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

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with ¹¹C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: ¹¹C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, 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 following pretreatment with a clinical dose of the aromatase inhibitor letrozole (“blocking” studies). Time activity curves were obtained and standard uptake values (SUV) 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 all other organs, but was not blocked by pretreatment with letrozole. Mean SUVsmore » in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (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 all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced ¹¹C-vorozole uptake. Conclusions: PET with ¹¹C-vorozole is useful for assessing physiological 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.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [3] ;  [4]
  1. Stony Brook Univ., NY (United States). School of Medicine; Brookhaven National Lab. (BNL), Upton, NY (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States); State Univ. of New York (SUNY), Plattsburgh, NY (United States)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States)
  4. National Institute on Alcoholism and Alcohol Abuse, Bethesda, MD (United States)
  5. New York University Langone Medical Center, New York, NY (United States)
  6. Institut de Recerca Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Alta Tecnologia, Barcelona (Spain)
Publication Date:
OSTI Identifier:
1184517
Report Number(s):
BNL--108025-2015-JA
Journal ID: ISSN 0161-5505; R&D Project: MO-085; KP1602010; TRN: US1500519
Grant/Contract Number:
SC00112704
Type:
Accepted Manuscript
Journal Name:
Journal of Nuclear Medicine
Additional Journal Information:
Journal Volume: 56; Journal Issue: 4; Journal ID: ISSN 0161-5505
Publisher:
Society of Nuclear Medicine and Molecular Imaging
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY vorozole; aromatase inhibitors; PET; biodistribution; dosimetry; positron emission tomography (PET) facility