[New radiopharmaceuticals and imaging of the heart receptors].
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Biomedical subjects
Publications and source records attributed to F Fazio.
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The cerebral distribution of 99mTc-labeled d, l, hexamethyl-propylene-amine-oxime (99mTc-HMPAO) as a function of rCBF and time was examined in rats and in man. The results of this study confirm that 99mTc-HMPAO is distributed in brain in proportion to rCBF. However, the rapid systemic breakdown of the tracer in blood results in considerable difficulties in the assessment of the arterial concentration of the parent compound; incomplete extraction of 99mTc-HMPAO from blood to brain and significant efflux from brain represent further limitations in the use of this tracer for quantification of rCFB. Despite these limitations 99mTc-HMPAO is of potential interest for a qualitative assessment of rCBF in specific clinical conditions.
99mTc complexes of 2-ethyl-2-hydrobutyric acid, 2-hydroxyisobutyric acid and (+)- and (-)-citramalic acid are readily prepared in high yield and high purity by reduction of 99mTcO4- in the presence of excess ligand. The resulting agents are very stable in vitro, but can undergo some decomposition during chromatographic analysis unless appropriate precautions are taken. Biodistribution studies in rats and dogs show that these new 99mTc agents accumulate primarily in the kidney and urinary bladder.
We studied brain cortical radioactive tracer activity in a consecutive series of nine patients with acute hemispheric ischemic stroke at their first cerebral ischemic stroke at their first cerebral ischemic episode. Results from N,N,N'-trimethyl-N'- (2-hydroxy-3-methyl-5-[123-I]-iodobenzyl)-1,3 propanediamine-2HCl (four patients) and technetium Tc 99m hexamethylpropyleneamine oxime (five patients) single photon emission computed tomographic studies were compared with x-ray computed tomography (CT) and clinical findings within the first 48 hours, on day 10, and on day 30 after the clinical ictus. Cortical hypoactivity agreeing with the clinical findings was found on all initial scans but not in the follow-up studies. Cortical activity on the affected side in patients with stroke was significantly lower when compared with cortical activity in sex- and age-matched controls (n = 21). Computed tomography (with contrast) was less sensitive in detecting the ischemic lesions. These studies demonstrate that in the acute phase of stroke there is a single photon emission computed tomographic cortical disturbance that agrees with clinical findings, even when computed tomography scan infarction is limited to subcortical structures.
Positron emission tomography (PET) enables the study of neuropharmacological variables, such as regional receptor densities, alterations in receptor occupancy from endogenous neurotransmitters and exogenous drugs, and receptor plasticity in living human subjects. The purpose of this paper is to review the procedures currently used to study brain pharmacology based on the use of radioactive tracers and PET, and to identify open issues in this field. In particular, the article reviews methodology for tracer validation, including essential biochemistry and kinetic modeling, as well as present clinical applications of tracers used to study dopamine, opioid, benzodiazepine, and cholinergic receptors.
The correlation between clinical picture, CT scan and regional cerebral blood flow (rCBF) assessed by single photon emission computerized tomography (SPECT) was investigated in two patients with crossed aphasia. The presence and degree or right hemisphere dysfunction, beyond the areas affected by CT, closely paralleled the time course of language disturbances in both patients: transient aphasia in case 1 was associated with temporary reduction of perfusion in the right hemisphere, while in case 2 persistent aphasia and apraxia were found along with severe right hemisphere hypoperfusion three year after the onset of stroke.
The remote effects of small unilateral cerebrovascular lesions confined to subcortical structures were evaluated by single photon emission computerized tomography (SPECT) and a CBF tracer, I-123 HIPDM. A CBF study was performed in 34 patients presenting with subcortical stroke either in the acute or in the chronic stages. Twenty-one of the 34 patients showed areas of cortical hypoperfusion ipsilateral to the subcortical lesion. In 14 patients, asymmetry of perfusion was also observed at the cerebellar level, perfusion being significantly reduced in the cerebellar hemisphere contralateral to the lesion. There was no correlation between the degree and extension of these remote effects and the type of stroke (ischemic or hemorrhagic), the patency of cerebral arteries, or the size and site of the lesion by transmissive computerized tomography (TCT). Subcortical hematomas showed a correlation between occurrence of remote effects and time interval from the onset of stroke, occurring more frequently in the acute phase. A correlation was observed between cortical and cerebellar remote effects and the severity of clinical presentation. The causes of remote effects are still unclear and have been extensively debated. Our data indicate that there is a relationship of remote effect to the neurological status. It is possible to show, by noninvasive, low-cost methods, remote CBF effects after stroke that may contribute to the assessment of brain functional impairment.
The volume of extravascular lung water is currently measured in vivo from the difference in mean transit times of the extrapolated first-pass dilution curves of two indicators, one diffusible and the other confined to the intravascular space. To overcome the limitations of this method, one can prolong the measurement interval, introduce a highly diffusible indicator, or both. In the first case, recirculating indicators are measured and included in the computation by deconvolution of the mean transit time through the lung. In the second case, heat is used as the water indicator. In the third case, not yet explored, recirculating heat would be measured and long thermal transit times uncovered. In view of the complexity of the deconvolution method and the pitfalls of the thermal dilution method, a radiographic score of pulmonary edema may be more useful clinically to assess the volume of extravascular lung water in patients with heart disease or adult respiratory distress syndrome.
Cortical regional cerebral perfusion was assessed by N, N, N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1, 3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerised tomography (SPECT) in six aphasic and two neglect patients with unilateral subcortical vascular lesions. Assessments were carried out both in the acute phase and after a period ranging from 1 to 6 months after stroke onset. In all patients an almost complete spontaneous recovery occurred and was associated with a significant improvement of cortical perfusion. A relationship between severity of aphasia and degree of cortical hypoperfusion was found, in both the acute and the follow up assessments, in the aphasic subgroup.
Thirty-one patients with temporal lobe epilepsy (TLE) of mild to moderate severity, well controlled by pharmacotherapy (nonrefractory TLE), and with negative findings at computed tomography, were studied with magnetic resonance (MR) imaging at 1.5 T. Examination disclosed significant findings in 16 patients: mesial temporal abnormalities (n = 9), basitemporal abnormalities (n = 2), and alterations in frontoparietal white matter (n = 5). Coronal views and sequences with a 120-msec echo time (TE) depicted lesions in 16 patients; axial views depicted lesions in only nine of 16 patients; sequences with a 35-msec TE depicted lesions in only ten. These results underline the importance of screening with MR imaging in nonrefractory TLE patients and suggest that the MR imaging sequence of choice is a thin-section, coronal, T2-weighted sequence.
N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM), a synthetic basic compound with high affinity for lung tissue of various animal species, was labeled with 123I and injected into normal smokers (n = 9) and into asymptomatic smokers (n = 9). Time/activity curves were recorded for 90 min by gamma camera. HIPDM lung clearance was described by two exponential components. In smokers, the mean time of the first component, 10 +/- 1.4 min (mean +/- SEM), did not significantly differ from that of nonsmokers (9.7 +/- 0.9 min), whereas the mean time of the second component (12.9 +/- 0.6 h) was longer than that of nonsmokers (6.7 +/- 0.2 h). The intercept to the ordinate of the second exponential component was significantly higher in smokers (90.3 +/- 1.5%) than in nonsmokers (80.7 +/- 1.9%). Control studies in rabbits showed that, 2 min after intravenous injection, 95% of HIPDM is taken up by the lung; time/activity curves were similar to those obtained in humans. The longer pulmonary persistence of HIPDM in smokers may reflect an increased number of cellular binding sites or may be the expression of hindered HIPDM biotransformation. The rabbit can be used as a model to further investigate HIPDM kinetics in relation to lung dysfunction.
The detection of scattered radiation is recognized as one of the major sources of error in single photon emission computed tomography (SPECT). In this work three scatter correction techniques have been assessed and compared. Scatter coefficients and parameters characteristic of each technique have been calculated through Monte Carlo simulations and experimentally measured for various source geometries. Their dependence on the source/matter distribution and their spatial non-stationarity have been described. Each of the three scatter correction methods has then been tested on several SPECT phantom studies. The three methods provided comparable results. Following scatter compensation, both image quality and quantitative accuracy improved. In particular a slight improvement in spatial resolution and a statistically significant increase in cold lesion contrast, hot lesion recovery coefficient, and signal/noise ratio have been demonstrated with all methods.
Extravascular lung water (idQw1) is measured in vivo from the difference in mean transit times, computed by extrapolating the dilution curves, of two indicators, one freely diffusible, the other confined to the intravascular space. Using 3H2O it has been shown that idQw1 is smaller than the amount of extravascular water obtained from the difference between wet and dry lung weight (Qw1). Extrapolation allows one to use dilution curves for a short time, i.e., up to onset of obvious recirculation. Clearing the dilution curves or recirculation by deconvolution extends the observation time, which then becomes limited by sampling duration rather than onset of recirculation. This procedure entails recording recirculating tracers in the pulmonary artery (PA). Dilutions of tracers at input in PA and output in a systemic artery must be related to each other as continuous time functions. This is accomplished by means of a convolution integral. Deconvolution yields the frequency function of water molecule transit time in the extravascular lung space, l(t). In dogs and men, in both normal and edematous lungs, l(t) exhibits a knee and a fairly long tail. Extravascular lung water computed from l(t), idcQw1, agrees with Qw1 and correlates with data on the extravascular thermal volume of the lung and with radiographic findings of lung edema. A radiographic score of pulmonary edema may be used clinically to assess extravascular lung water in cardiac patients and in patients with adult respiratory distress syndrome.
Regional cerebral and cerebellar blood flows were studied by N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3- propanediamine 2 HCl (I-123 HIPDM) and single-photon emission computerized tomography (SPECT) in a patient with an ischemic lesion of the pons. An asymmetry of perfusion of the cerebellar hemispheres, normal on transmission computerized tomography scan, was demonstrated by SPECT studies in the early acute phase and confirmed 15 days after. This finding may be related to the interruption of the corticopontocerebellar pathways.
Sixteen patients with unilateral subcortical haemorrhagic or ischaemic stroke, confirmed by CT, were evaluated for the presence of aphasia and neglect. Compared with patients without neuropsychological deficits, left brain-damaged aphasic and right brain-damaged neglect patients showed a significantly greater reduction of cortical perfusion on N,N,N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1,3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerized tomography (SPECT). These results suggest that major cortical derangement is the crucial factor for the appearance of aphasia or neglect after a subcortical stroke. These remote effects, which are related to the size of the subcortical lesion, are interpreted in terms of interruption of neural connections (diaschisis).