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Nuklearmedizin 2003; 42(01): 4-9
DOI: 10.1055/s-0038-1623898
Original Article
Schattauer GmbH

Radioligands for imaging myocardial α- and β-adrenoceptors[*]

Radioliganden für die Bildgebung kardialer α- und β-Adrenozeptoren
B. Riemann
1   Department of Nuclear Medicine (Head: Prof. Dr. Dr. O. Schober)
,
M. Schäfers
1   Department of Nuclear Medicine (Head: Prof. Dr. Dr. O. Schober)
,
M. P. Law
2   MRC Clinical Sciences Centre, Imperial College School of Science, Technology and Medicine (Head: Prof. Dr. P. G. Camici) Hammersmith Hospital, London, UK
,
T. Wichter
3   Cardiology and Angiology (Head: Prof. Dr. G. Breithardt), Münster University, Germany
,
O. Schober
1   Department of Nuclear Medicine (Head: Prof. Dr. Dr. O. Schober)
› Author Affiliations
Further Information

Publication History

Received: 02 December 2002

05 December 2002

Publication Date:
10 January 2018 (online)

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Summary

Alpha- and beta-adrenoceptors play an important role in the control of heart function. According to their molecular, biological, and pharmacological characteristics, they are subdivided into α1-, α2- and β1-, β2-, β3-, β4-adrenoceptors. In cardiac disease, there is often a selective downregulation of β1-adrenoceptors associated with a relative increase in β2- and α1-adrenoceptors. Functional imaging techniques like single-photon emission tomography (SPECT) and positron emission tomography (PET) provide the unique capability for non-invasive assessment of cardiac adrenoceptors. Radioligands with high specific binding to cardiac α- and β-adrenoceptors suitable for radiolabelling are required for clinical studies. The non-selective β-adrenoceptor antagonist [11C]CGP-12177 was used to quantify β-adrenoceptor density using PET in patients with heart disease. New non-selective ligands (e. g. [11C]CGP-12388, [18F]CGP-12388, [11C]carazolol and [18F]fluorocarazolol) are currently evaluated; β1-selective radioligands (e. g. [11C]CGP-26505, [11C]bisoprolol, [11C]HX-CH 44) and β2-selective radioligands (e. g. [11C]formoterol, [11C]ICI-118551) were assessed in animals. None of them turned out as suitable for cardiac PET.

Potential radioligands for imaging cardiac α1-adrenoceptors are based on prazosin. Whereas [11C]prazosin shows low specific binding to myocardium, its derivative [11C]GB67 looks more promising. The putative α2-adrenoceptor radioligand [11C]MK-912 shows high uptake in rodent myocardium but has not yet been evaluated in man.

A number of radioligands were evaluated for assessing cardiac adrenoceptors using PET. New radioligands are needed to provide more insight into cardiac pathophysiology which may influence the therapeutic management of patients with cardiovascular disease.

Zusammenfassung

Alpha- und beta-Adrenozeptoren spielen eine wichtige Rolle für die Herzfunktion. Nach ihren molekularen, biologischen und pharmakologischen Eigenschaften werden sie in α1-, α2- und β1-, β2-, β3-, β4-Adrenozeptoren eingeteilt. Kardiale Erkrankungen sind häufig durch eine selektive Down-Regulation der β1-Adrenozeptoren gekennzeichnet, die mit relativer Zunahme der β2- und α1-Adrenozeptoren einhergeht. Die funktionellen bildgebenden Verfahren Einzel-Photonen-Emissionstomographie (SPECT) und Positronenemissionstomographie (PET) ermöglichen es, kardiale Adrenozeptoren nicht invasiv zu untersuchen. Für klinische Studien müssen dazu geeignete Radioliganden entwickelt werden, die mit hoher Spezifität an kardiale α- bzw. β-Adrenozeptoren binden und die radioaktiv markiert werden können.

Der nicht selektive β-Adrenozeptorantagonist [11C]CGP-12177 wurde erfolgreich zur Quantifizierung der β-Adrenozeptordichte mittels PET bei herzkranken Patienten eingesetzt. Neue nicht selektive Radioliganden (z.B. [11C]CGP-12388, [18F]CGP-12388, [11C]Carazolol, [18F]Fluorcarazolol) werden zurzeit evaluiert. Einige β1-selektive (z.B. [11C]CGP-26505, [11C]Bisoprolol, [11C]HX-CH 44) und β2-selektive Radioliganden ([11C]Formoterol, [11C]ICI-118551) wurden im Tierversuch erprobt, doch als Tracer für das Herz-PET waren sie ungeeignet.

Zur Darstellung der kardialen α1-Adrenozeptoren wurden geeignete Radioliganden basierend auf Prazosin entwickelt. Während [11C]Prazosin nur eine geringe spezifische Bindung im Herzen zeigte, scheint dessen Derivat [11C]GB67 verheißungsvoll zu sein. Der 11C-markierte α2-Adrenozeptorantagonist [11C]MK-912 zeigte eine hohe myokardiale Aufnahme bei Nagern, wurde aber am Menschen noch nicht untersucht.

Bisher wurde eine Reihe von Radioliganden zur Darstellung der kardialen Adrenozeptoren mittels PET untersucht. Weitere Liganden sollten entwickelt werden mit dem Ziel, Einblicke in die Pathophysiologie kardialer Erkrankungen zu erlangen, die das therapeutische Vorgehen bei Patienten mit kardiovaskulären Erkrankungen beeinflussen könnten.

Keywords

Adrenoceptors - myocardium - PET

Schlüsselwörter

Adrenozeptoren - Myokard - PET

* Diese Arbeit ist Prof. Dr. Dr. h. c. Heinz Hundeshagen zum 75. Geburtstag gewidmet.


 

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