Influence of 2-Nitroimidazoles in the Response of FaDu Cells to Ionizing Radiation and Hypoxia/Reoxygenation Stress.

Cellular adaptations to hypoxia promote resistance to ionizing radiation (IR). This presents a challenge for treatment of head and neck cancer (HNC) that relies heavily on radiotherapy. Standard radiosensitizers often fail to reach diffusion-restricted hypoxic cells, whereas nitroimidazoles (NIs) [such as iodoazomycin arabinofuranoside (IAZA) and fluoroazomycin arabinofuranoside (FAZA)] can preferentially accumulate in hypoxic tumours.

The chemistry and radiochemistry of hypoxia-specific, radiohalogenated nitroaromatic imaging probes.

Hypoxia is prevalent in many solid tumors. Hypoxic tumors tend to exhibit rapid growth and aberrant vasculature, which lead to oxygen (O2) depletion and impaired drug delivery. The reductive environment in hypoxic tumors alters cellular metabolism, which can trigger transcriptional responses; induce genetic alterations; promote invasion, metastasis, resistance to radiotherapy and chemotherapy, tumor progression, and recurrence; and leads to poor local control and reduced survival rates.

Synthesis of 1-beta-D-(5-deoxy-5-iodoarabinofuranosyl)-2-nitroimidazole (beta-IAZA): a novel marker of tissue hypoxia.

The present work describes the synthesis of the beta-isomer of 1-alpha-D-(5-deoxy-5-iodoarabinofuranosyl)-2-nitroimidazole (IAZA). Radioiodinated IAZA ((123)I-IAZA) has been extensively studied as a radiopharmaceutical for the diagnosis of regional and/or focal tissue hypoxia in a variety of clinical pathologies. The beta-anomer of IAZA, 1-beta-D-(5-deoxy-5-iodoarabinofuranosyl)-2-nitroimidazole (beta-IAZA, 1), was synthesized via an unconventional route starting from 1-beta-D-(ribofuranosyl)-2-nitroimidazole (AZR), with a change of configuration at the C-2'-position to afford 1-beta-D-(arabinofuranosyl)-2-nitroimidazole (beta-AZA, 7).