We describe the introduction of positron emission tomography/computed tomography (PET/CT) to the ... more We describe the introduction of positron emission tomography/computed tomography (PET/CT) to the investigation of patients with cancer. The first such unit in the UK and its mode of operation is discussed and initial applications shown. Five hundred and thirty-five patients have been scanned with 2-[18F]fluoro-2-deoxy-D-glucose from mid-January 2002 to the end of August 2002. From this initial experience a clear view of the impact of this technology is emerging. It can now be stated that (1) PET/CT does speed up the throughput of patient studies by at least 25% and hence adds to the comfort of patients scanned; and (2) PET/CT leads to greater accuracy in the interpretation of data. In view of the routine availability of high quality PET and CT fused maps a significant development in radiotherapy planning is on the horizon. We discuss our experience at present and point to further developments in the near future.
To investigate the effect of co-administered polyethylene glycol 400 (PEG 400), a pharmaceutical ... more To investigate the effect of co-administered polyethylene glycol 400 (PEG 400), a pharmaceutical excipient previously shown to accelerate small intestinal transit, on the absorption characteristics of ranitidine from the gastrointestinal tract. Ten healthy male volunteers each received, on two separate occasions, an immediate-release pellet formulation of ranitidine (150 mg) encapsulated within a hard gelatin capsule and a liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange juice containing 10 g PEG 400 (test). The liquid preparations were also radiolabelled with indium-III to allow their transit through the gastrointestinal tract to be followed using a gamma camera. On a further occasion an intravenous injection of ranitidine (50 mg) was administered. Blood samples were taken over a 12 h period on each study day to allow a ranitidine plasma and subsequent absorption rate profile to be generated for each oral formulation. Urine was collected for 24 h and ...
The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimate... more The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimated striatal D2 dopamine binding in schizophrenic patients treated with sertindole using 123I iodobenzamide (IBZM) SPET. Patients were recruited from a clinical trial of sertindole's tolerability and efficacy. Striatal D2 binding in sertindole-treated patients (n = 5), was compared with previously reported data from clozapine (n = 10); olanzapine (n = 6); typical antipsychotic responsive (n = 10); and risperidone (n = 6)-treated groups. Mean PANSS (structured clinical interview for the positive and negative syndrome scale) scores showed clinical improvement in the sertindole group. Few extrapyramidal side effects (EPS) were recorded [average Simpson-Angus (SAS) score = 2.6]. Sertindole-treated patients had mean D2 binding indices (+/-SE) significantly lower than clozapine-treated patients (1.19 +/- 0.04) versus (1.49 +/- 0.04), and olanzapine-treated patients (1.41 +/- 0.06); and similar to those of risperidone (1.24 +/- 0.04) and typical antipsychotic responsive (1.25 +/- 0.05) treated patients. In this patient sample the preliminary evidence suggests that sertindole's decreased tendency to induce EPS at clinically therapeutic doses is not due to limited occupancy of striatal D2 receptors in vivo, and as is the case for risperidone, patients are protected from EPS by some other intrinsic effect of the drug.
. Background: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor... more . Background: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms. Method: 5-HT2A binding was estimated using 123I-5-I-R91150 and single photon emission tomography (SPET) in six schizophrenic subjects treated with quetiapine at a mean (±SD) daily dose of 350±123 mg for at least 5 weeks and a matched sample of six healthy volunteers. Clinical and side-effect ratings were performed at baseline and at the time of SPET scanning. The reference region approach was used to define a 5-HT2A binding index in the frontal and temporal cortex. Results: Quetiapine treatment resulted in a significant decline in 5-HT2A receptor availability in the frontal cortex (mean 0.98±0.09) relative to healthy volunteers (mean 1.33±0.16). All patients showed improvements in clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio after quetiapine treatment was significantly negatively correlated with reduction in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05 Bonferroni corrected), but not with the reduction in the scores from the scale for the assessment of positive symptoms, the scale for the assessment of negative symptoms, the Montgomery-Asberg depression rating scale or patient age. Conclusion: Quetiapine treatment results in significant in vivo blockade of cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.
Regional cerebral blood flow (rCBF) was investigated in a group of medicated DSM-III-R schizophre... more Regional cerebral blood flow (rCBF) was investigated in a group of medicated DSM-III-R schizophrenic patients and age, sex and handedness matched normal volunteers using a split-dose 99mTc-HMPAO Single Photon Emission Tomography (SPET) protocol. Measures were taken during the performance of a verbal memory task aimed at activating the left medial temporal lobe, a region repeatedly suggested to be structurally abnormal in schizophrenia. In normal subjects, the performance of the task was associated with significant rCBF increases in the left medial temporal, left inferior frontal and anterior cingulate cortices, and right cerebellum. Despite their significantly poorer performance on the memory task, the degree of medial temporal activation measured in the schizophrenic patients was not significantly different from that found in the control group. This finding suggests that memory deficits in schizophrenia do not necessarily imply failure to activate the left medial temporal lobe as assessed by 99mTc-HMPAO SPET.
[(123)I]CNS-1261 [N-(1-naphthyl)-N&am... more [(123)I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intra-channel PCP/ketamine/MK-801 site of the N-methyl-d-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intra-channel PCP/ketamine/MK-801 site) on [(123)I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [(123)I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [(123)I]CNS-1261 V(T) in most of the brain regions examined (P<.05). [(123)I]CNS-1261 appears to be a specific ligand in vivo for the intra-channel PCP/ketamine/MK-801 NMDA binding site.
Pharmacologic coronary vasodilation with adenosine, combined with myocardial scintigraphy, is a u... more Pharmacologic coronary vasodilation with adenosine, combined with myocardial scintigraphy, is a useful test for the diagnosis of coronary artery disease (CAD) in patients unable to exercise. It has been demonstrated recently that exercise 99mTc-labeled tetrofosmin cardiac imaging can be used for the detection of CAD. However, no data are available comparing 99mTc-labeled tetrofosmin adenosine and exercise tests in the same patients. The results of adenosine and exercise 99mTc-labeled tetrofosmin myocardial tomography were compared in 41 patients (37 men and four women; mean age 53 +/- 8 years) with suspected or known CAD who underwent coronary angiography. All patients were submitted, on separate days, to three injections of 99mTc-labeled tetrofosmin (740 MBq intravenously): one at rest, one during bicycle exercise, and one during adenosine infusion (140 micrograms/kg/min for 6 minutes with injection of 99mTc-labeled tetrofosmin at 4 minutes). A total of 902 myocardial segments were analyzed quantitatively. One patient had normal coronary vessels, 19 patients had single-vessel CAD, 12 patients had two-vessel CAD, and nine patients had three-vessel CAD (> 50% coronary stenosis) on coronary angiography. Adenosine induced a significant increase in heart rate (88 +/- 16 beats/min at peak vs 72 +/- 11 beats/min at rest; p < 0.01). Systolic and diastolic blood pressure was not significantly different after adenosine infusion compared with rest. Double product was 22931 +/- 7039 at peak exercise and 11229 +/- 3413 after adenosine (p < 0.01). Agreement on the presence of abnormal single-photon emission computed tomography by adenosine and exercise was 100% by quantitative analysis. In all segments a significant relationship between exercise and adenosine 99mTc-99m-labeled tetrofosmin uptake was observed (r = 0.90; p < 0.001). Segmental agreement for regional 99mTc-labeled tetrofosmin uptake score between exercise and adenosine was observed in 737 (82%) of the 902 segments (kappa value of 0.66). Concordance between the two studies for identification of perfusion status was observed in 809 (90%) of the segments (kappa value of 0.80). Sensitivity and specificity for detection of stenosed vessels were not different for dynamic exercise stress testing and adenosine 99mTc-labeled tetrofosmin cardiac tomography. Despite different hemodynamic effects, adenosine and dynamic exercise 99mTc-labeled tetrofosmin single-photon emission computed tomographic imaging provides similar information in the diagnosis and localization of CAD.
We describe the introduction of positron emission tomography/computed tomography (PET/CT) to the ... more We describe the introduction of positron emission tomography/computed tomography (PET/CT) to the investigation of patients with cancer. The first such unit in the UK and its mode of operation is discussed and initial applications shown. Five hundred and thirty-five patients have been scanned with 2-[18F]fluoro-2-deoxy-D-glucose from mid-January 2002 to the end of August 2002. From this initial experience a clear view of the impact of this technology is emerging. It can now be stated that (1) PET/CT does speed up the throughput of patient studies by at least 25% and hence adds to the comfort of patients scanned; and (2) PET/CT leads to greater accuracy in the interpretation of data. In view of the routine availability of high quality PET and CT fused maps a significant development in radiotherapy planning is on the horizon. We discuss our experience at present and point to further developments in the near future.
To investigate the effect of co-administered polyethylene glycol 400 (PEG 400), a pharmaceutical ... more To investigate the effect of co-administered polyethylene glycol 400 (PEG 400), a pharmaceutical excipient previously shown to accelerate small intestinal transit, on the absorption characteristics of ranitidine from the gastrointestinal tract. Ten healthy male volunteers each received, on two separate occasions, an immediate-release pellet formulation of ranitidine (150 mg) encapsulated within a hard gelatin capsule and a liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange juice containing 10 g PEG 400 (test). The liquid preparations were also radiolabelled with indium-III to allow their transit through the gastrointestinal tract to be followed using a gamma camera. On a further occasion an intravenous injection of ranitidine (50 mg) was administered. Blood samples were taken over a 12 h period on each study day to allow a ranitidine plasma and subsequent absorption rate profile to be generated for each oral formulation. Urine was collected for 24 h and ...
The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimate... more The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimated striatal D2 dopamine binding in schizophrenic patients treated with sertindole using 123I iodobenzamide (IBZM) SPET. Patients were recruited from a clinical trial of sertindole's tolerability and efficacy. Striatal D2 binding in sertindole-treated patients (n = 5), was compared with previously reported data from clozapine (n = 10); olanzapine (n = 6); typical antipsychotic responsive (n = 10); and risperidone (n = 6)-treated groups. Mean PANSS (structured clinical interview for the positive and negative syndrome scale) scores showed clinical improvement in the sertindole group. Few extrapyramidal side effects (EPS) were recorded [average Simpson-Angus (SAS) score = 2.6]. Sertindole-treated patients had mean D2 binding indices (+/-SE) significantly lower than clozapine-treated patients (1.19 +/- 0.04) versus (1.49 +/- 0.04), and olanzapine-treated patients (1.41 +/- 0.06); and similar to those of risperidone (1.24 +/- 0.04) and typical antipsychotic responsive (1.25 +/- 0.05) treated patients. In this patient sample the preliminary evidence suggests that sertindole's decreased tendency to induce EPS at clinically therapeutic doses is not due to limited occupancy of striatal D2 receptors in vivo, and as is the case for risperidone, patients are protected from EPS by some other intrinsic effect of the drug.
. Background: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor... more . Background: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms. Method: 5-HT2A binding was estimated using 123I-5-I-R91150 and single photon emission tomography (SPET) in six schizophrenic subjects treated with quetiapine at a mean (±SD) daily dose of 350±123 mg for at least 5 weeks and a matched sample of six healthy volunteers. Clinical and side-effect ratings were performed at baseline and at the time of SPET scanning. The reference region approach was used to define a 5-HT2A binding index in the frontal and temporal cortex. Results: Quetiapine treatment resulted in a significant decline in 5-HT2A receptor availability in the frontal cortex (mean 0.98±0.09) relative to healthy volunteers (mean 1.33±0.16). All patients showed improvements in clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio after quetiapine treatment was significantly negatively correlated with reduction in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05 Bonferroni corrected), but not with the reduction in the scores from the scale for the assessment of positive symptoms, the scale for the assessment of negative symptoms, the Montgomery-Asberg depression rating scale or patient age. Conclusion: Quetiapine treatment results in significant in vivo blockade of cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.
Regional cerebral blood flow (rCBF) was investigated in a group of medicated DSM-III-R schizophre... more Regional cerebral blood flow (rCBF) was investigated in a group of medicated DSM-III-R schizophrenic patients and age, sex and handedness matched normal volunteers using a split-dose 99mTc-HMPAO Single Photon Emission Tomography (SPET) protocol. Measures were taken during the performance of a verbal memory task aimed at activating the left medial temporal lobe, a region repeatedly suggested to be structurally abnormal in schizophrenia. In normal subjects, the performance of the task was associated with significant rCBF increases in the left medial temporal, left inferior frontal and anterior cingulate cortices, and right cerebellum. Despite their significantly poorer performance on the memory task, the degree of medial temporal activation measured in the schizophrenic patients was not significantly different from that found in the control group. This finding suggests that memory deficits in schizophrenia do not necessarily imply failure to activate the left medial temporal lobe as assessed by 99mTc-HMPAO SPET.
[(123)I]CNS-1261 [N-(1-naphthyl)-N&am... more [(123)I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intra-channel PCP/ketamine/MK-801 site of the N-methyl-d-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intra-channel PCP/ketamine/MK-801 site) on [(123)I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [(123)I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [(123)I]CNS-1261 V(T) in most of the brain regions examined (P<.05). [(123)I]CNS-1261 appears to be a specific ligand in vivo for the intra-channel PCP/ketamine/MK-801 NMDA binding site.
Pharmacologic coronary vasodilation with adenosine, combined with myocardial scintigraphy, is a u... more Pharmacologic coronary vasodilation with adenosine, combined with myocardial scintigraphy, is a useful test for the diagnosis of coronary artery disease (CAD) in patients unable to exercise. It has been demonstrated recently that exercise 99mTc-labeled tetrofosmin cardiac imaging can be used for the detection of CAD. However, no data are available comparing 99mTc-labeled tetrofosmin adenosine and exercise tests in the same patients. The results of adenosine and exercise 99mTc-labeled tetrofosmin myocardial tomography were compared in 41 patients (37 men and four women; mean age 53 +/- 8 years) with suspected or known CAD who underwent coronary angiography. All patients were submitted, on separate days, to three injections of 99mTc-labeled tetrofosmin (740 MBq intravenously): one at rest, one during bicycle exercise, and one during adenosine infusion (140 micrograms/kg/min for 6 minutes with injection of 99mTc-labeled tetrofosmin at 4 minutes). A total of 902 myocardial segments were analyzed quantitatively. One patient had normal coronary vessels, 19 patients had single-vessel CAD, 12 patients had two-vessel CAD, and nine patients had three-vessel CAD (> 50% coronary stenosis) on coronary angiography. Adenosine induced a significant increase in heart rate (88 +/- 16 beats/min at peak vs 72 +/- 11 beats/min at rest; p < 0.01). Systolic and diastolic blood pressure was not significantly different after adenosine infusion compared with rest. Double product was 22931 +/- 7039 at peak exercise and 11229 +/- 3413 after adenosine (p < 0.01). Agreement on the presence of abnormal single-photon emission computed tomography by adenosine and exercise was 100% by quantitative analysis. In all segments a significant relationship between exercise and adenosine 99mTc-99m-labeled tetrofosmin uptake was observed (r = 0.90; p < 0.001). Segmental agreement for regional 99mTc-labeled tetrofosmin uptake score between exercise and adenosine was observed in 737 (82%) of the 902 segments (kappa value of 0.66). Concordance between the two studies for identification of perfusion status was observed in 809 (90%) of the segments (kappa value of 0.80). Sensitivity and specificity for detection of stenosed vessels were not different for dynamic exercise stress testing and adenosine 99mTc-labeled tetrofosmin cardiac tomography. Despite different hemodynamic effects, adenosine and dynamic exercise 99mTc-labeled tetrofosmin single-photon emission computed tomographic imaging provides similar information in the diagnosis and localization of CAD.
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