) coupling to deliver adriamycin (Doxorubicin, DOX), 32P, and 99mTc simultaneously for the diagnosis and treatment of prostate-specific membrane antigen (PSMA) positive prostate cancer.Methods The spherical nHA was prepared by the biomimetic method and characterized. Folic acid (FA) was coupled to nHA with polyethylene glycol (PEG), and the grafting ratio of PEG-nHA and FA-PEG-nHA was determined by the thermogravimetric analysis (TGA) method. In addition, 32P, 99mTc, and DOX were loaded on nHA by physisorption. And the labeling rate and stability of radionuclides were measured by a γ-counter. The loading and release of DOX at different pH were determined by the dialysis method. Targeting of FA-PEG-nHA loaded with 99mTc was verified by in vivo SPECT imaging. In vitro anti-tumor effect of 32P/DOX-FA-PEG-nHA was assessed with apoptosis assay. The safety of the nano-drugs was verified by histopathological analysis.Results The SEM images showed that the synthesized nHA was spherical with uniform particle size (average diameter of about 100nm). The grafting ratio is about 10% for PEG and about 20% for FA. The drug loading and the delayed release of DOX at different pH confirmed its long-term therapeutic ability. The labeling of 32P and 99mTc was stable and the labeling rate was great. SPECT showed that FA-PEG-nHA showed well in vivo tumor targeting and less damage to normal tissues.Conclusion FA-targeted nHA loaded with 32P, 99mTc, and DOX may be a new diagnostic and therapeutic strategy for targeting PSMA-positive prostate cancer tumors, which may achieve better therapeutic results while circumventing the severe toxic side effects of conventional chemotherapeutic agents.
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