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A novel technique for measuring human tissue pO2 at the cellular level
Abstract:
Some electron-affinic drugs, developed as hypoxic cell radiosensitizers, become selectively bound to the molecules of hypoxic cells by metabolism. This technique has been used to identify zones of chronically hypoxic cells in multicellular spheroids and animal tumours. Tritiated-misonidazole was administered to a patient with advanced melanoma 22 h prior to the surgical resection of a large metastatic s.c. lesion growing on the face. Autoradiographic analysis of histological sections revealed zones of intense labelling by the radioactive drug, indicative of tumour cells which were chronically hypoxic. This technique appears to provide an indirect measurement of tissue pO2 at the cellular level from which estimates of the tumour hypoxic fraction can be made. These data are encouraging as regards the development of 'sensitizer-adduct' procedures for the invasive and non-invasive measurement of hypoxia in both tumours and normal tissues.
Insights
Electron-affinic drugs selectively bind to hypoxic cells, aiding in identifying and measuring tumor hypoxia. This technique shows promise for both invasive and non-invasive assessments of oxygen levels in tissues.
Area of Science:
- Oncology
- Radiochemistry
- Medical Imaging
Background:
- Hypoxic cells in tumors are resistant to radiation therapy.
- Electron-affinic drugs can selectively bind to hypoxic cells via metabolism.
- Identifying hypoxic zones is crucial for effective cancer treatment.
Purpose of the Study:
- To evaluate the use of a tritiated electron-affinic drug, misonidazole, for identifying chronically hypoxic cells in human melanoma.
- To assess the potential of 'sensitizer-adduct' techniques for measuring tumor hypoxia.
Main Methods:
- Administration of tritiated-misonidazole to a patient with advanced melanoma.
- Surgical resection of a metastatic lesion.
- Autoradiographic analysis of histological sections to detect drug localization.
Main Results:
- Autoradiography revealed intense labeling in specific zones of the tumor.
- These labeled zones correspond to chronically hypoxic tumor cells.
- The technique provides an indirect measure of tissue partial pressure of oxygen (pO2).
Conclusions:
- The 'sensitizer-adduct' technique can identify chronically hypoxic tumor cells.
- This method offers a way to estimate the tumor hypoxic fraction.
- The findings support the development of invasive and non-invasive methods for measuring tissue hypoxia.