European Journal of Nuclear Medicine and Molecular Imaging Vol. 30, No. 7, July 2003 Abstract. Technetium-99m hexamethylpropylene amine oxime (HMPAO) and 99m Tc-N,N”-1,2-ethylene diylbis-L- cysteine diethyl ester dihydrochloride (ECD) yield sig- nificantly different images of cerebral perfusion owing to their particular pharmacokinetics. The aim of this study was to assess the topography, extension and statis- tical significance of these differences in Alzheimer’s dis- ease (AD). Sixty-four patients with mild to moderate AD were retrospectively selected by two European centres. Two series of patients, including 32 studied with 99m Tc- HMPAO single-photon emission tomography (SPET) and 32 studied with 99m Tc-ECD SPET, were matched for sex, age (±3 years) and severity of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE) (±2 points), following a case-control proce- dure. SPET data were processed using SPM99 software (uncorrected height threshold: P=0.001). 99m Tc-ECD SPET gave significantly higher uptake ratio values than 99m Tc-HMPAO SPET in several symmetrical clusters, in- cluding the right and left occipital cuneus, the left occip- ital and parietal precuneus, and the left superior and mid- dle temporal gyri. 99m Tc-HMPAO SPET gave signifi- cantly higher uptake ratio values than ECD in two small- er clusters, including the hippocampus in both hemi- spheres. In AD, relative brain uptake of 99m Tc-HMPAO and 99m Tc-ECD is different in several brain regions, some of which are typically involved in AD, such as the precuneus and the hippocampus. These differences con- firm the need for specific normal databases, but their im- pact on routine SPET reports in AD is not known and deserves an ad hoc investigation. Keywords: 99m Tc-HMPAO – 99m Tc-ECD – Alzheimer’s disease – Statistical parametric mapping Eur J Nucl Med Mol Imaging (2003) 30:1009–1013 DOI 10.1007/s00259-003-1193-2 Introduction Both technetium-99m hexamethylpropylene amine oxime (HMPAO) and 99m Tc-N,N”-1,2-ethylene diylbis-L- cysteine diethyl ester dihydrochloride (ECD) are widely employed to perform brain single-photon emission to- mography (SPET) in nuclear medicine centres. Although a moderately better internal (i.e. grey-to-white matter ratio) and external (i.e. brain-to-body ratio) contrast is achieved with ECD [1], the choice usually depends ei- ther on the specific radiochemical properties that lead to different timing in dose preparation and in waiting be- fore scanning, or on the greater confidence of the nuclear medicine specialist with images of one of the two. How- ever, evidence is growing that the two radiopharmaceuti- cals perform differently both in normal subjects [1, 2] and in several pathological conditions, such as subacute non-cortical stroke and herpes simplex encephalitis [3]. Uptake differences have been found in several cortical regions, including the mesial temporal lobe and the tem- poroparietal cortex [1, 2, 3]. Alzheimer’s disease (AD) is one of the pathological conditions most investigated by SPET and is characterised by reduced tracer uptake in the posterior cingulate, precuneus, posterior temporopa- rietal associative cortex [4] and the mesial temporal lobe [4, 5], i.e. in areas that may exhibit different distribution of the compounds. In practice, the degree of pathologically induced mod- ifications is commonly thought to exceed the variations in radiopharmaceutical distribution, and this would ex- plain why the two tracers show a comparable perfor- mance in AD. However, it is not known whether the Pierre Malick Koulibaly ( ✉ ) Laboratoire de Biophysique, Université de Nice-Sophia Antipolis, UFR de Médecine, 28 Avenue de Valombrose, 06107 Nice Cedex 2, France e-mail: koulibal@unice.fr Tel.: +33-49-3377713, Fax: +33-49-3377717 Short communication 99m Tc-HMPAO and 99m Tc-ECD perform differently in typically hypoperfused areas in Alzheimer’s disease Pierre Malick Koulibaly 1 , Flavio Nobili 2 , Octave Migneco 1 , Paolo Vitali 2 , Philippe H. Robert 3 , Nicola Girtler 2 , Jacques Darcourt 1 , Guido Rodriguez 2 1 Nuclear Medicine Department, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, France 2 Clinical Neurophysiology, Department of Internal Medicine, University of Genoa, Italy 3 Memory Center, Federation of Clinical Neuroscience, Centre Hospitalier Universitaire, University of Nice-Sophia Antipolis, France Received: 6 December 2002 / Accepted: 15 March 2003 / Published online: 15 May 2003 © Springer-Verlag 2003