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  • 1
    ISSN: 1619-7089
    Keywords: Key words: Small animal positron emission tomography ; Tracer Kinetics ; CFT ; Raclopride ; WAY-100635
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. With the stated aim of scanning small regions of interest in mice, several high-resolution positron emission tomographic (PET) systems are presently under development. Some, however, have low sensitivity and require high doses of radioactivity to achieve count statistics adequate to reconstruct small volumes. Using in vivo dissociation constants for three carbon-11 labelled ligands previously measured in rat brain, the present paper utilises simple saturation kinetics to estimate the limits on radioactivity and specific activity, to minimise the degree of receptor occupancy and achieve maximal specific binding of the radioligand. The extent of the problem is exemplified by considering a high-affinity ligand (dissociation constant in vitro ∼0.1 nM; in vivo ∼5 nmol/kg i.v. injected dose), where routinely produced levels of specific activity (∼100 MBq/nmol) would limit the activity injected into mice to ∼0.1 MBq for a 1% receptor occupancy. If, as is feasible, the new generation of high resolution PET systems requires an injected activity 〉10 MBq, then a 〉100-fold increase in specific activity would be needed for tracer kinetics to hold. The paper highlights the need to consider realistically achievable goals if high-resolution PET is to be accepted as a viable methodology to acquire pharmacologically and physiologically accurate ligand-receptor binding data in mice.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1619-7089
    Keywords: Key words: Positron emission tomography –α2-adrenoceptor – RS-15385-197 – RS-79948-197
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Carbon-11 labelled RS-15385-197 and its ethylsulphonyl analogue, RS-79948-197, were evaluated in rats as potential radioligands to image central α2-adrenoceptors in vivo. The biodistributions of both compounds were comparable with that obtained in an earlier study using tritiated RS-79948-197 and were consistent with the known localisation of α2-adrenoceptors. The maximal signals (total to non-specific binding) were, however, reduced, in the order [11C]RS-79948-197 〈 [11C]RS-15385-197 〈 [3H]RS-79948-197, primarily due to the difference in radiolabel position (O-methyl for carbon-11 compared with S-ethyl for tritium). This resulted in the in-growth of radiolabelled metabolites in plasma, which, in turn, contributed to the non-specific component of brain radioactivity. Nonetheless, the signal ratio of ∼5 for a receptor-dense tissue compared with the receptor-sparse cerebellum, at 90–120 min after radioligand injection, encouraged the development of [O-methyl-11C]RS-15385-197 for human positron emission tomography (PET). Unfortunately, in two human PET scans (each of 90 min), brain extraction of the radioligand was minimal, with volumes of distribution more than an order of magnitude lower than that measured in rats. Following intravenous injection, radioactivity was retained in plasma and metabolism of the radiolabelled compound was very low. Retrospective measurements of in vitro plasma protein binding and in vivo brain uptake index (BUI) in rats demonstrated a higher protein binding of the radioligand in human compared with rat plasma and a lower BUI in the presence of human plasma. It is feasible that a higher affinity of RS-15385-197 for human plasma protein compared with receptor limited the transport of the radioligand. Although one of the PET scans showed a slight heterogeneity in biodistribution of radioactivity which was consistent with the known localisation of α2-adrenoceptors in human brain, it was concluded that [O-methyl-11C]RS-15385-197 showed little promise for routine quantification of α2-adrenoceptors in man.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1619-7089
    Keywords: Left ventricular volumes ; Left ventricular function ; Positron emission tomography ; Gating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To date cardiac positron emission tomography (PET) studies have focussed on the measurement of myocardial blood flow, metabolism and receptors while left ventricular (LV) function and dimensions have been derived from other modalities. The main drawback of this approach is the difficulty of data co-registration, which limits clinical interpretation. The aim of this study was to evaluate whether it is possible to measure absolute cardiac volumes, and consequently LV function parameters such as ejection fraction, and wall motion with gated PET. Nineteen patients underwent a PET scan and planar radionuclide ventriculography (MUGA) within 9±9 days. A 9-min scan (16 gates/cardiac cycle) was acquired after inhalation of 3 MBq/ml of oxygen-15 labelled carbon monoxide at the rate of 500 m1/min over 4 min using a multislice PET camera. Noise reduction was performed on the gated image to enhance the definition of the ventricles before reslicing to the short-axis view. A threshold value was used to detect the edge of the LV at each gate. LV volumes at each gate were estimated by summing the volume of voxels within the LV boundary. PET measurements of LV volumes were as follows: LV end-diastolic volume ranged from 72 to 233 ml and LV end-systolic volume ranged from 24 to 203 ml. Phantom experiments supported the validity of this approach for estimating volumes. LV ejection fraction measured with MUGA was 38.4%±16.3% (range 15%–71%) and that measured with PET was 39.6%±17.7% (range 9%–72%) (P=NS). The LV ejection fraction measurements were highly correlated (r 2=0.824). These results indicate that: (1) absolute enddiastolic and end-systolic volumes can be quantified using gated PET and (2) LV ejection fraction can be accurately measured by gated PET simultaneously with the other physiological PET parameters.
    Type of Medium: Electronic Resource
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