Molecular imaging of tumor hypoxia: Evolution of nitroimidazole radiopharmaceuticals and insights for future development

• Published in: Bioorganic chemistry 2023-10, Vol.139, p.106687-106687, Article 106687
• Main Authors: Mittal, Sweety, Mallia, Madhava B.
• Format: Article
• Language: English
• Subjects: Hypoxia; Hypoxia imaging; Image guided therapy; Nitroimidazole; Radioisotopes; Radiopharmaceuticals
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2023.106687

Though growing evidence has been collected in support of the concept of dose escalation based on the molecular level images indicating hypoxic tumor sub-volumes that could be radio-resistant, validation of the concept is still a work in progress. Molecular imaging of tumor hypoxia using radiopharmaceuticals is expected to provide the required input to plan dose escalation through Image Guided Radiation Therapy (IGRT) to kill/control the radio-resistant hypoxic tumor cells. The success of the IGRT, therefore, is heavily dependent on the quality of images obtained using the radiopharmaceutical and the extent to which the image represents the true hypoxic status of the tumor in spite of the heterogeneous nature of tumor hypoxia. Available literature on radiopharmaceuticals for imaging hypoxia is highly skewed in favor of nitroimidazole as the pharmacophore given their ability to undergo oxygen dependent reduction in hypoxic cells. In this context, present review on nitroimidazole radiopharmaceuticals would be immensely helpful to the researchers to obtain a birds-eye view on what has been achieved so far and what can be tried differently to obtain a better hypoxia imaging agent. The review also covers various methods of radiolabeling that could be utilized for developing radiotracers for hypoxia targeting applications.