EurPsychiatry 1998;13 (Suppl 1):9s-14s © Elsevier, Paris IBZM-SPECT imaging of dopamine D2 receptors with typical and atypical antipsychotics S Kasper 1, J Tauscher ~, E Ktifferle ~, B Hesselmann ~, C Barnas ~, T Brticke 2 1 Department of General Ps3chiatry. University of Vienna, Wahringer Gurte118-20, A-1090; ~ Department of G~'neral Neurology, University of Vienna. Vienna, Austria SUMMARY - Considerable progress has been achie'red over the past 15 years in uncovering the biological basis of major psychiatricdisorders. Since psychopharmacological treatment is thought tc act on the underlying biological basis of the disease, brain imaging techniques enable us to understand the mechanism of action of such corlpounds. One important tool used to determine patterns of brain dysfunction and how psychopharmacologicalagents such as antipsychofi~: compounds work is single-photon emission computerised tomography (SPECT). This technique allows determination of striatai Dz receptor occupancy rates, which are associated with the extrapyramidal side effects (EPS) of antipsychoticdrugs. Studies have confirmed that atypical antipsychotic agents have lower occupancy rates than typical agents. No association has been found between D2 receptor occupancy rates n the striatum and antipsychotic efficacy, and it therefore appears that striatal l)z receptor oc~tlpancy rates are not necessary for the antipsychoti~ effect of such agents in schizophrenia.The availability of more refined radioligandswill help us not only to understand the action of antipsychoticsbut also the pathophysiology of schizophrenia. antipsychotics \ schizophrenia \ dopamine \ recept,~rs \ SPECT INTRODUCTION Several lines of research indicate that the symptoms of schizophrenia are due to hyperactivity oz' the dopa- minergic system. Furthermore, the efficacy of antipsy- chotic agents is thought to be related to their capacity to antagonise dopamine. In addition to schizophrenia, dopaminergic neurons also play an impor:ant rote in Huntington's chorea, Parkinson's disease a ad, to some extent, depression. Different types of dopamine receptors have recently been identified, and there is some evidence that, in ad- dition to the putative D~ and D2dopamine receptor sub- types, D3, D4, and D5 receptors may be iraportant in schizophrenia. As early as 1983, the technique of posi- tron emission tomography (PET) enabled ])2 receptor occupancy rates to be measured using [llC IN-methyl- spiperone as a tracer. In the past decade, the raclopride derivative [123I]benzamide ([lz3I]IBZM) has been de- veloped for the determination of D2 receptor occupancy rates via single-photon emission computerised tomo- graphy (SPECT) imaging (Brticke et al, 1991b). Kung et al (1990) confirmed that the maximum number of D2 binding sites identified is comparable to tl-at of spip- crone, demonstrating the comparability of PET and SPECT methodology. Several new antipsychotic agents have recently been introduced to the market or have been the subject of intensive research (Kasper, 1998; Lieberman, 1994). There was a great need for such research, as typical antipsychotics are burdened with a high side effect profile (in particular, extrapyramidal side effects [EPS]) and a lack of efficacy on negative symptoms (Kane, 1996). The clinical profile of an antipsychotic with a low or non-existent propensity for EPS and ef- ficacy on negative symptoms, in addition to antipsy- chotic properties, has been termed 'atypical'. Clozapine has been shown to fulfil this description, although it carries a risk of agranulocytosis. Risperidone was the next 'atypical antipsychotic' to reach the market, fol- lowed by sertindole and olanzapine. Quetiapine and ziprasidone are two other promising antipsychotics that are currently under investigation. IBZM TECHNIQUE AND EVALUATION [123I]IBZM is a raclopride derivative which has been developed specifically for SPECT imaging. It has been shown to bind reversibly, and with high affinity and