The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

Abstract

Tumor hypoxia is a well-established biological phenomenon that affects the curability of solid tumors, regardless of treatment modality. Especially for head and neck cancer patients, tumor hypoxia is linked to poor patient outcomes. Given the biological problems associated with tumor hypoxia, the goal for clinicians has been to identify moderately to severely hypoxic tumors for differential treatment strategies. The ''gold standard'' for detecting and characterizing of tumor hypoxia are the invasive polarographic electrodes. Several less invasive hypoxia assessment techniques have also shown promise for hypoxia assessment. The widespread incorporation of hypoxia information in clinical tumor assessment is severely impeded by several factors, including regulatory hurdles and unclear correlation with potential treatment decisions. There is now an acute need for approved diagnostic technologies for determining the hypoxia status of cancer lesions, as it would enable clinical development of personalized, hypoxia-based therapies, which will ultimately improve outcomes. A number of different techniques for assessing tumor hypoxia have evolved to replace polarographic pO 2 measurements for assessing tumor hypoxia. Several of these modalities, either individually or in combination with other imaging techniques, provide functional and physiological information of tumor hypoxia that can significantly improve the course of treatment. The assessment of tumor hypoxia will be valuable to radiation oncologists, surgeons, and biotechnology and pharmaceutical companies who are engaged in developing hypoxia-based therapies or treatment strategies. Antioxid. Redox Signal. 21, 1516-1554.

Synthesis, Characterization, and Nanoencapsulation of Tetrathiatriarylmethyl and Tetrachlorotriarylmethyl (Trityl) Radical Derivatives—A Study To Advance Their Applicability as in Vivo EPR Oxygen Sensors

“…Glassware for reactions under argon atmosphere was oven-dried at 100 °C for 2 h prior to use, 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 28 2,2,6,6-Tetramethylbenzo [1,2-d:4,5-d']bis [1,3]dithiole (2a). 10,40,42 HBF 4 (54 % in Et 2 O, 10 mL, 37.0 mmol) was added to a solution of 1,2,4,5-tetra(tertbutylthio)benzene (1) (16.0 g, 37.2 mmol) in toluene (500 mL).…”

“…After cooling, a saturated NaHCO 3 solution (100 mL) was added carefully, the organic layer was separated and the aqueous layer extracted three times with ethyl acetate (EA). The combined organic layers were dried over MgSO 4 [1,2-d:4,5-d']bis [1,3]dithiole (2b). 9,21,22 The rocedure used for Tris [2,2,6,6-tetramethylbenzo [1,2-d:4,5-d']bis( [1,3]dithiole)-4-yl]methanol (3a).…”

“…The combined organic layers were dried over MgSO 4 [1,2-d:4,5-d']bis [1,3]dithiole (2b). 9,21,22 The rocedure used for Tris [2,2,6,6-tetramethylbenzo [1,2-d:4,5-d']bis( [1,3]dithiole)-4-yl]methanol (3a). 10 …”

“…Compound 2b (3.49 g, 11.7 mmol), n-BuLi (4.7 mL, 11.7 mmol) and methyl chloroformate (0.3 mL, 3.9 mmol) in dry Tris [8-ethoxycarbonyl-2,2,6,6-tetramethylbenzo [1,2-d:4,5-d']bis( [1,3]dithiole)-4-yl]methanol (4). 23,40 Compound 3a (500 mg, 0.57 mmol) and TMEDA (0.85 mL, 5.7 mmol) were mixed in dry n-hexane (5 mL) under argon atmosphere and cooled to 0 °C.…”

“…[1][2][3] Various oxygen measurement techniques have been developed, but especially in vivo oximetry is still challenging. EPR (ESR) oximetry offers several advantages as it enables direct, non-invasive, and repeatable oxygen measurements.…”