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Clinical Investigations |
1 Neurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark
2 Department of Anesthesia, University Hospital Rigshospitalet, Copenhagen, Denmark
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)-2ß-carboxymethoxy-3ß-(4'-methylphenyl)nortropane (PE2I) binding to brain dopamine transporter. Methods: Five healthy subjects (mean age, 50 y; range, 4068 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, 123I-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. Conclusion: The bolus/infusion approach allows accurate and precise quantification of 123I-PE2I binding to dopamine transporter and is easily implemented in a clinical setting.
Key Words: 123I-PE2I dopamine transporter SPECT kinetic analysis Logan analysis bolus/infusion analysis
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