Early warning

Research to detect early-stage prostate cancer is being carried out by a European project, combining targeted microbubbles and highly sensitive ultrasound equipment.

The €2m (£1.6m) Targeted Microbubbles and Remote Ultrasound Transducer collaboration involves microbubble specialist Bracco, echographic systems developer Esaote, medical probe manufacturer Vermon, signal processing company Signal GeneriX, and academic research partners.

Dr Eric Allemann, head of microbubble development at Bracco Group, said: ‘Our technology is mainly used to create contrast agents for X-ray, MRI and ultrasound.

‘The microbubbles are a mixture of phospholipids which, using a patent method, are dispersed in aqueous media then freeze-dried. Upon reconstitution with saline, you get a dispersion of microbubbles calibrated to have a mean size of between two and four micrometres, which can be injected intravenously.’

For this project, Bracco used new methods to bind antibodies to the microbubbles, which then attach to tiny early-tumour blood vessels, increasing the sensitivity of detection.

Genoa University has a long-established collaboration with Esaote and worked alongside Signal GeneriX to contribute signal processing know-how.

Prof Andrea Trucco from Genoa’s department of biophysical and electronic engineering, said: ‘To detect a small population of microbubbles and to estimate the concentration, we need a method that cancels or minimises the response of biological tissues and amplifies the response of the microbubbles.’

To do this, the researchers exploit the fact that body tissues give a linear response to scans, and microbubbles exhibit nonlinear behaviour. There are several methods to achieve this, based on the transmission of a given sequence of pulses, the sum of which cancels any linear response.

‘In this project we selected the best of these methods for the specific microbubbles that were developed during this project for prostate cancer detection,’ said Trucco.

‘The concentration is estimated by working on the residual signal after we have cancelled out the tissue response. The signal is analysed and some temporal and spectral features of it are extracted. We then use a pattern recognition algorithm to estimate the local concentration and assess the cancer status.’

Project co-ordinator Allessandro Nencioni from Esaote said the major challenge was assembling all the elements — the microbubbles, the antibody tag and the sensor. ‘Getting everything to work together for the lab test was the most critical point,’ he said.

The project is due to run until the end of next year, at the end of which the researchers hope to have achieved a proof of concept that can be exploited in echographic systems designed to target specific microbubbles.

‘The medical centre in Innsbruck will then test the system on mice with cancer to see if we can detect and capture an image of the contrast media tag,’ Nencioni said. ‘If the results are positive, we can proceed with further research and test it in humans. But it will be several years until we can use it in patients.’

If the project is successful, it could pave the way for Bracco to develop its biosensor for other cancers, cardiac monitoring and other body systems.

‘Anywhere you can reach with micrographic contrast media you can use this process with a remote sensor — we’d use the same technique with different biomarkers,’ said Nencioni.

‘For our proof of concept we need at least two biomarkers to show we can distinguish between them.’

Berenice Baker