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31P changes as a measure of therapy response in human osteosarcomas implanted into nude mice
H Kang1, J R Ballinger, C Sweeney
1Department of Radiology, University of Florida, Gainesville 32610.
Abstract:
Our objective was to determine whether changes in PME and PCr/Pi can be used to predict lack of tumor response to chemotherapy in a murine model of human osteosarcoma. A chemotherapy-sensitive human osteosarcoma cell line was implanted into the flank of 22 nude mice. Cisplatin was administered to 11 of the mice 9 days postimplantation. 31P MR spectroscopy was performed pre- and post-chemotherapy in both sets of mice. Statistically significant changes in PCr/Pi occur from post-chemotherapy in the treated mice, but not in the untreated mice during the same time. Change in PME parallels changes in tumor volume. Changes in PCr/Pi predict lack of chemotherapy treatment in human osteosarcoma implanted into nude mice with a specificity of 80% and a sensitivity of 63%. The change in PCr/Pi occurs prior to any changes in volume of the tumor [corrected].
Insights
Phosphocholine to inorganic phosphate (PCr/Pi) changes can predict chemotherapy resistance in osteosarcoma. This finding in a mouse model may help identify non-responding tumors earlier.
Area of Science:
- Biomedical Engineering
- Oncology
- Medical Imaging
Background:
- Osteosarcoma is a challenging bone cancer.
- Predicting chemotherapy response is crucial for treatment efficacy.
- Current methods for predicting response can be limited.
Purpose of the Study:
- To investigate if changes in phosphomonoesters (PME) and the ratio of phosphocreatine to inorganic phosphate (PCr/Pi) can predict chemotherapy resistance in osteosarcoma.
- To evaluate the utility of 31P MR spectroscopy in a murine model for assessing treatment response.
Main Methods:
- Human osteosarcoma cells were implanted in nude mice.
- Cisplatin chemotherapy was administered to a subset of mice.
- 31P MR spectroscopy was performed before and after chemotherapy.
- Changes in PME and PCr/Pi levels were correlated with tumor volume and treatment response.
Main Results:
- Statistically significant changes in PCr/Pi were observed post-chemotherapy in treated mice, but not in untreated mice.
- Changes in PME correlated with tumor volume changes.
- PCr/Pi changes predicted lack of chemotherapy response with 80% specificity and 63% sensitivity.
- PCr/Pi alterations preceded detectable changes in tumor volume.
Conclusions:
- Changes in PCr/Pi are a potential early predictor of chemotherapy resistance in osteosarcoma.
- 31P MR spectroscopy offers a non-invasive method to assess treatment response.
- These findings may aid in tailoring chemotherapy regimens for osteosarcoma patients.