Researchers presenting a preclinical study at the 2017 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) demonstrated the efficacy and optimal dose for targeted photodynamic therapy (tPDT) to treat prostate cancer before and during surgery. Prostate-specific membrane antigen (PSMA) was targeted with an anti-PSMA antibody radiolabeled with the tracer indium-111 (111In) and coupled with specialized photosensitizers that cause cell destruction upon exposure to near-infrared (NIR). The combined formula is 111In-DTPA-D2B-IRDye700DX.
“Coupling the photosensitizer to an imaging agent that targets PSMA on the tumour surface makes it possible to selectively and effectively destroy prostate tumour remnants and micrometastases while surrounding healthy tissues remain unaffected,” said Susanne Lütje, MD, PhD, lead author of the study from the Department of Radiology and Nuclear Medicine at Radboud University Medical Center in Nijmegen, the Netherlands, and the Clinic for Nuclear Medicine at University Hospital Essen, Germany.
This technique optimizes prostate cancer care by allowing visualization of tumours prior to surgery, by providing real-time guidance to surgeons in the operating room, and by priming tumours for photodynamic therapy when surgery isn’t enough or risks damage to sensitive structures.
A gamma probe is used to detect PSMA-expressing tumour cells. Photosensitizers can then be activated with light in the near-infrared wavelength, which causes them to emit fluorescence, or oxygen radicals, that damage PSMA over-expressing tumour tissues.
Study results showed effective localization of the drug at the site of tumours, as well as effective imaging and photodynamic therapy via near-infrared exposure in mice. Further study in humans is needed before this procedure could be made available for prostate cancer patients.
“In the future, this novel approach to prostate cancer could significantly improve the effectiveness of treatment, reduce recurrent disease and ultimately prolong survival and protect quality of life for patients,” said Lütje.

Society of Nuclear Medicine and Molecular Imaging
www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=24264

For the first time, researchers have shown that using Magnetic Resonance Imaging (MRI) can effectively identify bone marrow cancer (myelofibrosis) in an experimental model. The finding may change the way this disease is diagnosed which is now through invasive bone marrow biopsies.
Myelofibrosis is a slow evolving condition hallmarked by increased myeloid cells and in the case of primary myelofibrosis, with an excessive number of large bone marrow cells called megakaryocytes. The pathology also is characterized by structural abnormality of the bone marrow matrix, which at end-stage manifests in excessive deposition of reticulin fibres and cross-linked collagen in the bone marrow, suppression of normal blood cell development and bone marrow failure. Currently the diagnosis is made via an invasive bone marrow biopsy and histophatology to assess cellularity and reticulin deposition in the marrow.
Researchers at Boston University School of Medicine (BUSM) led by Katya Ravid, PhD, designed and tested whether a T2-weighted MRI could detect bone marrow fibrosis in an experimental model. The group was able to show that an MRI could detect a pre-fibrotic state of the disease with a clear bright signal, as well as progressive myelofibrosis. The investigators proposed that the abundance of large megakaryocytes contribute to the signal, since in T2-weighted MR-images, increased water/proton content, as in increased cellularity, yield high (bright) MR-signal intensity.
This is the first study to evaluate a T2-weighted MRI in an experimental model of myelofibrosis with examination of potential sources of the MRI signal, researchers said. “Our study provides proof-of-concept that this non-invasive modality can detect pre-fibrotic stages of the disease,” said Ravid, professor of medicine and biochemistry at BUSM. “It is intriguing to speculate that future pre-biopsy MRI of the human pathology might guide in some cases decisions on if and where to biopsy,” she added.

Boston University School of Medicinehttp://tinyurl.com/y74qq8pv

A potentially life-saving treatment for sepsis has been under our noses for decades in the non-steroidal anti-inflammatory drugs (NSAIDs) most people have in their medicine cabinets, a new University of Colorado Boulder study has found.

More than 30 billion doses of non-steroidal anti-inflammatory drugs (NSAIDS) are taken annually in the United States.
Each year more than 1 million people in the United States contract sepsis, an overwhelming immune response to infection. It kills as many as half of those who contract it, sometimes within days, according to the National Institutes of Health. As the number of cases rises, particularly in intensive care units, pharmaceutical companies have been scrambling to develop a drug to combat the condition.

‘NSAIDS like ibuprofen and aspirin are among the most prevalent pharmaceuticals worldwide, with over 30 billion doses taken annually in the United States alone. But their precise mechanisms of action are not entirely understood,’ said Hang Hubert Yin, a biochemistry professor at CU Boulder’s BioFrontiers Institute and lead author of the new paper, published today in Cell Chemical Biology. ‘We provide the first evidence for a novel mechanism of action for NSAIDS, one we believe could have a direct impact on people’s lives.’

Researchers have long known that NSAIDs work in part by inhibiting an enzyme called cyclooxygenase (COX). They’ve also known that these NSAIDs can come with serious side effects. Some NSAIDs have been removed from the market after showing they boosted risk of heart attack and stroke.

But Yin’s research found that a subgroup of NSAIDs also act strongly and independently on another family of enzymes, caspases, which reside deep within the cell and have recently been found to play a key role in aggressive immune responses, like sepsis.

‘For instance, some chemicals derived from bacteria actually penetrate the cell and trigger the caspase response, prompting the cell to commit suicide. This also is known as apoptosis,’ said Yin. ‘Such activation, in turn, potentially causes inflammation.’

After the disappointing failure of late-stage clinical trials of anti-sepsis drugs targeting an immune receptor called toll-like receptor 4 (TLR4), located on the surface of cells, Yin and other scientists began to wonder if the key to halting the disease was to develop an antiseptic therapy that simultaneously targets caspases.

As a first step, his team screened 1,280 existing FDA-approved drugs for caspase-inhibiting activity. Of the 27 that lit up, half were NSAIDs. NSAIDs also comprised eight of the top 10 most potent caspase inhibitors.

‘It was a complete surprise,’ said Yin.

He and study co-author Ding Xue, a professor in the department of Molecular Cellular and Developmental Biology, then used biochemical and biophysical assays in the lab, as well as experiments with roundworms to test the theory further.

‘We showed that NSAIDs were effective in delaying cell death in worms, presumably by blocking caspase activity.’

It remains questionable whether existing NSAIDs, perhaps in higher doses, could be used to treat sepsis. The risk of side effects may be too great, said Yin. But he is already working on follow-up studies looking at whether new sepsis drugs could be developed combining caspase-inhibiting NSAIDS and TLR4 inhibitors.

University of Colorado at Boulders www.colorado.edu/today/2017/02/23/common-drugs-similar-ibuprofen-could-help-treat-sepsis-study-suggests

Michigan researchers will look at the ability of high intensity ultraviolet light delivered by Xenex Germ-Zapping Robots to protect patients from deadly superbugs, such as Clostridium difficile, found on surfaces.
Patients are vulnerable to hospital-acquired infections – infections they can get while staying at a medical facility. Significant progress has been made in preventing some infection types, but they continue to be a major threat nationwide.
At the end of two years, researchers will report on rates of hospital-acquired infections in units where pulsed xenon UV light (PX-UV) was added to cleaning routines compared to units where a sham UV disinfection system was added to standard cleaning.
They’ll measure if cleaning plus PX-UV reduced the number of infections from drug-resistant organisms including C.difficile, vancomycin-resistant enterococci (VRE), Klebsiella pneumonia, Escherichiae coli producing extended-spectrum betalactamases (ESBLs), methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii.
Hospital cleanliness is recognized as a critically important process to help prevent hospital-acquired infections. It involves extensive cleaning and disinfection after a patient has been discharged and before the next patient has been admitted to the room.
PX-UV lamps in the robot produce a flash of germicidal light in millisecond pulses, damaging the cell structure and stopping the DNA repair mechanisms for most pathogens.
The unique design of the study, which is double-blinded and sham-controlled, makes it the first to examine the clinical impact of adding PX-UV to hospital cleaning routines.

Michigan Medicine http://tinyurl.com/yblkwdge

Specialist antenatal clinics for severely obese mums-to-be can help cut rates of pregnancy complications, research has found.
Women who received the specialist care were eight times less likely to have a stillbirth.
Health experts say the clinic helps them to spot signs of complications sooner, so that women can be given appropriate treatment. It also helps them to pinpoint those who need to be induced early or undergo an elective caesarean to avoid problems during labour.
The team tracked more than 1000 pregnant women classed as being severely obese during pregnancy because they had a body mass index (BMI) of 40 or above.
Around half of the women attended a specialist obesity clinic while the others received standard antenatal care.
Those that attended the obesity clinic were treated by a team that included obstetricians, specialist midwives, dieticians and other clinical experts.  They were given tailored advice about healthy eating and weight management during pregnancy, and were tested for diseases such as gestational diabetes.
Women who developed a complication could be treated in one visit, rather than being referred to a separate specialist clinic at a later date.
Around one in five pregnant women in the UK is obese and one in 50 is classed as severely obese.

University of Edinburgh
www.ed.ac.uk/news/2017/clinics-cut-pregnancy-risks-for-obese-women