Browsing by Author "Kassiou, M"

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    Attenuation correction for the large non-human primate brain imaging using microPET
    (IOP Publishing Ltd, 2010-04-21) Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, RB; Meikle, SR
    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a (57)Co transmission point source with a 4% energy window. The optimal energy window for a (68)Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for (57)Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [(18)F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass (57)Co (4% energy window) or (68)Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner. © 2010, IOP Publishing LTD.
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    Decreased vesicular acetylcholine transporter and α4β2 nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning
    (Elsevier, 2007-03-26) Quinlivan, M; Chalon, S; Vergote, J; Henderson, J; Katsifis, A; Kassiou, M; Guilloteau, D
    Degeneration of cholinergic neurons is a well known characteristic of Alzheimer's disease (AD). Two radioligands were studied in a rat model of cholinergic degeneration to evaluate their potential efficacy for molecular imaging of AD. Following specific cholinergic-cell immunolesioning with 192 IgG-saporin (SAP), ex vivo autoradiography was performed with 123IBVM, a radioligand which targets the vesicular acetylcholine transporter (VAChT). Following the decay of 123I, the same animals had in vitro autoradiography performed with 125I-A-85380, a marker for nicotinic acetylcholine receptors (nAChRs). As expected significant, widespread decreases in 123IBVM uptake were observed in SAP treated animals. Moderate but significant reductions in 125I-A-85380 binding in the hippocampus (Hip) and cerebellum (Cbm) were also observed following SAP immunolesioning. The results with 123IBVM confirm and extend previous work investigating the uptake of radioiodinated IBVM in this animal model. The results with 125I-A-85380 are unique and are in contrast with work performed in this animal model with other nAChR radioligands, indicating the favourable properties of this radioligand for molecular imaging. © 2006 Elsevier Ireland Ltd.
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    France Australia collaboration in nuclear medicine and biology: 10 years of success
    (Australian Nuclear Science and Technology Organisation, 2002-04-29) Loc'h, C; Katsifis, A; Kassiou, M
    In 1992, a collaboration in Nuclear Biomedicine was initiated with the support of the French Embassy in Australia. From a meeting held in Sydney that year, the following 3 objectives were decided: 1. Development of new radiopharmaceuticals. This subject involved the design, synthesis and radiolabelling with positron emitters (carbon-11, fluorine-18, bromine-76) for positron tomography (PET) and with iodine-123 for single photon tomography (SPET) of novel ligands and their radiopharmacological evaluation. 2. Improvement of instrumentation and data processing: measurement of input function, data analysis of medical images, motion detection/correction. 3. Development of clinical investigations in the fields of diagnosis and metabolic radiotherapy of melanoma, assessment of myocardial viability, studies of neurodegenerative and neuropsychiatric disorders. The form of the collaboration took advantage of the expertises and resources in each country. During 1992-2002 period, 11 centers from our 2 countries collaborated: a. from France: CEA-SHFJ (Orsay), INSERM U316 (Tours), CERMEP (Lyon) CEA-LETI (Grenoble), Centre J. PERRIN (Clermont-Ferrand), CHU (Nantes): CHU (Brest). b. from Australia: Radiopharmaceutical Division ANSTO, Menai, Centre for PET Austin Hospital, Melbourne, PET and Nuclear Medicine, RPAH, Sydney, Nuclear Medicine Westmead Hospital, Sydney, This scientific cooperation took the following forms: exchanges of information, visits of scientists, research and publication on joint projects and seminars. Specifically, the Orsay group collaborated with centers from Australia to develop and characterize new radiotracers and radiopharmaceuticals for research or clinical use and to establish protocols to investigate physiological and pathological mechanisms in humans or animals, especially in the area of neurotransmission (neurodegenerative diseases, psychiatric disorders). As main results of these collaborations, 3 main subjects were achieved and followed by articles published in well recognized scientific journals.
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    Progress in radiopharmaceutical development in the Australasia region
    (The Institution of Engineers Australia, 1994-05-01) Lambrecht, RM; Katsifis, A; Kassiou, M; Smith, SV
    Recent progress in the development of reactor and cyclotron produced radionuclides, conversion to precursors, synthesis, quality control and biomedical applications are highlighted with examples of prospective radiopharmaceuticals applicable to major diseases of the Australasia region. The merits of cyclotrons and nuclear reactors for medical radioisotopes in the region are cited
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    Trishomocubanes: novel σ ligands modulate cocaine-induced behavioural effects
    (Elsevier Science B.V., 2007-01-19) Liu, X; Banister, SD; Christie, MJ; Banati, RB; Meikle, SR; Coster, MJ; Kassiou, M
    Trishomocubane analogues TC1 (N-(3′-fluorophenyl)ethyl-4-azahexacyclo [5.4.1.02,6.03,10.05,9.08,11]dodecan-3-ol) and TC4 (N-(3′-fluorophenyl)methyl-4-azahexacyclo [5.4.1.02,6.03,10.05,9.08,11]dodecan-3-ol) were evaluated for their modulatory effects on locomotor activity as well as interactions with cocaine-induced responses. TC1 and TC4 have high affinity and moderate to high selectivity for σ1 (Ki = 10 nM, σ1/σ2 = 0.03) and σ2 (Ki = 20 nM, σ1/σ2 = 7.6) receptor subtypes respectively. Both compounds have negligible affinity for the dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters. In behavioural studies, TC1 produced a dose-related inhibition in spontaneous locomotor activity measured in a Digiscan apparatus. TC1 attenuated the stimulatory locomotor effect of 20 mg/kg cocaine with a half-maximal depressant activity (ID50) of 38.6 mg/kg. TC1 (dose range of 25 to 100 mg/kg) also partially substituted for the effect of cocaine (10 mg/kg) in a discriminative stimulus task, involving the trained discrimination between cocaine and saline using a two-lever choice method. Following a dose of 50 mg/kg TC1, a maximum of 31% substitution was reached. The response rate was reduced to 56% of vehicle control following a TC1 dose of 100 mg/kg. These behavioural effects suggest that TC1 can act as an antagonist via the σ1 receptor. In contrast to TC1, TC4 produced a stimulant effect in locomotor activity with the ED50 estimated at 0.94 mg/kg. In addition, TC4 failed to inhibit cocaine-induced stimulation; neither did it substitute for the discriminative stimulus effects of cocaine. TC4 thus appears to interact predominantly with the σ2 receptor subtype (σ1/σ2 = 7.6) which may result in dopamine stimulation independent of the effects of cocaine. The differential effect of TC1 and TC4 warrants further study of the mechanism of these actions. Present data also suggests a potential role for trishomocubane analogues in developing medication or research tools for cocaine addiction. © 2007, Elsevier Ltd.