+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Identification and regional distribution in rat brain of radiometabolites of the dopamine transporter PET radioligand [11C]PE2I

, : Identification and regional distribution in rat brain of radiometabolites of the dopamine transporter PET radioligand [11C]PE2I. European Journal of Nuclear Medicine and Molecular Imaging 34(5): 667-678

We aimed to determine the composition of radioactivity in rat brain after intravenous administration of the dopamine transporter radioligand, [(11)C]PE2I. PET time-activity curves (TACs) and regional brain distribution ex vivo were measured using no-carrier-added [(11)C]PE2I. Carrier-added [(11)C]PE2I was administered to identify metabolites with high-performance liquid radiochromatography (RC) or RC with mass spectrometry (LC-MS and MS-MS). The stability of [(11)C]PE2I was assessed in rat brain homogenates. After peak brain uptake of no-carrier-added [(11)C]PE2I, there was differential washout rate from striata and cerebellum. Thirty minutes after injection, [(11)C]PE2I represented 10.9 +/- 2.9% of the radioactivity in plasma, 67.1 +/- 11.0% in cerebellum, and 92.5 +/- 3.2% in striata, and was accompanied by two less lipophilic radiometabolites. [(11)C]PE2I was stable in rat brain homogenate for at least 1 h at 37 degrees C. LC-MS identified hydroxylated PE2I (1) (m/z 442) and carboxyl-desmethyl-PE2I (2) (m/z 456) in brain. MS-MS of 1 gave an m/z 442-->424 transition due to H(2)O elimination, so verifying the presence of a benzyl alcohol group. Metabolite 2 was the benzoic acid derivative. Ratios of ex vivo measurements of [(11)C]PE2I, [(11)C]1, and [(11)C]2 in striata to their cognates in cerebellum were 6.1 +/- 3.4, 3.7 +/- 2.2 and 1.33 +/- 0.38, respectively, showing binding selectivity of metabolite [(11)C]1 to striata. Radiometabolites [(11)C]1 and [(11)C]2 were characterized as the 4-hydroxymethyl and 4-carboxyl analogs of [(11)C]PE2I, respectively. The presence of the pharmacologically active [(11)C]1 and the inactive [(11)C]2 is a serious impediment to successful biomathematical analysis.


PMID: 17096093

DOI: 10.1007/s00259-006-0277-1

Other references

Hikishima, K.; Ando, K.; Komaki, Y.; Kawai, K.; Yano, R.; Inoue, T.; Itoh, T.; Yamada, M.; Momoshima, S.; Okano, H.J.; Okano, H., 2016: Voxel-based morphometry of the marmoset brain: In vivo detection of volume loss in the substantia nigra of the MPTP-treated Parkinson's disease model. Movement dysfunction in Parkinson's disease (PD) is caused by the degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Here, we established a method for voxel-based morphometry (VBM) and automatic tissue segmentation of the...

Martin, D.-L.P.stan, M.; Lucas, P.; Gress, R.; Tarleton, R., L., 2007: TGF-o regulates pathology but not tissue CD8 T cell dysfunction during experimental Trypanosoma cruzi infection. Infection with the protozoan parasite Trypanosoma cruzi leads to chronic infection, with parasite persistence primarily in muscle tissue. CD8 T cells isolated from muscle tissue of T. cruzi-infected mice display decreased production of IFN-d in re...

Späth-Schwalbe, E.; Milz-Trendel, C.; Lisson, G.; Meinck, H.M.; Fehm, H.L., 1988: Addison disease with neurologic salience: an adrenomyeloneuropathic variant of adrenoleukodystrophy in a young male. Medizinische Klinik 83(11): 373-5, 390

Cavailloles, F.; Alperovitch, A.; Soussana, C.; Thebault, B.; Bok, B., 1980: Clinical usefulness of brain scintigrams. The records of 522 patients were reviewed and were classified clinically, according to the diagnosis and with respect to the scintigraphic result. The predictive value of scintigraphy is higher than that from the case history. If the clinical susp...

Wang, G.J.; Volkow, N.D.; Telang, F.; Jayne, M.; Fowler, J.S.; Ma, Y.; Rao, M.; Zhu, W.; Wong, C.; Pappas, N.; Geliebter, A., 2003: Motivation for food and orbitofrontal cortex activation during food presentation. Journal of Nuclear Medicine 44(5 Supplement): 246P-247P, May

Jedrzejewski, W.; Jedrzejewska, B.; Szymura, L., 1995: Weasel population response, home range, and predation on rodents in a deciduous forest in Poland. Numerical responses of the weasel Mustela nivalis to the changes in population density of forest rodents (bank vole Clethrionomys glareolus and yellow-necked mouse Apodemus flavicollis) and predation by weasels were studied in the pristine deciduo...

Bedair, H.; Liu, T.Thomas.; Kaar, J.L.; Badlani, S.; Russell, A.J.; Li, Y.; Huard, J., 2007: Matrix metalloproteinase-1 therapy improves muscle healing. Muscle undergoes time-dependent phases of healing after injury, which ultimately results in residual fibrosis in the injured area. The use of exogenous matrix metalloproteinases (MMPs) may improve recovery after muscle injury by promoting the dig...

Aon, M.A.; Cortassa, S.; Akar, F.G.; Brown, D.A.; Zhou, L.; O'Rourke, B., 2009: From mitochondrial dynamics to arrhythmias. The reactive oxygen species (ROS)-dependent mitochondrial oscillator described in cardiac cells exhibits at least two modes of function under physiological conditions or in response to metabolic and oxidative stress. Both modes depend upon network...

Mustra, D.J.; Warren, A.J.; Hamilton, J.W., 1999: Interaction of the DNA binding domain of the repair protein XPA with a mitomycin C-DNA interstrand crosslink. Proceedings of the American Association for Cancer Research Annual Meeting 40: 155, March

Takahashi, H.; Iwanaga, S.; Kitagawa, T.; Hokama, Y.; Suzuki, T., 1974: Snake venom proteinase inhibitors. II. Chemical structure of inhibitor II isolated from the venom of Russell's viper (Vipera russelli). Journal of Biochemistry 76(4): 721-733