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

Abstract

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]
+ Show Author Affiliations
  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:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
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
Resource 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
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

Citation Formats

Biegon, Anat, Fowler, Joanna S., Alexoff, David L., Kim, Sung Won, Logan, Jean, Pareto, Deborah, Schlyer, David, and Wang, Gene-Jack. Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women. United States: N. p., 2015. Web. doi:10.2967/jnumed.114.150383.
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Biegon, Anat, Fowler, Joanna S., Alexoff, David L., Kim, Sung Won, Logan, Jean, Pareto, Deborah, Schlyer, David, & Wang, Gene-Jack. Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women. United States. https://doi.org/10.2967/jnumed.114.150383
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Biegon, Anat, Fowler, Joanna S., Alexoff, David L., Kim, Sung Won, Logan, Jean, Pareto, Deborah, Schlyer, David, and Wang, Gene-Jack. Thu . "Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women". United States. https://doi.org/10.2967/jnumed.114.150383. https://www.osti.gov/servlets/purl/1184517.
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@article{osti_1184517,
title = {Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women},
author = {Biegon, Anat and Fowler, Joanna S. and Alexoff, David L. and Kim, Sung Won and Logan, Jean and Pareto, Deborah and Schlyer, David and Wang, Gene-Jack},
abstractNote = {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 SUVs 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.},
doi = {10.2967/jnumed.114.150383},
journal = {Journal of Nuclear Medicine},
number = 4,
volume = 56,
place = {United States},
year = {Thu Feb 19 00:00:00 EST 2015},
month = {Thu Feb 19 00:00:00 EST 2015}
}
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Works referenced in this record:

The Cytochrome P450 Superfamily: Biochemistry, Evolution and Drug Metabolism in Humans
journal, December 2002

Aromatase—A Brief Overview
journal, March 2002

Unique distribution of aromatase in the human brain: In vivo studies with PET and [N-methyl-11C]vorozole
journal, April 2010

  • Biegon, Anat; Kim, Sung Won; Alexoff, David L.
  • Synapse, Vol. 64, Issue 11
  • DOI: 10.1002/syn.20791

Regional Distribution of Aromatase in the Human Brain
book, October 2012

Regulation of Brain Aromatase Activity in Rats*
journal, January 1984

  • Roselli, Charles E.; Ellinwood, William E.; Resko, John A.
  • Endocrinology, Vol. 114, Issue 1
  • DOI: 10.1210/endo-114-1-192

Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain
journal, July 1994

Aromatase in the Brain: Not Just for Reproduction Anymore
journal, June 2008

Neuroprotective actions of brain aromatase
journal, July 2009

  • Saldanha, Colin J.; Duncan, Kelli A.; Walters, Bradley J.
  • Frontiers in Neuroendocrinology, Vol. 30, Issue 2
  • DOI: 10.1016/j.yfrne.2009.04.016

Aromatase Expression in Women’s Cancers
book, January 2008

New drugs in development for the treatment of endometriosis
journal, July 2008

  • Fedele, Luigi; Somigliana, Edgardo; Frontino, Giada
  • Expert Opinion on Investigational Drugs, Vol. 17, Issue 8
  • DOI: 10.1517/13543784.17.8.1187

Targeting Aromatase and Estrogen Signaling in Human Non-Small Cell Lung Cancer
journal, February 2009

  • Márquez-Garbán, Diana C.; Chen, Hsiao-Wang; Goodglick, Lee
  • Annals of the New York Academy of Sciences, Vol. 1155, Issue 1
  • DOI: 10.1111/j.1749-6632.2009.04116.x

Aromatase and Amphiregulin Are Correspondingly Expressed in Human Liver Cancer Cells
journal, February 2009

R 76713 and enantiomers: Selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis
journal, October 1990

Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole
journal, July 2006

Synthesis and PET studies of [11C-cyano]letrozole (Femara), an aromatase inhibitor drug
journal, February 2009

Reinvestigation of the synthesis and evaluation of [N-methyl-11C]vorozole, a radiotracer targeting cytochrome P450 aromatase
journal, April 2009

11 C-Cetrozole: An Improved C- 11 C-Methylated PET Probe for Aromatase Imaging in the Brain
journal, March 2014

  • Takahashi, Kayo; Hosoya, Takamitsu; Onoe, Kayo
  • Journal of Nuclear Medicine, Vol. 55, Issue 5
  • DOI: 10.2967/jnumed.113.131474

Plasma input function determination for PET using a commercial laboratory robot
journal, October 1995

Kinetic Analysis of [ 11 C]Vorozole Binding in the Human Brain with Positron Emission Tomography
journal, May 2014

Aromatase inhibitors in ovarian cancer: is there a role?
journal, July 2008

The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters
journal, September 2003

  • Bulun, Serdar E.; Sebastian, Siby; Takayama, Kazuto
  • The Journal of Steroid Biochemistry and Molecular Biology, Vol. 86, Issue 3-5
  • DOI: 10.1016/S0960-0760(03)00359-5

Physiological 18F-FDG uptake in the ovaries and uterus of healthy female volunteers
journal, December 2004

  • Nishizawa, Sadahiko; Inubushi, Masayuki; Okada, Hiroyuki
  • European Journal of Nuclear Medicine and Molecular Imaging, Vol. 32, Issue 5
  • DOI: 10.1007/s00259-004-1703-x

In Vivo Imaging of Brain Aromatase in Female Baboons: [ 11 C]Vorozole Kinetics and Effect of the Menstrual Cycle
journal, November 2013

Aromatase in the human central nervous system: Aromatase in human brain
journal, March 1998

Characterization of Aromatase Cytochrome P450 Activity in the Human Temporal Lobe
journal, August 1999

  • Steckelbroeck, S.
  • Journal of Clinical Endocrinology & Metabolism, Vol. 84, Issue 8
  • DOI: 10.1210/jc.84.8.2795

Expression of CYP19 (aromatase) mRNA in different areas of the human brain
journal, September 1999

  • Stoffel-Wagner, Birgit; Watzka, Matthias; Schramm, Johannes
  • The Journal of Steroid Biochemistry and Molecular Biology, Vol. 70, Issue 4-6
  • DOI: 10.1016/S0960-0760(99)00114-4

Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons
journal, April 2010

Three Different Promoters Control Expression of the Aromatase Cytochrome P450 Gene (Cyp19) in Mouse Gonads and Brain1
journal, March 2003

Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome
journal, July 2014

  • Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.
  • New England Journal of Medicine, Vol. 371, Issue 2
  • DOI: 10.1056/NEJMoa1313517
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    Works referencing / citing this record:

    Neuroimaging the Menstrual Cycle and Premenstrual Dysphoric Disorder
    journal, August 2015

    Association between aromatase in human brains and personality traits
    journal, November 2018

    Estradiol induces BDNF/TrkB signaling in triple-negative breast cancer to promote brain metastases
    journal, February 2019

    The deep biology of cognition: Moving toward a comprehensive neurodevelopmental model of Turner syndrome
    journal, February 2019

    • Knickmeyer, Rebecca C.; Hooper, Stephen R.
    • American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Vol. 181, Issue 1
    • DOI: 10.1002/ajmg.c.31679

    Sex steroid hormones and brain function: PET imaging as a tool for research
    journal, February 2018

    • Moraga-Amaro, R.; van Waarde, A.; Doorduin, J.
    • Journal of Neuroendocrinology, Vol. 30, Issue 2
    • DOI: 10.1111/jne.12565

    Estradiol induces BDNF/TrkB signaling in triple-negative breast cancer to promote brain metastases
    journal, February 2019

    Association between aromatase in human brains and personality traits
    journal, November 2018

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