Anat Biegon, PhD, Professor of Neurology, Stony Brook University School of Medicine, was the first and corresponding (lead) author of an article published in the April issue of the Journal of Nuclear Medicine about a new, noninvasive nuclear medicine test that can be used to determine whether aromatase inhibitor treatment will be effective for specific patients with cancer.
The research, titled Aromatase Imaging with [N-Methyl-11C] Vorozole PET in Healthy Men and Women, shows that a PET scan with the ligand C-11-vorozole reliably detects aromatase in all body organs — demonstrating the value of its future use to pre-determine the effectiveness of the treatment for patients with breast, ovarian, endometrial and lung cancer, potentially reducing unnecessary treatment costs and adverse effects.
Aromatase inhibitors are drugs that work by blocking the aromatase enzyme, which turns the androgen hormone into cancer-stimulating estrogen. They are widely used in the adjuvant treatment of breast cancer and other endocrine conditions. However, no quantitative, noninvasive studies had been done on the distribution and regulation of aromatase in living humans.
“This is the first study conducted in living human subjects that surveys the whole body, comparing healthy young and old men and women,” said Dr. Biegon.
For the study, 13 men and 20 women were injected intravenously with C-11-vorozole (111–296 MBq/subject), with PET data acquired over a 90-minute period. Each subject had four scans, two per day separated by two to six weeks. Brain and torso or pelvic scans were included.
Young women were scanned at two discrete phases of the menstrual cycle (mid-cycle and late luteal). Men and postmenopausal women were also scanned after pretreatment with a clinical dose of the aromatase inhibitor letrozole. Time-activity curves were obtained, and standardized uptake values (SUV) were calculated for major organs, including brain, heart, lungs, liver, kidneys, spleen, muscle, bone, and male and female reproductive organs. Organ and whole-body radiation exposures were calculated using OLINDA software.
The study shows for the first time that the body organ with the largest stable capacity for estrogen biosynthesis is the male brain, closely followed by the female brain. Aromatase availability is slightly but consistently higher in all organs in men relative to women, with the exception of the ovary.
In addition, aromatase availability in the ovary is tightly linked to the ovulatory phase of the menstrual cycle in young women, with increased levels evident in one ovary/cycle around the time of ovulation. Also of interest is the finding that aging and cigarette smoke reduce aromatase availability in the brains of healthy men and women.
Dr. Biegon points out the significance of the study: “Research using in vitro methods indicates aromatase over expression is not limited to breast cancer and is evident in a considerable proportion of ovarian, endometrial and lung tumors. This study provides methodological, baseline and dosimetry information supporting the use of PET and C-11-vorozole in the noninvasive identification of individuals with disparate disorders who may benefit from treatment with aromatase inhibitors.
“It also offers the ability to distinguish patients with breast cancer who are not likely to benefit from this treatment, reducing unnecessary treatment costs and adverse effects. Finally, aromatase imaging can be used in monitoring efficacy of treatment with aromatase inhibitors and aid in the development of new drugs in this class.”
Another key finding relates to the differences between men and women.
“Radiotracer uptake and the resultant radiation exposure can be sex-dependent and strongly modulated by hormonal status,” Dr. Biegon said. “Nuclear medicine procedures need to be adjusted for these factors when applied in women.”
Congratulations, Anat, and thanks for your contributions to this important area of research.
Anat Biegon, PhD
Professor of Neurology
Stony Brook University School of Medicine