Drug development: radical imaging

Use of nitroxyl radicals allows safe real-time imaging of the movement of drugs in the brain. A vital step in process of approving new pharmaceuticals is imaging of their blood-brain barrier

(BBB) permeability. This drug-mapping in the brain enables definition of required dosages and target-specific effects. Conventional measurement methods for BBB permeability are usually

invasive, time-consuming and costly, and in vitro models are often used instead. In spite of the risks associated with human Radio-labelling, it is still currently the only non-invasive in

vivo method used. Now, Rumiana Bakalova and colleagues1 at the National Institute of Radiological Sciences, Chiba, Japan and Trakia University, Bulgaria report on the development of a new

non-invasive in vivo method for measuring BBB permeability using nitroxyl radicals and magnetic resonance imaging (MRI). Their approach is non-radioactive, environmentally friendly, and can

be used to map drugs in the brain in real time. Nitroxyl radicals have paramagnetic properties, which enable them to be monitored in the body using MRI. Furthermore, the radicals exhibit low

toxicity and are relatively harmless to living organisms. Interestingly, the most commonly used nitroxyl radical is currently in Phase I of clinical trials for the prevention of alopecia in

cancer patients treated with radiotherapy. Fig. 1: Imaging the nitroxyl-labelled drug in the brain. The group took a conventional anti-cancer drug, which was known to permeate the BBB, and

synthesized an amended version incorporating a nitroxyl radical. After checking that the nitroxyl radicals were securely bonded to the anti-cancer part of the molecules, the researchers

injected the modified drug into healthy mice. The labelled drug was easily visible using the MRI scanner (Fig.1). They monitored the progress of the drug and found that the additional

radicals did not affect its distribution in the brain. This approach has additional advantages. “Nitroxyl radicals are well-known for their sensitivity to the redox potential of cells and

tissues,” says Bakalova. “ Thus, the modulation of the MRI signal of nitroxyl-labelled drugs could give information about the redox state (status) of brain tissue. This is important for the

detection and therapy of many diseases that are revealed by unbalanced redox potential.” In the future, the group will optimize the molecules used by increasing their MRI contrast, as well

as apply the approach to other organs. REFERENCES * Zhelev, Z. _et al_. Nitroxyl radicals as low toxic spin-labels for non-invasive magnetic resonance imaging of blood–brain barrier

permeability for conventional therapeutics. _Chem. Commun._ 53, 53 (2009). Article  Google Scholar  Download references ADDITIONAL INFORMATION This research highlight has been approved by

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ARTICLE Drug development: Radical imaging. _NPG Asia Mater_ (2009). https://doi.org/10.1038/asiamat.2009.139 Download citation * Published: 25 February 2009 * DOI:

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