Light treats deep into tissue

Photodynamic therapy (PDT), the irradiation of photosensitive materials to generate toxic free radicals, is a promising cancer treatment. But only in places where light can reach, such as superficial or endoscope-accessible lesions. Researchers at Washington University School of Medicine are working to apply PDT deep into tissue, by delivering a light source directly to the tumour cells. The idea is to use fluorodeoxyglucose (FDG), a common PET tracer, to produce Cerenkov light, which then activates an oxygen-independent photosensitizer: titanium dioxide nanoparticles. To increase the potency, the researchers added the investigational cancer drug titanocene (which interacts with low-intensity light and creates free radicals) to the nanoparticle surface. They also coated the particles with transferrin to target them to the tumour cells.

Tests in tumour-bearing mice revealed that mice injected with FDG plus the tumour-seeking nanoparticles carrying titanocene survived for 50 days, compared with an average of 15 days for untreated mice. Fifteen days after Cerenkov radiation-induced therapy (CRIT), treated tumours were eight times smaller than those in untreated mice (Nature Nanotech. doi: 10.1038/nnano.2015.17). The team now plans a small clinical trial to evaluate the readily available components of this strategy, beginning with FDG combined with the cancer drug.

First in-human nanotherapy brain cancer trial launched

Earlier this month, David Williams became the first human to have a new radiation treatment implanted in the centre of his brain tumour. The technology, developed at the Cancer Therapy & Research Center at the UT Health Science Center, uses a thin catheter to insert 100 nm-diameter, highly-radioactive liposomes directly into the tumour. At his first follow-up appointment, Williams said that he did not experience the side-effects normally associated with conventional radiotherapy, which also irradiates healthy tissue. "The technology is unique," said neuro-oncologist Andrew Brenner. "Only we can load the liposomes to these very high radioactivity levels."

One challenge of this approach is getting the nano-liposomes into the brain. To do this, the team designed an improved catheter that can deliver small quantities to precise locations, noting that they were "very pleased already with delivery in our first case". Brenner, the clinical trial leader, expects to start the second patient on the study within a month. "The main limitation right now is we have to start with small-sized tumours, until we get a better handle on our delivery methods, to make sure we can cover larger tumours," he said.

Ultrasound restores memory in mice with Alzheimer's

Researchers at the Queensland Brain Institute have used ultrasound to help clear amyloid-β plaques, responsible for the memory loss and cognitive decline in Alzheimer's disease, from the brains of mice. Gerhard Leinenga and Jürgen Götz combined focused ultrasound and injected microbubbles, which vibrate in response to the ultrasound, to temporarily open the blood-brain barrier in amyloid-β plaque-forming mice. Repeated application of this technique over several weeks led to almost complete clearance of the neurotoxic plaques in 75% of mice, without damaging brain tissue. Compared to untreated mice, the treated mice performed better in three memory tests (Sci. Transl. Med. 7 278ra33).

Analysis of brain tissues revealed that the ultrasound stimulates microglial cells, immune cells that engulf cellular debris, to ingest more plaque. "We're extremely excited by this innovation of treating Alzheimer's without using drug therapeutics," said Götz. "This treatment restored memory function to the same level of normal healthy mice." The authors next plan to test the technique in a sheep model of Alzheimer's disease, ahead of human clinical trials, which are at least two years away.

SRS alone is best for some brain metastases patients

Cancer patients with limited brain metastases (one to four tumours) who are 50 years old and younger should receive stereotactic radiosurgery (SRS) without whole-brain radiotherapy (WBRT), according to a study published in the Red Journal. The authors performed a meta-analysis of patient data from the three largest randomized clinical trials of SRS and WBRT conducted to date. A total of 364 patients from the three trials were evaluated. Of those, 51% were treated with SRS alone and 49% received both SRS and WBRT; 19% were 50 years old and younger (Int. J. Radiat. Oncol. Biol. Phys. 91 710).

The study revealed that patients aged 50 and younger who received SRS alone had a median survival of 13.6 months after treatment, a 65% improvement from the 8.2 months for such patients treated with SRS plus WBRT. Patients aged above 50 had a median survival of 10.1 months when treated with SRS alone, and 8.6 months for SRS plus WBRT. "We expected to see a survival advantage favouring combined therapy of SRS and WBRT," said lead author Arjun Sahgal, from the University of Toronto and the Odette Cancer Centre. "However, these data clearly demonstrate the benefit for SRS alone to improve survival for our younger patients with limited brain metastases."

PET/CT outdoes SPECT for heart disease diagnosis

Using cardiac PET/CT to diagnose coronary artery disease and other heart disorders is significantly more accurate, less expensive and safer than traditional SPECT methods, according to a study from the Intermountain Medical Center Heart Institute. The researchers compared outcomes of patients at the Intermountain Heart Institute who received SPECT scans in 2012 with those scanned with PET in 2013, selecting 197 SPECT patients and 200 PET/CT patients who had both an imaging test and a heart catheter. They found that cardiac PET/CT diagnosed heart problems with certainty 88% of the time, while SPECT gave a clear diagnosis only 30% of the time.

If an imaging procedure is inconclusive, physicians must then use alternative invasive diagnostic techniques like coronary angiograms and cardiac catheters. Cardiac PET/CT reduced the need for such additional procedures by more than 50%. The study also revealed that SPECT gave a false positive about 6% of the time, while cardiac PET/CT imaging gave no false positives during the study period. In addition, cardiac PET/CT reduced radiation exposure from the 30 mSv typically delivered in a SPECT scan to just 2 mSv. Results were presented at the recent American College of Cardiology 64th Annual Scientific Session.

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