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Increase in hypothalamic [11C]vorozole binding to aromatae in macaque monkeys treated with anabolic androgenic steroids: A PET study
Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
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Manuskript (Övrigt vetenskapligt)
Identifikatorer
URN: urn:nbn:se:uu:diva-97479OAI: oai:DiVA.org:uu-97479DiVA, id: diva2:172446
Tillgänglig från: 2008-09-08 Skapad: 2008-09-08 Senast uppdaterad: 2010-01-13Bibliografiskt granskad
Ingår i avhandling
1. Imaging brain aromatase by using PET: A way to study anabolic steroid abuse
Öppna denna publikation i ny flik eller fönster >>Imaging brain aromatase by using PET: A way to study anabolic steroid abuse
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Aromatase is an enzyme that facilitates the conversion of androgens to estrogens and may play a role in mood and mental status. The main theme of this thesis is the imaging of brain aromatase by use of the PET technique. The PET tracer for aromatase, 11C-labeled vorozole (VOZ) was developed and evaluated by with in vitro and in vivo methods. In vitro experiments using rat brain showed that VOZ was distributed in the medial amygdala, bed nucleus of the stria terminalis and medial preoptic area, regions of the brain known to be rich in aromatase and the KD value was determined to be 0.60 nM. The in vivo PET study in rhesus monkey brain revealed that VOZ penetrated the blood-brain barrier and accumulated in the amygdala and hypothalamus. Taken together, VOZ is a good PET tracer for in vivo aromatase imaging with high affinity and high sensitivity.

This technique was applied to an investigation of brain aromatase under the physiological conditions simulating anabolic-androgenic steroid abuse. A significant increase in VOZ binding by anabolic-androgenic steroids was observed in the bed nucleus of stria terminalis and medial preoptic area in the rat brain. In contrast, no significant change in binding was observed in the medial amygdala. These results indicate that the manner of regulation of aromatase expression might be different in the bed nucleus of stria terminalis and medial preoptic area compared with that in the medial amygdala. The aromatase expression was suggested to be regulated through androgen receptors, as indicated in a study with flutamide treatment. The increased aromatase expression was seen in neurons. The PET study with anabolic steroid-treated rhesus monkeys also showed increased VOZ binding in the hypothalamus but not in the amygdala. The alteration of density of aromatase binding in the hypothalamic area could explain some psychological features of anabolic-androgenic steroid abusers.

Novel PET tracers for aromatase were developed and examined. The two newly synthesized 18F-labeled vorozole analogs, [18F]FVOZ and [18F]FVOO, displayed different characteristics. Both tracers showed similar binding pattern as VOZ; however, [18F]FVOO was metabolized very quickly, meaning that this tracer is not suitable as a PET tracer. On the other hand, [18F]FVOZ can be an appropriate PET tracer.

The role of aromatase in the human brain has not been clarified yet. To approach this problem by in vivo methods, we have just started PET studies to explore aromatase expression in humans.

Ort, förlag, år, upplaga, sidor
Uppsala: Universitetsbiblioteket, 2008. s. 63
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 370
Nyckelord
aromatase, brain, molecular imaging, PET, [11C]Vorozole, amygdala, hypothalamus, anabolic-androgenic steroids, abuse, [18F]Vorozole analogs
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
urn:nbn:se:uu:diva-9234 (URN)978-91-554-7266-5 (ISBN)
Disputation
2008-10-04, B42, A4, BMC, Uppsala, 09:15
Opponent
Handledare
Tillgänglig från: 2008-09-08 Skapad: 2008-09-08 Senast uppdaterad: 2022-03-11Bibliografiskt granskad

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