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  Validation studies on the 5-hydroxy-L-[β-11C]-tryptophan/PET method for probing the decarboxylase step in serotonin synthesis

Lundquist, P., Blomquist, G., Hartvig, P., Hagberg, G., Torstenson, R., Hammarlund-Udenaes, M., et al. (2006). Validation studies on the 5-hydroxy-L-[β-11C]-tryptophan/PET method for probing the decarboxylase step in serotonin synthesis. Synapse, 59(8), 521-531. doi:10.1002/syn.20268.

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Lundquist, P, Author
Blomquist, G, Author
Hartvig, P, Author
Hagberg, GE1, Author              
Torstenson, R, Author
Hammarlund-Udenaes, M, Author
Långström, B, Author
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1External Organizations, ou_persistent22              

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 Abstract: The two-tissue compartment model, including irreversible trapping in the second compartment (2TCM) is used to describe the kinetics of 5-Hydroxy-L-[β-11C]-tryptophan ([11C]HTP), a radioligand used in positron emission tomography (PET) for probing the second enzymatic step in the biosynthesis of serotonin. In this study, we examined the capacity of the model to track pharmacological changes in this biological process. We also investigated the potential loss of [11C]HTP-derived radioactivity during a PET study, since loss should be negligible not to alter quantification. Six rhesus monkeys were investigated using bolus [11C]HTP/PET methodology before and after pharmacological intervention. The second enzymatic step in serotonin synthesis was inhibited using the aromatic L-amino acid decarboxylase inhibitor NSD1015 (10 mg/kg). The extent of [11C]-derived radioactivity loss from the brain was studied by inhibition of the enzyme responsible for formation of the tissue metabolite, monoamine oxidase A, using clorgyline (2 mg/kg). After NSD1015, the uptake of [11C]HTP-derived radioactivity was increased in all the investigated brain regions, while the parameter used to reflect decarboxylase activity, the net accumulation rate constant (Kacc), was decreased by 37% in the striatum, compared with baseline. Pretreatment with clorgyline did not change the brain uptake of [11C]HTP-derived radioactivity or Kacc. This study demonstrates that the 2TCM for [11C]HTP/PET is able to detect changes occurring during alteration of the biological process (i.e., the conversion of HTP to serotonin). Elimination of the radiotracer metabolite [11C]HIAA from the brain may be considered negligible if the PET study is limited to 60 min.

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 Dates: 2006-06
 Publication Status: Published in print
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 Identifiers: DOI: 10.1002/syn.20268
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Title: Synapse
Source Genre: Journal
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Publ. Info: New York, N.Y. : Wiley-Liss, Inc.
Pages: - Volume / Issue: 59 (8) Sequence Number: - Start / End Page: 521 - 531 Identifier: ISSN: 0887-4476
CoNE: https://pure.mpg.de/cone/journals/resource/954925553396