# Electron-Induced Fragmentation of 5-Iodouridine: Implications for Enhanced Radiotherapy

## TL;DR

This paper shows how 5-iodouridine breaks apart when hit by electrons during radiation, which could make cancer treatments more effective.

## Contribution

The study reveals a new mechanism of radiosensitization via electron-induced fragmentation of 5-iodouridine.

## Key findings

- Low-energy electrons efficiently dissociate 5-iodouridine into reactive fragments.
- 5-iodouridine causes significantly more DNA damage compared to thymidine and 5-fluorouridine.
- The findings suggest combining 5-iodouridine with cisplatin or gold nanoparticles could enhance radiotherapy.

## Abstract

5-Iodouridine is
a known and potentially efficient radiosensitizer;
however, it has not been considered for clinical use because of its
poor metabolic incorporation into DNA. Recent development of a novel
pro-drug, ropidoxuridine, has improved the bioavailability of this
halogenated nucleoside, although the exact mechanism of its radiosensitizing
action remains not fully elucidated. Here, we demonstrate that low-energy
electronsabundantly generated along radiation tracksefficiently
dissociate the halogenated nucleoside via the primary pathway (99%),
producing an iodine anion and a uridine-yl• neutral
radical, with a high approximate DEA cross section of (2.7 ±
1.9)×10–14 cm2. The latter, known
to be highly reactive, subsequently induces hydrogen abstraction,
leading to DNA strand breaks. The damage induced in 5IUrd by low-energy
electrons is found to be about 700 times greater than that in thymidine
and about 4 times that of the clinically used 5-fluorouridine. These
findings may contribute to the development of future cancer therapy
strategies by synergistically combining 5IUrd with cisplatin or gold
nanoparticles, which act as a source of secondary low-energy electrons
during radiation therapy.