New Radiotracer Can Identify Nearly 30 Types of Cancer

A novel class of radiopharmaceuticals has proven effective in non-invasively identifying nearly 30 types of malignant tumors, according to research published in the June issue of The Journal of Nuclear Medicine. Using 68Ga-FAPI positron emission tomography/computed tomography (PET/CT), researchers were able to image a wide variety of tumors with very high uptake and image contrast, paving the way for new applications in tumor characterization, staging and therapy.

The 68Ga-FAPI radiotracer targets cancer-associated fibroblasts, which can contribute up to 90 percent of a tumor’s mass. Many cancer-associated fibroblasts differ from normal fibroblasts by their specific expression of the fibroblast activation protein, or FAP. FAP-specific inhibitors were first developed as conventional anticancer drugs; now they have been advanced into tumor-targeting radiopharmaceuticals.

In the retrospective study, researchers used PET/CT to image 80 patients with 28 different kinds of cancer, aiming to quantify 68Ga-FAPI uptake in primary, metastatic or recurring cancers. All patients were referred for experimental diagnostics by their treating oncologists because they were facing an unmet diagnostic challenge that could not be solved sufficiently with standard methods. The injected activity for the 68Ga-FAPI examinations was 122-312 MBq, and the PET scans were initiated one hour after injection. Tumor tracer uptake was measured by SUVmean and SUVmax.

All patients tolerated the examination well. As the overall SUV mean, median and range of 68Ga-FAPI in primary tumors and metastatic lesions did not differ significantly, researchers analyzed all results in one group.

The highest average SUVmax (SUVmax >12) was found in sarcoma, esophageal, breast, cholangiocarcinoma and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax <6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic and gastric cancers. The average SUVmax of hepatocellular, colorectal, head-neck, ovarian, pancreatic and prostate cancer was intermediate (SUVmax 6-12). In addition, the tumor-to-background ratios were more than three-fold in the intermediate group and more than six-fold in the high-intensity uptake group, resulting in high image contrast and excellent tumor delineation.

“The remarkably high uptake of 68Ga-FAPI makes it useful for many cancer types, especially in cases where traditional 18F-FDG PET/CT faces limitations,” said Uwe Haberkorn, MD, professor of nuclear medicine at the University Hospital of Heidelberg and the German Cancer Research Center in Heidelberg, Germany. “For example, low-grade sarcomas generally have a low uptake of 18F-FDG, causing an overlap between benign and malignant lesions. In breast cancer, 18F-FDG PET/CT is commonly used in recurrence, but not generally recommended for initial staging. And for esophageal cancer, 18F-FDG PET/CT often has only a low to moderate sensitivity for lymph node staging.”

In contrast to 18F-FDG PET/CT, 68Ga-FAPI PET/CT can be performed without specific patient preparation such as fasting or recline during uptake time. This is a potential operational advantage for 68Ga-FAPI PET/CT, as it stands to improve patient comfort and accelerate work-flow.

According to Haberkorn, 68Ga-FAPI offers the possibility of a theranostic approach in the future. “Cancer associated fibroblasts have been described as immunosuppressive and as conferring resistance to chemotherapy, which makes them attractive targets for combination therapies,” he said. “Because the 68Ga-FAPI tracers contain the universal DOTA-chelator, it is possible to label them with therapeutic radionuclides whose half-life fits to the tumor retention time of the carrier molecule. Since the tracer has been observed to accumulate in several important tumor entities, there may be a huge field of therapeutic application to be evaluated in the future.”

Source: Society of Nuclear Medicine and Molecular Imaging


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New Review Identifies Four Hallmarks of Cancer Metastasis

Adam Pope wrote . . . . . . . . .

Researchers at the University of Alabama at Birmingham and the University of Kansas Cancer Center have identified four hallmarks of cancer metastasis — when cancer has spread to different parts of the body from where it started. Metastasis is believed to be the cause of up to 90 percent of cancer deaths.

Douglas Hurst, Ph.D., assistant professor in the UAB Department of Pathology, and Danny Welch, Ph.D., associate director of Education at the KUCC, conducted a literature review of more than 10,000 publications on metastasis, and published their findings in Cancer Research, from the American Association for Cancer Research.

Metastasis can be very difficult to treat. Virtually any cancer type can form metastatic tumors. The most common sites for cancers to metastasize include the brain, bones, lungs and liver. Other areas include the adrenal gland, lymph nodes, skin and other organs.

By defining the unique properties of metastatic cancer cells, Hurst says, he hopes to provide a conceptual framework to accelerate the discovery of treatment strategies.

“Our attempts to identify the underlying first principles of the metastatic process hopefully provide a means for simplifying the processes that are essential for all metastases to develop,” the authors said in the review.

Hurst and Welch identified four hallmarks of metastasis:

  1. Motility and invasion
  2. Modulation of the microenvironment
  3. Plasticity
  4. Ability to colonize

Defining the hallmarks of metastasis has been complicated by both heterogeneity among tumor cells, and the myriad interactions with other molecules and cells throughout the process, according to the authors.

Hurst and Welch say they hope that refining definitions and bringing together diverse data will identify vulnerabilities that metastasis researchers can exploit in the quest to treat cancer metastasis.

Hurst, who also serves as an associate scientist at the O’Neal Comprehensive Cancer Center at UAB, explains why metastasis is hard to understand.

“Metastasis is a highly complex pathological process,” Hurst said. “Increased specificity in defining the underlying principles is important to better understand and interpret the literature to move forward in the development of therapeutic interventions.”

Source: University of Alabama at Birmingham


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More Proof High-Fiber Diets Help Prevent Cancers, Heart Disease

Alan Mozes wrote . . . . . . . . .

A large, new analysis helps confirm that eating lots of grains, vegetables and fruit lowers your risk of dying early from cancer or heart disease.

When compared with those who consume very little fiber, people at the high end of the fiber-eating spectrum saw their risk for dying from heart disease, stroke, type 2 diabetes and/or colon cancer plummet by 16 to 24 percent, investigators reported.

The team also concluded that more is definitely more: For every additional 8 grams of dietary fiber a person consumes, the risk for each of those illnesses was found to fall by another 5 to 27 percent.

“The health benefits of fiber are supported by over 100 years of research into its chemistry, physical properties, physiology and effects on metabolism,” said study author Andrew Reynolds, a postdoctoral research fellow at the University of Otago in New Zealand.

“What really surprised us was the range of conditions that higher intakes of dietary fiber seemed to improve,” Reynolds added. “Heart disease, type 2 diabetes and [colon] cancers are some of the most detrimental diseases of our time.”

The conclusions follow a deep-dive into the results of 185 observational studies conducted over the last four decades, alongside the findings of another 58 clinical trials involving more than 4,600 participants.

Reynolds and his colleagues reported their work, which was commissioned by the World Health Organization, in the Jan. 10 online edition of The Lancet.

The research team noted that worldwide most people eat less than 20 grams of fiber each day, a figure that dips to just 15 grams per day among Americans. For examples of foods: 1 slice of whole wheat bread has 2 grams of fiber; 1 cup of boiled broccoli has 5 grams; 1 medium orange has 3 grams, and 1 cup of cooked black beans has 15 grams.

But investigators found that taking in 25 to 29 grams of dietary fiber per day is just an “adequate” starting point, with greater protection against premature death accruing more heartily to those who routinely consume even greater amounts of fiber.

For example, every additional 15-gram bump in daily whole grain intake was found to curtail an individual’s overall risk of early death — as well as their risk of early death from heart disease — by between 2 and 19 percent.

What’s more, the researchers found little evidence that eating more dietary fiber was in any way risky.

And even for those whose diets have for years largely sidestepped fiber, Reynolds suggested it’s never too late to start embracing fiber’s benefits.

“We saw this from the trials where participants were asked to increase their fiber intakes,” he said. “When considering all the trials of increasing fiber intakes, those participants that did reduced both their body weight and the total cholesterol in their blood, two important predictors of disease.”

That thought was seconded by Dr. Gerald Bernstein, program coordinator for the Friedman Diabetes Institute at Lenox Hill Hospital in New York City.

“I do not think there is a time to start that is not beneficial,” he said. “Of course, combined with some exercise and calorie control the benefits become exponential.”

As to the New Zealand study results, Bernstein observed that “none of this is surprising.” But he suggested that the findings “should lead to a change in dietary recommendations.”

That thought was seconded by Lona Sandon, program director and associate professor in the department of clinical nutrition for the school of health professions at the University of Texas Southwestern Medical Center at Dallas.

“This is just one more that supports and further solidifies the recommendations registered dietitian nutritionists have been making for years,” said Sandon.

“It’s never too late to start on a healthy diet,” she said. “Sure, you may have missed out on some health prevention years and therefore your risk will not be as low as someone who has been eating whole grains all their life. But you have nothing to lose by giving a healthy diet a try.”

Source: HealthDay


Read also:

Fiber: It’s Not Just for Adults . . . . .

High intake of dietary fiber and whole grains associated with reduced risk of non-communicable diseases . . . . .


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Stop Adding Cancer-causing Chemicals to Our Bacon, Experts Tell UK Meat Industry

Jamie Doward wrote . . . . . . . . .

The reputation of the meat industry will sink to that of big tobacco unless it removes cancer-causing chemicals from processed products such as bacon and ham, a coalition of experts and politicians warn today.

Led by Professor Chris Elliott, the food scientist who ran the UK government’s investigation into the horse-meat scandal, and Dr Aseem Malhotra, a cardiologist, the coalition claims there is a “consensus of scientific opinion” that the nitrites used to cure meats produce carcinogens called nitrosamines when ingested.

It says there is evidence that consumption of processed meats containing these chemicals results in 6,600 bowel cancer cases every year in the UK – four times the fatalities on British roads – and is campaigning for the issue to be taken as seriously as sugar levels in food.

“Government action to remove nitrites from processed meats should not be far away,” Malhotra said. “Nor can a day of reckoning for those who dispute the incontrovertible facts. The meat industry must act fast, act now – or be condemned to a similar reputational blow to that dealt to tobacco.”

Other coalition members include Labour’s deputy leader, Tom Watson; former shadow environment secretaries Mary Creagh and Kerry McCarthy; the Tory chair of parliament’s cross-party group on food and health, David Amess; the Liberal Democrat vice-chair of Westminster’s cross-party children’s group, Joan Walmsley; nutritionist Dr Chris Gill; the Cancer Fund for Children, and John Procter MEP, who sits on the European parliament’s environment, public health and food safety committee.

In a statement issued today, the coalition warns “that not enough is being done to raise awareness of nitrites in our processed meat and their health risks, in stark contrast to warnings regularly issued regarding sugar and fattening foods”.

In 2015 the World Health Organisation published evidence that linked processed meats to 34,000 cases of colorectal cancer worldwide each year – and identified nitrites and nitrosamines as the likely cause.

Two studies published this year have also raised concerns. Glasgow University researchers collated data from 262,195 British women that suggested reducing processed meat consumption could cut a woman’s risk of developing breast cancer. And a Johns Hopkins University School of Medicine in the US study suggested a direct link between nitrites and the onset of mental health problems. Its 10-year analysis of more than 1,000 people found patients taken to hospital with manic episodes were three times more likely to have recently eaten nitrite-cured meat.

The coalition says the meat industry claims nitrites are essential to combat botulism and infection. But Malhotra said Parma ham producers have not used nitrites for 25 years.

Nitrites give cured products such as bacon and ham their attractive pink colour. Some companies are substituting these with natural alternatives. A year ago, Northern Irish company Finnebrogue launched the “first truly nitrite-free bacon”, with fruit and spice extracts. It is stocked by many major supermarkets. Ocado also sells nitrite-free streaky bacon fromNorthamptonshire-based Houghton Hams and a nitrite-free prosciutto from Unearthed.

Source: The Guardian

Researchers Develop Sensors to Detect and Measure Cancer’s Ability to Spread

Yadira Galindo wrote . . . . . . . . .

The spread of invasive cancer cells from a tumor’s original site to distant parts of the body is known as metastasis. It is the leading cause of death in people with cancer. In a paper published online in iScience, University of California San Diego School of Medicine researchers reported engineering sensors that can detect and measure the metastatic potential of single cancer cells.

“Cancer would not be so devastating if it did not metastasize,” said Pradipta Ghosh, MD, professor in the UC San Diego School of Medicine departments of Medicine and Cellular and Molecular Medicine, director of the Center for Network Medicine and senior study author.

“Although there are many ways to detect metastasis once it has occurred, there has been nothing available to ‘see’ or ‘measure’ the potential of a tumor cell to metastasize in the future. So at the Center for Network Medicine, we tackled this challenge by engineering biosensors designed to monitor not one, not two, but multiple signaling programs that drive tumor metastasis; upon sensing those signals a fluorescent signal would be turned on only when tumor cells acquired high potential to metastasize, and therefore turn deadly.”

Cancer cells alter normal cell communications by hijacking one of many signaling pathways to permit metastasis to occur. As the tumor cells adapt to the environment or cancer treatment, predicting which pathway will be used becomes difficult. By comparing proteins and protein modifications in normal versus all cancer tissues, Ghosh and colleagues identified a particular protein and its unique modification called tyrosine-phosphorylated CCDC88A (GIV/Girdin) that are only present in solid tumor cells. Comparative analyses indicated that this modification could represent a point of convergence of multiple signaling pathways commonly hijacked by tumor cells during metastasis.

The team used novel engineered biosensors and sophisticated microscopes to monitor the modification on GIV and found that, indeed, fluorescent signals reflected a tumor cell’s metastatic tendency. They were then able to measure the metastatic potential of single cancer cells and account for the unknowns of an evolving tumor biology through this activity. The result was the development of Fluorescence Resonance Energy Transfer (FRET) biosensors.

Although highly aggressive and adaptive, very few cancer cells metastasize and that metastatic potential comes and goes, said Ghosh. If metastasis can be predicted, this data could be used to personalize treatment to individual patients. For example, patients whose cancer is not predicted to metastasize or whose disease could be excised surgically might be spared from highly toxic therapies, said Ghosh. Patients whose cancer is predicted to spread aggressively might be treated with precision medicine to target the metastatic cells.

“It’s like looking at a Magic 8 Ball, but with a proper yardstick to measure the immeasurable and predict outcomes,” said Ghosh. “We have the potential not only to obtain information on single cell level, but also to see the plasticity of the process occurring in a single cell. This kind of imaging can be used when we are delivering treatment to see how individual cells are responding.”

The sensors need further refinement, wrote the authors, but have the potential to be a transformative advance for cancer cell biology.

Source: UC San Diego


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