RAPID DETECTION OF PARKINSONS-DISEASE BY SPECT WITH ALTROPANE - A SELECTIVE LIGAND FOR DOPAMINE TRANSPORTERS

Increasing evidence indicates that dopamine (DA) transporter density d eclines in Parkinson's disease (PD). 2 beta-Carbomethoxy-3 beta-(4-flu orophenyl)-n-(1-iodoprop-1-en-3-yl) nortropane (IACFT, Altropane(TM)) is a cocaine analog with high affinity and selectivity for dopamine tr ansporter (DAT) sites in the striatum. In this study, single photon em ission computed tomography (SPECT) with [I-123]altropane was used to m easure DAT density in seven healthy volunteers (five males, age 37-75, and two females, ages 26 and 39) and eight male patients with Parkins on's disease (age 14-79, Hoehn and Yahr stage: 1.5-3 (n = 5) and 4-5 ( n = 3)). Dynamic SPECT images and arterial blood samples were acquired over 1.5-2 hr and plasma radioactivity was analyzed chromatographical ly to obtain metabolite corrected arterial input functions. Binding po tential (BP, B'(max)/K-D) for striatal (Str) DAT sites was calculated by two methods using occipital cortex (Occ) as a reference. In the fir st method, tissue time-activity curves (TAC) and metabolite corrected arterial input functions were analyzed by a linear graphical method de veloped for reversible receptor ligands. In the second method, the exp ression(Str(TAC) - Occ(TAC)) was fitted to a gamma variate function an d the maximum divided by Occ(TAC) at the same time was used to estimat e BP. In five of the PD patients, the SPECT data were compared with th e results of PET with [F-18] B-fluoro DOPA (FD-PET). Plasma analysis i ndicated that [I-123]altropane is rapidly converted to polar metabolit es. SPECT images in healthy volunteers showed that [I-123] altropane a ccumulated rapidly and selectively in the striatum and yielded excelle nt quality images within 1 h after injection. Both methods of analysis revealed a 7.6%/decade reduction in BP and average striatal values (c orrected to age 25) were 1.83 +/- 0.22 and 2.09 +/- 0.20 by methods 1 and 2. In all the PD patients, striatal accumulation was markedly redu ced and the pattern of loss was similar to that reported for DA; most profound in the posterior putamen with relative sparing of the caudate nuclei. A comparable pattern was observed with ED-PET For total stria tum, age-corrected BP was significantly (P < 0.001) reduced; 0.83 +/- 0.06 (method 1), 0.84 +/- 0.07 (method 2). BPs measured by the two met hods were remarkably similar and highly correlated r(2) = 0.88,(P < 0. 001). These results indicate that [I-123]altropane is an excellent SPE CT ligand for imaging the DAT/DA neurons in human brain. The high sele ctivity and rapid striatal accumulation of the ligand allows for accur ate quantitation of DAT sites in less than 2 hr. The results further d emonstrate that [I-123]altropane is an effective marker for PD. (C) 19 98 Wiley-Liss, Inc.