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 of the distribution and regulation of aromatase in living humans.
Anat Biegon, PhD, corresponding author of the study, explains, “This is the first study conducted in living human subjects that surveys the whole body, comparing healthy young and old men and women.”
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 (midcycle 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.
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 non-invasive identification of individuals with disparate disorders who may benefit from treatment with aromatase inhibitors.” She notes, “It also offers the ability to distinguish breast cancer patients 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. Dr. Biegon states, “Radiotracer uptake and the resultant radiation exposure can be sex-dependent and strongly modulated by hormonal status. Nuclear medicine procedures need to be adjusted for these factors when applied in women.”
Biegon et al. Aromatase Imaging with [N-Methyl-11C] Vorozole PET in Healthy Men and Women. J Nucl Med. 2015;56:580-585 EPub ahead of print. doi: 10.2967/jnumed.114.150383 [Abstract]