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Published on: March 6, 2018
Combinatorial effect of radium-223 and irreversible electroporation on prostate cancer bone metastasis in mice
Raniv D Rojo1,2, Joy Vanessa D Perez1,2, Jossana A Damasco1
1Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background:
Metastatic prostate cancer in bone is difficult to treat as the tumor cells are relatively resistant to hormonal or chemotherapies when compared to primary prostate cancer. Irreversible electroporation (IRE) is a minimally invasive ablation procedure that has potential applications in the management of prostate cancer in bone. However, a common limitation of IRE is tumor recurrence, which arises from incomplete ablation that allows remaining cancer cells to proliferate. In this study, we combined IRE with radium-223 (Ra-223), a bone-seeking radionuclide that emits short track length alpha particles and thus is associated with reduced damage to the bone marrow and evaluated the impact of the combination treatment on bone-forming prostate cancer tumors.
Methods:
The antitumor activity of IRE and Ra-223 as single agents and in combination was tested in vitro against three bone morphogenetic protein 4 (BMP4)-expressing prostate cancer cell lines (C4-2B-BMP4, Myc-CaP-BMP4, and TRAMP-C2-BMP4). Similar evaluation was performed in vivo using a bone-forming C4-2B-BMP4 tumor model in nude mice.
Results:
IRE and Ra-223 as monotherapy inhibited prostate cancer cell proliferation in vitro, and their combination resulted in significant reduction in cell viability compared to monotherapy. In vivo evaluation revealed that IRE with single-dose administration of Ra-233, compared to IRE alone, reduced the rate of tumor recurrence by 40% following initial apparent complete ablation and decreased the rate of proliferation of incompletely ablated tumor as quantified in Ki-67 staining (53.58 ± 16.0% for IRE vs. 20.12 ± 1.63%; for IRE plus Ra-223; p = 0.004). Histological analysis qualitatively showed the enhanced killing of tumor cells adjacent to bone by Ra-223 compared to those treated with IRE alone.
Conclusion:
IRE in combination with Ra-223, which enhanced the destruction of cancer cells that are adjacent to bone, resulted in reduction of tumor recurrence through improved clearance of proliferative cells in the tumor region.
Insights
Combining irreversible electroporation (IRE) with radium-223 (Ra-223) significantly reduces prostate cancer recurrence in bone. This novel approach enhances tumor cell destruction, offering a more effective treatment for metastatic bone cancer.
Area of Science:
- Oncology
- Medical Physics
- Radiochemistry
Background:
- Metastatic prostate cancer in bone presents treatment challenges due to tumor cell resistance to conventional therapies.
- Irreversible electroporation (IRE) is a minimally invasive ablation technique with potential for prostate cancer management.
- Tumor recurrence after IRE, stemming from incomplete ablation, is a significant limitation.
Purpose of the Study:
- To evaluate the combined efficacy of IRE and radium-223 (Ra-223) against bone-forming prostate cancer.
- To assess the impact of this combination therapy on tumor recurrence and cell proliferation.
Main Methods:
- Antitumor activity was tested in vitro against BMP4-expressing prostate cancer cell lines.
- In vivo studies utilized a bone-forming prostate cancer tumor model in nude mice.
- Combination therapy involved IRE and single-dose Ra-223 administration.
Main Results:
- The combination of IRE and Ra-223 significantly reduced cancer cell viability in vitro compared to monotherapy.
- In vivo, IRE with Ra-223 reduced tumor recurrence by 40% post-ablation compared to IRE alone.
- Combination treatment decreased tumor cell proliferation (Ki-67 staining) and enhanced tumor cell killing adjacent to bone.
Conclusions:
- Combining IRE with Ra-223 improves the clearance of proliferative cells in the tumor region.
- This combination therapy reduces tumor recurrence by enhancing cancer cell destruction, particularly near bone.
- The findings suggest a promising therapeutic strategy for metastatic prostate cancer in bone.
