Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women.

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [11C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women. A subsample of 27 also completed personality measures to examine the relationship between aromatase and personality traits related to self-regulation and inhibitory control. Results indicated that aromatase availability in the amygdala was negatively associated with body mass index (BMI) (in kilograms per square meter) and positively correlated with scores of the personality trait constraint independent of sex or age. Individual variations in the brain's capacity to synthesize estrogen may influence the risk of obesity and self-control in men and women.

Aromatase imaging with [N-methyl-11C]vorozole PET in healthy men and women.

UNLABELLED: Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aimed to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathologic situations can be studied. METHODS: (11)C-vorozole (111-296 MBq/subject) was injected intravenously in 13 men and 20 women (age range, 23-67 y). PET data were acquired over a 90-min period. Each subject had 4 scans, 2 per day separated by 2-6 wk, including brain and torso or pelvis scans. Young women were scanned at 2 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 (penis, testes, uterus, ovaries). Organ and whole-body radiation exposures were calculated using OLINDA software. RESULTS: Liver uptake was higher than uptake in any other organ but was not blocked by pretreatment with letrozole. Mean SUVs were higher in men than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than SUVs in any other organ (ranging from 0.48 ± 0.05 in lungs to 1.5 ± 0.13 in kidneys). Mean ovarian SUVs (3.08 ± 0.7) were comparable to brain levels and higher than in any other organ. Furthermore, ovarian SUVs in young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, whereas aging and cigarette smoking reduced (11)C-vorozole uptake. CONCLUSION: PET with (11)C-vorozole is useful for assessing physiologic changes in estrogen synthesis capacity in the human body. Baseline levels in breasts, lungs, and bones are low, supporting further investigation of this tracer as a new tool for detection of aromatase-overexpressing primary tumors or metastases in these organs and optimization of treatment in cancer and other disorders in which aromatase inhibitors are useful.

PET imaging of thin objects: measuring the effects of positron range and partial-volume averaging in the leaf of Nicotiana tabacum.

INTRODUCTION: PET imaging in plants is receiving increased interest as a new strategy to measure plant responses to environmental stimuli and as a tool for phenotyping genetically engineered plants. PET imaging in plants, however, poses new challenges. In particular, the leaves of most plants are so thin that a large fraction of positrons emitted from PET isotopes ((18)F, (11)C, (13)N) escape while even state-of-the-art PET cameras have significant partial-volume errors for such thin objects. Although these limitations are acknowledged by researchers, little data have been published on them. METHODS: Here we measured the magnitude and distribution of escaping positrons from the leaf of Nicotiana tabacum for the radionuclides (18)F, (11)C and (13)N using a commercial small-animal PET scanner. Imaging results were compared to radionuclide concentrations measured from dissection and counting and to a Monte Carlo simulation using GATE (Geant4 Application for Tomographic Emission). RESULTS: Simulated and experimentally determined escape fractions were consistent. The fractions of positrons (mean±S.D.) escaping the leaf parenchyma were measured to be 59±1.1%, 64±4.4% and 67±1.9% for (18)F, (11)C and (13)N, respectively. Escape fractions were lower in thicker leaf areas like the midrib. Partial-volume averaging underestimated activity concentrations in the leaf blade by a factor of 10 to 15. CONCLUSIONS: The foregoing effects combine to yield PET images whose contrast does not reflect the actual activity concentrations. These errors can be largely corrected by integrating activity along the PET axis perpendicular to the leaf surface, including detection of escaped positrons, and calculating concentration using a measured leaf thickness.

Serial microPET measures of the metabolic reaction to a microdialysis probe implant.

Despite the widespread use of chronic brain implants in experimental and clinical settings, the effects of these long-term procedures on brain metabolism and receptor expression remain largely unknown. Under the hypothesis that intracerebral microdialysis transiently alters tissue metabolism, we performed a series of 18FDG microPET scans prior to and following surgical implantation of microdialysis cannulae. Parallel microPET measures using the competitive dopamine (DA) D2 receptor antagonist, 11C-raclopride, provided an assay of DA stability in these same animals. 18FDG scans were performed prior to microdialysis cannulation and again at 2, 12, 24, 48, 120, 168, 360 and 500 h (0.2, 0.5, 1, 2, 5, 7, 15 and 25 days). Separate animals received a sham surgery and the control group had no surgical intervention. For the first 24 h (scans at 2, 12 and 24 h post-surgery) uptake was reduced in both hemispheres. However, by 48 h, contralateral uptake had returned to pre-surgical levels. The striking finding was that from 48 to 500 h, the microdialysis cannulation produced widespread ipsilateral reductions in 18FDG uptake that encompassed the entire hemisphere. Despite the extent and persistence of these reductions, 11C-raclopride binding and ECF DA concentrations remained stable.