The Measurement of Sensitivity and Comparative Analysis of Simplified Quantitation Methods to Measure Dopamine Transporters Using [ I-123 ] IPT Pharmacokinetic Computer Simulations

Son, Hye Kyung; Kim, Hee Joung; Nha, Sang Kyun; Lee, Hee Kyung

Abstract

Recently, [I-123]IPT SPECT has been used for early diagnosis of Parkinson's patients(PP) by imaging dopamine transporters. The dynamic time activity curves in basal ganglia(BG) and occipital cortex(OCC) without blood samples were obtained for 2 hours. These data were then used to measure dopamine transporters by operationally defined ratio methods of (BG-OCC)/OCC at 2 hrs, binding potential Rv=k3/k4 using graphic method or RA= (ABBG-ABOCC)/ABOCC for 2 hrs, where ABBG represents accumulated binding activity in basal ganglia(integral 0 120minBG(t)dt) and ABOCC represents accumulated binding activity in occipital cortex(integral 0 120minBG(t)dt). The purpose of this study was to examine the IPT pharmacokinetics and investigate the usefulness of simplified methods of (BG-OCC)/OCC, RA, and RA which are often assumed that these values reflect the true values of k3/k4. The rate constants K1, k2, k3 and k4 to be used for simulations were derived using [I-123]IPT SPECT and aterialized blood data with a standard three compartmental model. The sensitivities and time activity curves in BG and OCC were computed by changing K1 and k3(only BG) for every 5min over 2 hours. The values (BG-OCC)/OCC, RA, and Rv were then computed from the time activity curves and the linear regression analysis was used to measure the accuracies of these methods. The rate constants K1, k2, k3, k4 at BG and OCC were 1.26+/-5.41%, 0.044+/-19.58%, 0.031+/-24.36%, 0.008+/-22.78% and 1.36+/-4.76%, 0.170+/-6.89%, 0.007+/-23.89%, 0.007+/-45.09%, respectively. The Sensitivities for ((delta S/S)/(delta k3/k3)) and ((delta S/delta S)/(delta K1/K1)) at 30min and 120min were measured as (0.19, 0.50) and (0.61, 0.23), respectively. The correlation coefficients and slopes of ((BG-OCC)/OCC, RA, and Rv) with k3/k4 were (0.98, 1.00, 0.99) and (1.76, 0.47, 1.25), respectively. These simulation results indicate that a late [1-123]IPT SPECT image may represent the distribution of the dopamine transporters. Good correlations were shown between (BG-OCC)/OCC, RA or Rv and true k3/k4,, although the slopes between them were not unity. Pharmacokinetic computer simulations may be very useful technique in studying dopamine transpoter systems.