L-hexamethylpropylene Amine Oxime Research Articles

Hyperglycaemia does not increase perfusion deficits after focal cerebral ischaemia in male Wistar rats.

Background:Hyperglycaemia is associated with a worse outcome in acute ischaemic stroke patients; yet the pathophysiological mechanisms of hyperglycaemia-induced damage are poorly understood. We hypothesised that hyperglycaemia at the time of stroke onset exacerbates ischaemic brain damage by increasing the severity of the blood flow deficit.Methods:Adult, male Wistar rats were randomly assigned to receive vehicle or glucose solutions prior to permanent middle cerebral artery occlusion. Cerebral blood flow was assessed semi-quantitatively either 1 h after middle cerebral artery occlusion using 99mTc-D, L-hexamethylpropyleneamine oxime (99mTc-HMPAO) autoradiography or, in a separate study, using quantitative pseudo-continuous arterial spin labelling for 4 h after middle cerebral artery occlusion. Diffusion weighted imaging was performed alongside pseudo-continuous arterial spin labelling and acute lesion volumes calculated from apparent diffusion coefficient maps. Infarct volume was measured at 24 h using rapid acquisition with refocused echoes T2-weighted magnetic resonance imaging.Results:Glucose administration had no effect on the severity of ischaemia when assessed by either 99mTc-HMPAO autoradiography or pseudo-continuous arterial spin labelling perfusion imaging. In comparison to the vehicle group, apparent diffusion coefficient–derived lesion volume 2–4 h post-middle cerebral artery occlusion and infarct volume 24 h post-middle cerebral artery occlusion were significantly greater in the glucose group.Conclusions:Hyperglycaemia increased acute lesion and infarct volumes but there was no evidence that the acute blood flow deficit was exacerbated. The data reinforce the conclusion that the detrimental effects of hyperglycaemia are rapid, and that treatment of post-stroke hyperglycaemia in the acute period is essential but the mechanisms of hyperglycaemia-induced harm remain unclear.

Validation of the leukocyte labeling procedure with a new kit for the preparation of technetium-99m exametazime injection.

The labeling of leukocytes with technetium-99m (Tc)-HMPAO is a frequent procedure in our laboratory, which was first validated before initiation of clinical studies with the commercial kit of Tc-D,L-hexamethylpropylene amine oxime (Tc-D,L-HMPAO), available from 1988. Recently, a new kit of exametazime has been introduced, with a similar composition and clinical indications, but with some technical improvements. Validation of the labeling procedure with this new kit is proposed, including a comparison between both commercial kits. Requirements for validation were achieved successfully and a comparative study showed no statistically significant differences; nevertheless, labeling of leukocytes may be expected routinely with the new kit on account of its longer shelf-life and lower cost.

(99m)Tc-hexamethyl propyleneamine oxime brain perfusion single photon emission computed tomography in characterization of dementia: an initial experience in Indian clinical practice.

There is a growing health burden in developing countries due to recent trends of increasing incidence of neurodegenerative diseases. To reduce the healthcare cost and effective management of dementia illness, early diagnosis, accurate differentiation and their progression assessment is becoming crucially important. We are utilizing 99mTc-d, l-hexamethyl propyleneamine oxime (HMPAO) brain perfusion single photon emission computed tomography (SPECT) to characterize dementia on the basis of perfusion patterns and observed significant improvement in their management. Eleven patients (median age of 60 years range of 53-83 years) with clinical suspicion of dementia underwent 99mTc-HMPAO brain perfusion SPECT. SPECT-computed tomography acquisition done, data are reconstructed, reviewed in three view and further processed in “neurogam” to get voxel based analysis and the comparison with age based normal database and surface mapping. Final diagnosis was done with clinical correlation. Four patients are diagnosed as Alzheimer's disease, two as frontotemporal dementia, one as dementia of Lewy bodies, two as vascular dementia and two as pseudodementia. All imaging findings are well-correlated with clinical background. Brain perfusion SPECT with HMPAO was very helpful to us in characterizing the patients of dementia by its perfusion pattern.

Influence of radiolytic‐produced hydrogen peroxide on the stability of commercial kit 99mtechnetium‐exametazime preparation

99mTc-d,l-hexamethylpropylene amine oxime ((99m) Tc-d,l-HMPAO) is a widely used radiopharmaceutical that suffers from an inherent instability with a shelf life of 30 min that constrains its availability for clinical use. A protocol for improving the stability of the kit with minimal modification of manufacturer's instructions and no chemicals addition to the commercial formulation is proposed. The protocol is based on the displacement of the oxygen present in the preparation, preventing free radicals build up and free pertechnetate formation. Although the degradation of (99m) Tc-d,l-HMPAO cannot be explained solely by the radiolytic production of free radicals, it appears to be an important factor in the shelf stability of the complex.

Noninvasive MRI Measurement of CBF: Evaluating An Arterial Spin Labelling Sequence with 99mTc-HMPAO CBF Autoradiography in a Rat Stroke Model

Arterial spin labelling (ASL) is increasingly available for noninvasive cerebral blood flow (CBF) measurement in stroke research. Here, a pseudo-continuous ASL technique (pCASL) was evaluated against (99m)Tc-D, L-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) autoradiography in a rat stroke model. The (99m)Tc-HMPAO was injected (intravenously, 225 MBq) during pCASL acquisition. The pCASL and (99m)Tc-HMPAO autoradiography CBF measures, relative to the contralateral hemisphere, were in good agreement across the spectrum of flow values in normal and ischemic tissues. The pCASL-derived quantitative regional CBF values (contralateral: 157 to 177 mL/100 g per minute; ipsilateral: 9 to 104 mL/100 g per minute) were consistent with the literature values. The data show the potential utility of pCASL for CBF assessment in a rat stroke model.

The clinical utility of 99mTc-HMPAO SPECT in Fahr’s disease

Fahr's disease is a rare neurodegenerative syndrome, characterized by massive symmetrical intracerebral calcifications of the basal ganglia, dentate nuclei of the cerebellum, and the adjacent parenchyma. Computerized tomography (CT) is considerably more sensitive to detect these intracranial calcifications than other imaging modalities. The clinical, CT scan, and 99(m)Tc-D,L-hexamethylpropylene amine oxime (99(m)Tc-HMPAO) brain perfusion single-photon emission computerized tomography (SPECT) findings in a 42-year-old woman with Fahr's disease are reported, and the clinical utility of 99(m)Tc-HMPAO SPECT findings in Fahr's disease is discussed in this article. In conclusion, 99(m)Tc-HMPAO brain perfusion SPECT seems to be useful in the clinical approach to Fahr's disease, and may provide more specific and clinically relevant information when compared with anatomical imaging.

The nervous system in early HIV infection: a prospective study through 7 years

In this study 28 patients with early stage HIV infection (CD4 >280 x 10(6)/l) were subjected to yearly examinations of the nervous system up to 7 years in order to detect any deterioration. Clinical neurological as well as neuropsychological performance was evaluated. The patients also underwent yearly neurophysiological tests (digital EEG, visual evoked potentials, somatosensory evoked potentials, auditory evoked potentials P300 and electroneurography). Every other year, SPECT with (99m)Tc-D,L-hexamethylpropylene amine oxime and brain MRI were performed. Originally, 38 patients were included in the study but only the results of 28 patients who complied with three of more yearly check-ups are presented. The results of yearly investigations of cerebrospinal fluid (CSF) have been presented earlier [Eur J Neurol4 (1997) 1]. All the patients showed signs of HIV in the CSF. Yet, no major deterioration in the neurological, psychological performance, neurophysiological or neuroimaging examinations could be discerned.

Clinical value of 99mTc-HMPAO SPECT in depressed bipolar I patients

Regional cerebral blood flow was studied in 17 bipolar I depressed patients (DSM-IV criteria) with single photon emission computed tomography (SPECT). Visual analysis of images revealed no abnormality in eight patients and abnormal findings in nine patients. In the nine patients with abnormal findings, all showed regional decreases of the uptake of 99mTc- d, l-hexamethylpropylene amine oxime (HMPAO, four in the frontal region, two in the basal ganglia, and three in both the frontal region and the basal ganglia). The patients with visible SPECT abnormalities had significantly higher scores on the Hamilton Rating Scale for Depression (HDRS).

An efficient HPLC method for the analysis of isomeric purity of technetium-99m-exametazime and identity confirmation using LC–MS

99mTc-exametazime ( 99mTc-d,l-HMPAO, 99mTc-d,l-hexamethylpropyleneamine oxime) is a neutral rather unstable complex of short-lived 99mTc ( t 1/2=6 h) with the d,l-isomer (mixture of d, d- and l, l-isomers) of a bis-amine bis-oxime tetraligand. It is widely used for measurement of regional cerebral perfusion in nuclear medicine. The meso-isomer ( d, l-form) should not be present in a preparation as it is not retained in brain and thus does not provide clinically useful information. Meso-HMPAO is removed from the ligand during the synthesis procedure by repeated recrystallization, but can still be present as impurity in d,l-isomer. Due to the lack of a suitable chromatographic method for analysis of the isomeric purity of 99mTc-exametazime preparations, United States Pharmacopoeia 25 (USP 25) prescribes a biological test in rats for quality control purpose. In this study, we developed a suitable high-performance liquid chromatography (HPLC) method which allows to demonstrate the relative amounts of d,l- and meso-isomer in 99mTc-exametazime and so obviates the need for a biodistribution test in animals as part of the quality control. Due to the low concentrations in which 99mTc-d,l-HMPAO is obtained (typically 2–6 ng/ml), confirmation of the identity of 99mTc-d,l-HMPAO in the monograph of the European Pharmacopoeia is now performed only indirectly by TLC and assessment of its retention time on RP-HPLC. To investigate the potential of radio-LC–MS for assessment of the identity of 99mTc-exametazime, 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO prepared using a Tc-rich eluate were analyzed using a radio-LC–MS system equipped with a time-of-flight mass spectrometer with electrospray ionization. The main peak in the radiometric channel coincided with the molecular ion mass of 99mTc-d,l-HMPAO in the mass spectrometer channel and the measured accurate mass differed only by 0.26 ppm from the theoretical mass. The identity of 99mTc-meso-HMPAO was also confirmed. Thus, radio-LC–MS allowed to obtain strong evidence for the structure of 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO at nanomolar concentration. It is concluded that radio-LC–MS can become a sensitive aid in quality control of “no carrier added” radiopharmaceutical preparations.

Reduced frontotemporal perfusion in psychopathic personality

Several brain-imaging studies have found associations between aberrant functioning in the frontal and temporal lobes and violent offending. We have previously reported decreased frontotemporal perfusion unrelated to psychosis, substance abuse, or current medication in 21 violent offenders. In the present study, we compared the regional cerebral blood flow (rCBF) in a new group of 32 violent offenders to scores on the Psychopathy Checklist-Revised (PCL-R), which rates two aspects of psychopathy: disturbed interpersonal attitudes (Factor 1) and impulsive antisocial behavior (Factor 2). A recently proposed model has split Factor 1 into a new Factor 1 (deceitful interpersonal style), a new Factor 2 (affective unresponsiveness), and a Factor 3, which approximately corresponds to the old Factor 2. The rCBF was assessed by single-photon emission computed tomography (SPECT) with technetium-99m- d, l-hexamethylpropyleneamine oxime (HMPAO) in regions of interest (ROIs) placed in accordance with fusioned magnetic resonance images (MRI) and SPECT scans. Significant negative correlations were found between interpersonal features of psychopathy (the old and especially the new Factor 1) and the frontal and temporal perfusion. The two most clearly associated ROIs were the head of the caudate nuclei and the hippocampi. These findings in a group of violent offenders living under the same conditions, which reduced the number of state-related confounders, add to the evidence indicating that aberrant frontotemporal activity may be a factor in violent behavior.

Regional cerebral blood flow as assessed by principal component analysis and 99mTc-HMPAO SPET in healthy subjects at rest: normal distribution and effect of age and gender

The increasing implementation of standardisation techniques in brain research and clinical diagnosis has highlighted the importance of reliable baseline data from normal control subjects for inter-subject analysis. In this context, knowledge of the regional cerebral blood flow (rCBF) distribution in normal ageing is a factor of the utmost importance. In the present study, rCBF was investigated in 50 healthy volunteers (25 men, 25 women), aged 31-78 years, who were examined at rest by means of single-photon emission tomography (SPET) using technetium-99m d, l-hexamethylpropylene amine oxime (HMPAO). After normalising the CBF data, 27 left and 27 right volumes of interest (VOIs) were selected and automatically outlined by standardisation software (computerised brain atlas). The heavy load of flow data thus obtained was reduced in number and grouped in factors by means of principal component analysis (PCA). PCA extracted 12 components explaining 81% of the variance and including the vast majority of cortical and subcortical regions. Analysis of variance and regression analyses were performed for rCBF, age and gender before PCA was applied and subsequently for each single extracted factor. There was a significantly higher CBF on the right side than on the left side ( P<0.001). In the overall analysis, a significant decrease was found in CBF ( P=0.05) with increasing age, and this decrease was particularly evident in the left hemisphere ( P=0.006). When gender was specifically analysed, CBF was found to decrease significantly with increasing age in females ( P=0.037) but not in males. Furthermore, a significant decrease in rCBF with increasing age was found in the brain vertex ( P=0.05), left frontotemporal cortex ( P=0.012) and temporocingulate cortex ( P=0.003). By contrast, relative rCBF in central structures increased with age ( P=0.001). The ability of standardisation software and PCA to identify functionally connected brain regions might contribute to a better understanding of the relationships between rCBF at rest, anatomically defined brain structures, ageing and gender.

Astrocytes as a predominant cellular site of (99m)Tc-HMPAO retention.

Technetium-99m-d,l-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) retention in the brain monitored by single photon emission computed tomography (SPECT) is currently used as a marker of cerebral blood flow. The purported mechanism by which (99m)Tc-HMPAO accumulates in the brain is through its intracellular conversion from a lipophilic form to more hydrophilic derivatives within the brain parenchyma. The issue of the contribution of different cell types on (99m)Tc-HMPAO retention was investigated in vitro by studying the accumulation of (99m)Tc-HMPAO in primary cultures of mouse cortical astrocytes and neurons. Results show that (99m)Tc-HMPAO retention predominates in astrocytes over neurons by a factor of approximately 2.5 (0.26 +/- 0.05 vs. 0.095 +/- 0.042 fmol/mg protein after 120 minutes, respectively). Diethyl maleate (60 micromol/L), ethacrynic acid (1 mmol/L) and buthionine sulfoximine (1 mmol/L), 3 agents which significantly reduced glutathione levels also decreased (99m)Tc-HMPAO retention in both astrocytes (29%, 3%, and 46% of control, respectively) and neurons (69%, 11% and 63% of control). Decrease did not always correlate with glutathione levels, however, which suggests that other factors could be involved. The possibility that cell energy status determines (99m)Tc-HMPAO retention was also assessed. Agents that activate (glutamate, azide) or inhibit (cytochalasin B) glucose utilization in astrocytes, as measured by the (3)H-2-deoxyglucose method, were without effect on (99m)Tc-HMPAO retention. In conclusion, the data presented indicate that astrocytes may constitute a prominent site of (99m)Tc-HMPAO retention and most likely contribute significantly to the SPECT signal. In addition, the data also suggest that specific alterations in glial cell metabolism could explain flow-independent changes in (99m)Tc-HMPAO retention in the brain as observed by SPECT in some pathologies.

99mTc-HMPAO as a tracer of cerebral blood flow in newborn infants.

Studies on the kinetics of 99mTc-D,L-hexamethylpropylene amine oxime (99mTc-HMPAO) in adults have shown that it is not an ideal tracer of CBF because it underestimates high-flow areas. Knowledge of the kinetics of the tracer is important in evaluating the studies. The kinetics of 99mTc-HMPAO in infants may be different from that in adults, therefore, we examined the cerebral uptake and retention of 99mTc-HMPAO in neonates and estimated the degree of brain-to-blood back diffusion by comparing corresponding 133Xe flow images and 99mTc-HMPAO distribution images. In addition, we measured the urinary excretion of 99mTc-HMPAO. Regional CBF was measured using a mobile brain-dedicated, fast-rotating, four-head multidetector system specially designed for neonatal studies. Tracers were 99mTc-HMPAO (4 MBq/kg) and 133Xe (500 MBq/kg). Cerebral uptake and leak-out of 99mTc-HMPAO were measured by a single scintillation crystal placed over the frontoparietal part of the infant's head. The cerebral retention of 99mTc-HMPAO was analyzed in 50 infants. The mean gestational age and birth weight (95% confidence interval) were 34.4 weeks (32.2-35.7) and 2,326 g (1,954-2,995), respectively. The cerebral uptake of 99mTc-HMPAO was examined in 16 of the 50 infants, and activity during 24 h was monitored in five. In 11 infants, corresponding 133Xe studies were performed. Urinary excretion was studied in 12 infants. The maximal activity in the brain was reached 90s after i.v. injection and was 104% (98-111) of the stable level, which was reached approximately 3 min after the injection. The decay corrected leakout of the tracer during the following 24 h was 1.0% (0.4-1.5) per hour. The cerebral retention was calculated at 6.8% (6.1-7.6), highest in the group of ictal studies and lowest in premature infants with intracranial hemorrhage. The mean value of the fixation/clearance ratio alpha was estimated at 3.4 (2.8-4.4). The mean urinary excretion over 24 h was 19.5% (11.4-27.7) and was significantly related to renal function as indicated by serum urea (p = 0.02 r2 = 0.55). A four-compartment model describing the kinetics of 99mTc-HMPAO is shown to be valid in neonates. The cerebral retention of the tracer is higher in neonates because of higher extraction and lower initial back diffusion from brain to blood. In linearizing 99mTc-HMPAO distribution images, a smaller correction is necessary, and we propose a value of the correction factor of 3.4. In this way, 99mTc-HMPAO is a more reliable tracer of the distribution of CBF in neonates compared with adults. The urinary excretion is significantly reduced compared with adults, and the radiation dose to the bladder wall is reduced. The effective dose is 0.3 mSv/MBq/kg.

Chronic osteomyelitis: diagnosis with tech netium-99m-d,l-hexamethylpropylene amine oxime labelled leucocytes

To evaluate the diagnostic value of technetium-99m d, l-hexamethylpropylene amine oxime (HMPAO) labelled leucocytes in combination with a 99mTc-methylene diphosphonate (MDP) bone scan in the detection of chronic osteomyelitis, we retrospectively reviewed 55 patients. Prior to the 99mTc-d,l-HMPAO labelled leucocyte scan, all patients underwent a 99mTc-MDP bone scan. The correct diagnosis was confirmed by long-term clinical follow-up (n=29) or by bacteriological cultures (n=26). We found an overall sensitivity of 94%, a specificity of 91% and an accuracy of 92% for 99mTc-d,l-HMPAO labelled leucocyte scintigraphy in the diagnosis of chronic osteomyelitis. When the patients were divided into three groups according to the location of the infection, our study results showed a sensitivity and specificity for the central location (containing active bone marrow) of 94% and 100% respectively; for the peripheral location (hands and feet) both parameters were 100%, and for the middle location (all sites between the central and the peripheral location) the values were 92% and 81% respectively. Specificity and accuracy were significantly lower in the middle location than in the central and peripheral locations. The results of our study confirm that a 99mTc-d,l-HMPAO labelled leucocyte scan in combination with an 99mTc-MDP bone scan is a reliable way to diagnose chronic osteomyelitis, except for vertebral osteomyelitis.

Vascular risk factors, atherosclerosis, cerebral white matter lesions and cerebral perfusion in a population-based study.

We studied risk factors for cerebral vascular disease (blood pressure and hypertension, factor VIIc, factor VIIIc, fibrinogen), indicators of atherosclerosis (intima-media thickness and plaques in the carotid artery) and cerebral white matter lesions in relation to regional cerebral blood flow (rCBF) in 60 persons (aged 65-85 years) recruited from a population-based study. rCBF was assessed with single-photon emission tomography using technetium-99m d, l-hexamethylpropylene amine oxime (99mTc-HMPAO). Statistical analysis was performed with multiple linear regression with adjustment for age, sex and ventricle-to-brain ratio. A significant positive association was found between systolic and diastolic blood pressure and temporo-parietal rCBF. In analysis with quartiles of the distribution, we found a threshold effect for the relation of low diastolic blood pressure (</=60 mmHg) and low temporo-parietal rCBF. Levels of plasma fibrinogen were inversely related to parietal rCBF, with a threshold effect of high fibrinogen levels (>3.2 g/l) and low rCBF. Increased atherosclerosis was related to low rCBF in all cortical regions, but these associations were not significant. No consistent relation was observed between severity of cerebral white matter lesions and rCBF. Our results may have implications for blood pressure control in the elderly population.

A comparative study of 99Tcm-d,l-HMPAO and 99Tcm-d,l-CBPAO as leukocyte-labelling agents

An attempt was made to use 99Tcm-d,l-cyclobutylpropylene amine oxime (99Tcm-d,l-CBPAO) to label leukocytes. The radiochemical purity of 99Tcm-d,l-CBPAO, labelling efficiency of leukocytes, cell viability of labelled leukocytes and stability of 99Tcm-d,l-CBPAO-labelled leukocytes were calculated. In comparison with the commercial cell-labelling agent 99Tcm-d,l-hexamethylpropylene amine oxime (99Tcm-d,l-HMPAO), (1) the radiochemical purity of 99Tcm-d,l-CBPAO was higher than that of 99Tcm-d,l-HMPAO immediately after and 1, 2, 4, 6, 8 and 24 h after 99Tcm labelling; (2) the labelling efficiency of 99Tcm-d,l-CBPAO-labelled leukocytes was lower than that of 99Tcm-d,l-HMPAO; (3) the viability of labelled white blood cells was high for both agents; and (4) the stability of 99Tcm-d,l-CBPAO-labelled leukocytes was better than that of 99Tcm-d,l-HMPAO after 1, 2, 4, 6, 8 and 24 h. In conclusion, although the labelling efficiency of 99Tcm-d,l-CBPAO is lower, it is more stable than 99Tcm-d,l-HMPAO and provides greater stability of 99Tcm-d,l-CBPAO-labelled leukocytes. Therefore, 99Tcm-d,l-CBPAO has the potential to replace 99Tcm-d,l-HMPAO as a commercial leukocyte-labelling agent.

Diagnostic value of 99Tcm-d,l-HMPAO-labelled leukocyte scintigraphy in the detection of vascular graft infections.

Prosthetic vascular graft infection is a relatively uncommon complication of peripheral vascular surgery. We retrospectively analysed technetium-99m-d,l-hexamethylpropylene amine oxime (99Tcm-d,l-HMPAO) labelled leukocyte scans of 21 patients with a suspected vascular graft infection. Operative findings, bacteriological cultures, radiological findings or clinical follow-up were used to confirm the diagnosis. We found eight true-positive and six true-negative cases. There were no false-positive scintigraphic diagnoses. The false-negative rate was 33% (n = 7). Our results show a sensitivity of 53%, a specificity of 100% and an accuracy of 66%. The conclusion is that a negative 99Tcm-d,l-HMPAO-labelled leukocyte scan is of limited value in ruling out a vascular graft infection. A combination of computed tomography (CT-scan) and a 99Tcm-d,l-HMPAO-labelled leukocyte scan is probably the most efficient way of diagnosing a vascular graft infection.

Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects.

Relative regional cerebral blood flow (rrCBF) was measured by single-photon emission tomography (SPET), using technetium-99m-d,l-hexamethylpropylene amine oxime (HMPAO) as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq 99mTc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3-12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of pathophysiological and prognostic importance in NPH.

Development of ROTOP-NEUROSPECT – a Tc-99m-Kit for Evaluation of Regional Cerebral Blood-Flow

Technetium-99m-d,l-hexamethylpropylene amine oxime (Tc-99m-HMPAO) has been developed in our Institute in order to meet the demand of GDR clinicians for a radiopharmaceutical, which allows the examination of regional cerebral blood-flow by SPECT. The present paper informs on synthesis and 13C NMR spectroscopic identification of the ligand d,l-HMPAO as well as its labelling by reconstitution of a sterile, freeze-dried mixture containing d,l-HMPAO, stannous chloride, and sodium chloride with Tc-99m-pertechnetate eluate. Labelling efficiency (more than 90%, the lipophilic component 80–90%) and pattern of products were estimated using tlc and paper chromatography with a combination of three solvent systems. Quality control of the freeze-dried formulation includes methods for quantitative determination of the ligand and of stannous chloride. The ability of Tc-99m-HMPAO to be localized in brain was quantified in rats by organ distribution with time and by autoradiography, showing both high initial uptake, and bl...