MEASUREMENT OF THE DOPAMINERGIC DEGENERATION IN PARKINSONS-DISEASE WITH [I-123] BETA-CIT AND SPECT - CORRELATION WITH CLINICAL FINDINGS ANDCOMPARISON WITH MULTIPLE SYSTEM ATROPHY AND PROGRESSIVE SUPRANUCLEAR PALSY

The cocaine derivative [I-123]beta-CIT binds with high affinity to dop amine uptake sites in the striatum and can be used to visualize dopami nergic nerve terminals in vivo in the human brain with SPECT. It has b een validated that the calculation of a simple ratio of specific/nondi splaceable binding during a period of binding-equilibrium in the stria tum about 20 hrs after bolus injection of the tracer gives a strong an d reliable index of the binding potential of dopamine uptake sites. Pr evious studies have shown that the dopaminergic deficit in patients wi th Parkinson's disease (PD) can clearly be visualized and quantified u sing this method. Our own results in a group of 113 patients with PD d emonstrate a 45% loss of striatal [I-123]beta-CIT binding in compariso n to age corrected control values. Highly significant correlations of SPECT findings with clinical data obtained from the UPDRS rating scale such as akinesia, rigidity, axial symptoms and activities of daily li ving are demonstrated, while no correlation is found with tremor. The signal loss in a region comprising the whole striatum ranges from 35% in Hoehn/Yahr stage I to over 72% in stage V and is highly significant ly correlated to the different stages of disease severity. A compariso n of [I-123]beta-CIT binding in the striatum contralaterally and ipsil aterally to the affected body side in 29 patients with hemiparkinson s hows a loss of striatal binding of 41% contralaterally and 30% ipsilat erally. Results from subregional analyses in caudate and putamen show relative sparing of the caudate nucleus in PD. Data in 9 patients with multiple system atrophy (MSA) and 4 patients with progressive supranu clear palsy (PSP) are similar to the findings in PD although the diffe rences between caudate and putamen are somewhat less marked. These dat a demonstrate that the dopaminergic nerve cell loss in PD and other di sorders with a dopaminergic lesion can be quantified with [I-123]beta- CIT and SPECT and that hopefully a preclinical or very early diagnosis is made possible. Such studies might also open the way for a better e valuation of neuroprotective strategies in PD. It does not seem to be possible however to differentiate PD and MSA or PSP with this method i n individual cases.