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Active Brown Adipose Tissue Protects Against ‘Pre-prediabetes’

In a prospective study of young, lean adults, PET/CT imaging revealed that higher levels of active brown adipose tissue (also known as brown fat) are more prevalent in individuals who exhibit very early indications of metabolic disorders. Published ahead of print in The Journal of Nuclear Medicine, the study suggests that active brown fat is recruited to counteract “pre-prediabetic” states, potentially serving as a first-line protective mechanism against very early metabolic or hormonal abnormalities.

Brown fat is a type of fat that is activated when a person gets cold, producing heat to warm the body. The presence of brown fat was initially recognized on oncologic FDG PET/CT scans, which are now the most commonly used technique for the in vivo detection of brown fat. Studies using PET with FDG and/or other fatty acid tracers have demonstrated that brown fat consumes glucose and fatty acids, making it a potential target for the treatment of obesity and other metabolic disorders.

“The primary aim of this study was to assess if there are differences in baseline glucose, insulin, lipid, and other metabolite levels between subjects with varying amounts of brown fat,” says John P. Crandall, BS, clinical research coordinator at the Mallinckrodt Institute of Radiology at Washington University School of Medicine in St. Louis. “We also examined patient blood samples and lifestyles to assess their association with brown fat levels.”

Thirty-four healthy adult volunteers between the ages of 18 and 35 and with a body mass index (BMI) between 18 and 25 were enrolled in the study. Blood samples were taken, and lifestyle interviews were performed. To activate the brown fat, participants wore cooling suits to bring their body’s temperature to just above the shivering point. After two hours, subjects removed the cooling suits and were imaged with FDG PET/CT. Postcooling blood samples were also taken after removal of the cooling suits.

Activated brown fat was analyzed for each subject, and glucose, insulin, lipid, and other metabolite levels were correlated with the volume and intensity of the active brown fat. Using a median cutoff, participants were classified as having high brown fat levels or low brown fat levels.

A higher level of activated brown fat was associated with early metabolic dysfunction. Precooling glucose, insulin, thyroid-stimulating hormone, and triglyceride levels were significantly higher in the high brown fat group than the low brown fat group. In addition, a significant difference in BMI was found, with subjects with high brown fat levels having a higher BMI than subjects with low levels of brown fat. Those with low brown fat levels were more likely to report observing a controlled diet and exercising regularly.

“Our study suggests brown adipose tissue may considerably influence (and be influenced by) overall metabolic health. Molecular imaging with FDG remains the most useful, noninvasive method for studying brown fat in humans,” says Richard L. Wahl, MD, FACR, director of the Mallinckrodt Institute of Radiology and chair of the department of radiology at Washington University School of Medicine. “Our findings show that molecular imaging potentially may be useful for identifying patients who are at risk of developing metabolic disorders and suggests activation of brown fat is a metabolic coping mechanism in ‘pre-prediabetes.’ Further studies in larger populations are warranted to confirm and expand upon our findings.”

— Source: SNMMI


New Radionuclide Combination Therapy Safe and Effective in mCRPC Patients

A novel nuclear medicine combination therapy has been proven safe and effective in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). The therapy, which combines the newly FDA-approved radionuclide therapy 177Lu-PSMA-617 with a radiosensitizer known as idronoxil (NOX66), reduced prostate-specific antigen (PSA) levels by more than 50% in a significant number of patients, resulting in a median overall survival of 19.7 months. This research was published in the April issue of The Journal of Nuclear Medicine.

mCRPC is a lethal disease, with a five-year survival rate of only 30%. Treatment options are limited, and treatment resistance occurs frequently. Combination therapies, however, may overcome these resistance mechanisms and improve patient outcomes.

“NOX66 has shown potential as a radiation sensitizer in prostate cancer,” says Louise Emmett, MD, MBChB, FRACP, director of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney, Australia. “Our study was developed to determine if combining NOX66 with 177Lu-PSMA-617 could improve treatment response with minimal increase in toxicity for mCRPC patients.”

The study included 56 men with progressive mCRPC who were previously treated with chemotherapy and novel androgen signaling inhibitors, a type of hormonal therapy. Patients received up to six doses of 177Lu-PSMA-617 in combination with varying doses of NOX66. After a median follow-up of 21.8 months, 86% of patients saw a decline in PSA levels, and nearly two-thirds of them had a PSA level decline of more than 50%.

Researchers also analyzed clinical, blood-based, and molecular imaging markers as potential predictors of treatment response. PSMA tumor volume at baseline measured by molecular imaging was the strongest predictor of treatment response and overall survival; the study found that men with higher tumor volumes responded poorly to treatment. Duration of treatment with androgen signaling inhibitors (more than 12 months) was associated with improved overall survival.

Emmett notes that these results point to two issues: “First, we need to ensure that men receive treatment earlier, before they have high-volume disease, and second, we need to explore why men with high-volume disease respond to treatment poorly,” she says. “Do we need to personalize radionuclide dose based on disease volume to get better treatment responses in men with high-volume disease? Further research is needed. It is clear, however, that trials like this help us explore how to safely prolong treatment responses and help men live longer, better lives.”

— Source: SNMMI