Assuming that we could visualize pathological processes such as cancer at a very early stage and additionally distinguish the various different cell types, this would represent a giant step for personalized medicine. Xenon magnetic resonance imaging has the potential to fulfill this promise – if suitable contrast media are found that react sensitively enough to the ‘exposure’. Researchers at the Leibniz-Institut fur Molekulare Pharmakologie in Berlin have now found that a class of pumpkin-shaped molecules called cucurbiturils together with the inert gas xenon, enables particularly good image contrast – namely around 100 times better than has been possible up to now. This finding points the way to the tailoring of new contrast agents to different cell types and has the potential to enable molecular diagnostics even without tissue samples in the future.
Personalized medicine instead of one treatment for all – especially in cancer medicine, this approach has led to a paradigm shift. Molecular diagnostics is the key that will give patients access to tailor-made therapy. However, if tumours are located in poorly accessible areas of the body or several tumour foci are already present, this often fails due to a lack of sufficient sensitivity of the diagnostic imaging. But such sensitivity is needed to determine the different cell types, which differ considerably even within a tumour. Although even the smallest of tumour foci and other pathological changes can be detected using the PET-CT, a differentiation according to cell type is usually not possible.
Scientists from the FMP are therefore focusing on xenon magnetic resonance imaging: The further development of standard magnetic resonance imaging makes use of the ‘illuminating power’ of the inert gas xenon, which can provide a 10,000-fold enhanced signal in the MRI. To do this, it must be temporarily captured by so-called ‘cage molecules’ in the diseased tissue. This has been more or less successful with the molecules used to date, but the experimental approach is still far from a medical application.
The research group led by Dr. Leif Schroder at the Leibniz-Institut fur Molekulare Pharmakologie (FMP) has now discovered a molecule class for this purpose that eclipses all of the molecules used to date. Cucurbituril exchanges around 100 times more xenon per unit of time than its fellow molecules, which leads to a much better image contrast. ‘It very quickly became clear that cucurbituril might be suitable as a contrast medium,’ reports Leif Schroder. ‘However, it was surprising that areas marked with it were imaged with a much better contrast than previously.’ The explanation is to be found in the speed. Upon exposure, so to speak, cucurbituril generates contrast more rapidly than all molecules used to date, as it only binds the xenon very briefly and thus transmits the radio waves to detect the inert gas to very many xenon atoms within a fraction of a second. In this way, the inert gas is passed through the molecule much more efficiently.
In the study the world’s first MRI images with cucurbituril have been achieved. With the aid of a powerful laser and a vaporized alkali metal, the researchers initially greatly strengthened the magnetic properties of normal xenon. The hyperpolarized gas was then introduced into a test solution with the cage molecules. A subsequent MRI image showed the distribution of the xenon in the object. In a second image, the curcurbituril together with radio waves destroyed the magnetization of the xenon, leading to dark spots on the images.
‘Comparison of the two images demonstrates that only the xenon in the cages has the right resonance frequency to produce a dark area,’ explains Schroder. ‘This blackening is possible to a much better degree with cucurbituril than with previous cage molecules, for it works like a very light-sensitive photographic paper. The contrast is around 100 times stronger.’
Initial tests were performed with cell material in which cucurbituril is also able to detect a certain enzyme that commonly occurs in cancer cells. On the basis of the enzyme reaction, it is possible to conclude the malignancy of the cells. What is special about this is that relatively little cell material is then sufficient to image the tumour cells in the MRI. The researchers believe that it may be possible to detect even very small tumour foci using this new method in the future. However, there is still a long way to go. To begin with, animal studies must be conducted to determine whether it is possible to transfer the test results obtained to date to the living organism. If so, they can be used to develop highly sensitive contrast media that are able to mark further enzymes and thus a range of different cell types.

Leibniz-Institut fur Molekulare Pharmakologiehttp://tinyurl.com/h2bn6go

Approximately a quarter of women with HER2 positive breast cancer, who were treated with a combination of the targeted drugs lapatinib and trastuzumab before surgery and chemotherapy, saw their tumours shrink significantly or even disappear, according to results from a clinical trial.

The University of Manchester

In an interdisciplinary collaboration between prominent academic and industry investigators, researchers have discovered a novel method for repositioning an FDA-approved anti-cancer compound so it can specifically target liver cancer tumours. A

Twice as many patients with non-serious injuries, such as fractures or neck strain, are undergoing CT scans in emergency departments at California hospitals, according to a UCSF-led study, which tracked the use of the imaging from 2005 to 2013.
While CT scans enable clinicians to swiftly pinpoint life-threatening conditions, exposure to its ionizing radiation is associated with an increased risk of cancer. According to a 2009 report by the FDA, a single CT scan may be associated with a fatal cancer in one in 2,000 patients.
In the study, researchers at UCSF and Stanford studied more than 8 million adult patient visits at 348 state hospitals, using data from the California Office of Statewide Health Planning and Development. These patients had been discharged after being seen in emergency departments for injuries such as minor falls or low-impact vehicle accidents. The study found that 3.51 percent of patients underwent at least one CT scan in 2005, versus 7.17 percent in 2013.
‘The reasons for this increase are multifactorial,’ said senior author Renee Hsia, MD, professor of emergency medicine and health policy at UCSF. ‘They range from defensive medicine practices, the superior diagnostic accuracy of CT scans compared with X-rays, to their increased availability and convenience in emergency departments, and the demand to expedite discharge of patients.’
The authors noted that CTs were more likely to be ordered in hospitals that were designated high-level trauma centres. Some 39 percent of those in the study were ordered at level I and II trauma centres, compared with 3 percent at low-level centres.
‘This may reflect an underlying work culture largely centred around the management of severely injured patients, guided by standard trauma CT protocols, and also the fact that level I and II trauma centres see sicker patients,’ the authors wrote in their paper.
Also disproportionately visible were patients between the ages of 18 and 24, ‘those at greatest risk for radiation,’ wrote the authors, as well as those over 45. ‘With the aging of the U.S. population, physicians may be influenced toward greater advanced imaging even in the case of low-mechanism injuries, given the atypical presentations and more serious pathology that older adults may have,’ said Hsia.
The authors reported an upswing in the use of CTs from 2005 to 2009, followed by a gradual decline to 2011 – reflecting awareness of overuse – which was preceded by a resurgence from 2011 to 2013 that almost reached the zenith of 2009.
‘The message for both patients and physicians is that there are long-term risks associated with radiation exposure and there may be situations where imaging is not definitively warranted or beneficial,’ said Hsia.

University of California – San Francisco http://tinyurl.com/hp4525h

UHCW pathologist David Snead and scientists in Coventry are now using technology that could revolutionize how some cancers are diagnosed.
A high-tech computer system is able to read samples of human tissue and aid pathologists in the identification of minute changes in cells that can indicate cancer is present. More than 10,000 slides were examined in the first phase of the study which shows that pathologists are as good at accurately diagnosing cancer on a computer as they are with a microscope.
The ground breaking technology has the power to help pathologists grade some types of tumours, including lung, prostate and bladder tumours with precision. In prostate cancer, for example, this could make the difference between someone being offered surgery rather than drug based treatments.
The computer system known as The Omnyx Precision Solution, can help pathologists to see the small differences in cells in the same way that they have currently been using a microscope, allowing them to make sound decisions on many aspects of cancer diagnosis.
The Omnyx system digitizes slides which are traditionally placed on a microscope so that pathologists can look at them on a computer. Once on the computer, the UHCW scientists have written programmes which will separate normal from abnormal samples.
David Snead said: ‘I am delighted that University Hospital, Coventry has led this ground breaking study. This provides even greater evidence that digital pathology really works, and works well. The introduction of digital pathology has fantastic potential benefits for patients. We can expect to be able to read samples more quickly than before, and the big advantage is that we can use the computer to easily manipulate an image or its data. For some patients, this additional information may change how their disease is managed.’

University Hospitals Coventry http://tinyurl.com/gw4c993