Quantification of 123I-PE2I binding to dopamine transporter with SPECT after bolus and bolus/infusion.
The aim of the present study was to describe a method combining easy implementation in a clinical setting with accuracy and precision in quantification of 123I-labeled N-(3-iodoprop-(2E)-enyl)-2beta-carboxymethoxy-3beta-(4'-methylphenyl)nortropane (PE2I) binding to brain dopamine transporter.


METHODS
Five healthy subjects (mean age, 50 y; range, 40-68 y) were studied twice. In the first experiment, dynamic SPECT data and arterial plasma input curves obtained after 123I-PE2I bolus injection were assessed using Logan, kinetic, transient equilibrium, and peak equilibrium analyses. Accurate and precise determination of BP1 (binding potential times the free fraction in the metabolite-corrected plasma compartment) and BP2 (binding potential times the free fraction in the intracerebral nonspecifically bound compartment) was achieved using Logan analysis and kinetic analysis, with a total study time of 90 min. In the second experiment, (123)I-PE2I was administrated as a combined bolus and constant infusion. The bolus was equivalent to 2.7 h of constant infusion.


RESULTS
The bolus-to-infusion ratio of 2.7 h was based on the average terminal clearance rate from plasma in the bolus experiments. Steady state was attained in brain and plasma within 2 h, and time-activity curves remained constant for another 2 h. Even when an average bolus-to-infusion ratio was used, the striatal BP1 and BP2 values calculated with kinetic analysis (BP1 = 21.1 +/- 1.1; BP2 = 4.1 +/- 0.4) did not significantly differ from those calculated with bolus/infusion analysis (BP1 = 21.0 +/- 1.2; BP2 = 4.3 +/- 0.3). Computer simulations confirmed that a 2-fold difference in terminal clearance rate from plasma translates into only a 10% difference in BP1 and BP2 calculated from 120 to 180 min after tracer administration.


CONCLUSIONS
The bolus/infusion approach allows accurate and precise quantification of 123I-PE2I binding to dopamine transporter and is easily implemented in a clinical setting.
Neurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark. pinborg@nru.dk
Lars H
LH
Pinborg
Morten
M
Ziebell
Vibe G
VG
Frøkjaer
Robin
R
de Nijs
Claus
C
Svarer
Steven
S
Haugbøl
Stig
S
Yndgaard
Gitte M
GM
Knudsen
D000328:Adult; D000368:Aged; D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003198:Computer Simulation; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007261:Infusions, Intra-Arterial; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009662:Nortropanes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; D019275:Radiopharmaceuticals