Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease.
A loss of acetylcholine is one of the most consistent neurochemical findings in Alzheimer's disease (AD) post-mortem, but the debate concerning receptor abnormalities is unresolved. The aim of this investigation was to measure the density of acetylcholine muscarinic receptors in AD patients at various stages in the disease (N = 8) by synthesising a radio-iodinated version of quinuclidinyl benzilate QNB, a potent muscarinic antagonist. Deficits were identified by comparison with a control data set obtained from four elderly volunteers and then compared to the deficit in total functional activity in the same brain regions measured using the cerebral perfusion tracer technetium-99m hexamethylpropylene amine oxime. Iodine-123 (R,R)quinuclidinyl benzilate (QNB) was synthesised using a CuI assisted nucleophilic aromatic exchange reaction. 160 MBq of the radioligand (specific activity 400 Ci/mmol: dose 90 ng/kg) was administered to each subject. Diagnosis of AD was made using the CAMDEX and DSMIIIR criteria with a physical examination, full blood screen, CT and chest X-ray. All subjects were scanned at 21 h post injection on an SME810 emission tomograph. 123I(R,R)QNB activity in the controls was found to be consistent with the known distribution of muscarinic receptors with no activity in the cerebellum and low activity in the thalamus. In the AD patients deficits in 123I-QNB binding which exceeded the corresponding total functional regional perfusion deficit were not found in six of the patients and were observed only in the two most severely affected patients, both of whom were untestable on the cognitive battery.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Clinical Physics, Institute of Neurological Sciences, Glasgow, UK.
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DJ
Wyper
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Brown
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Patterson
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Owens
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Hunter
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Teasdale
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McCulloch
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008875:Middle Aged; D015609:Organotechnetium Compounds; D010091:Oximes; D011813:Quinuclidinyl Benzilate; D011877:Radionuclide Imaging; D011976:Receptors, Muscarinic / Q000032:analysis*; D019690:Technetium Tc 99m Exametazime
D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D010091:Oximes; D011976:Receptors, Muscarinic; D019690:Technetium Tc 99m Exametazime; D011813:Quinuclidinyl Benzilate