Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT.
Striatal dopamine transporter (DAT) function was evaluated in rats by in vivo SPECT-MRI coregistration using the radioligand 2-beta-carbomethoxy-3-beta-(4-[123I]iodophenyl)tropane (beta-[123I]CIT). The reconstructed transaxial resolution of 3.5 mm full width at half-maximum and the system sensitivity of 0.081 c/s/kBq using a 2.0-mm pinhole collimator aperture provided adequate spatial detail and sufficient sensitivity for imaging striatal beta-[123I]CIT uptake. SPECT images, coregistered onto a MRI template, showed high accuracy in the coronal and transverse planes (maximum mismatch of 1.3 mm). Following estimation of the in vivo binding equilibrium of beta-[123I]CIT in the healthy rat striatum, we evaluated the 6-hydroxydopamine-induced loss of striatal DAT function using beta-[123I]CIT SPECT and MRI coregistration and correlated these findings with dopaminergic cell counts in the substantia nigra pars compacta using TH immunohistochemistry. A subtotal unilateral DAT deficit was detected by beta-[123I]CIT SPECT in all animals which correlated significantly with the cell counting of the remaining dopaminergic neurons. beta-[123I]CIT pinhole SPECT provides a powerful and widely available tool for in vivo investigations of rat striatal DAT function. In contrast to classical autoradiography, the present method will be helpful in imaging dynamic changes of neurotransmission in the CNS by virtue of serial study designs. Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique.
Scherfler
Christoph
C
Department of Neurology, The Leopold-Franzens University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Donnemiller
Eveline
E
Schocke
Michael
M
Dierkes
Katja
K
Decristoforo
Clemens
C
Oberladstätter
Michael
M
Kolbitsch
Christian
C
Zschiegner
Fritz
F
Riccabona
Georg
G
Poewe
Werner
W
Wenning
Gregor
G
D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000031:analogs & derivatives*; D050483:Dopamine Plasma Membrane Transport Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D008474:Medial Forebrain Bundle; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008845:Microinjections; D008953:Models, Anatomic; D017072:Neostriatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493216:Slc6a3 protein, rat; D013565:Sympatholytics; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine