Tc-99m HMPAO Research Articles

Biodistribution study and identification of inflammatory sites using nanocapsules labeled with 99mTc–HMPAO

To evaluate the ability of polymeric nanocapsules (NCs) radiolabeled with technetium-99m D,L-hexamethylpropyleneamine oxime (Tc-HMPAO) to identify inflammatory process in an experimental model. NCs were prepared by interfacial deposition of preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by a solvent displacement. The size and homogeneity, and zeta potential of the NC preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. The NCs radiolabeled with Tc-HMPAO were administered intravenously to Wistar male rats bearing a focal inflammation induced by subplantar injection of carrageenan in the right foot. At preestablished time intervals, the animals were anesthetized, tissues were removed and radioactivity was determined using an automatic scintillation apparatus. The average diameter calculated by photon correlation spectroscopy varied from 216 to 323 nm. The biodistribution studies showed a greater uptake of the PEG surface-modified Tc-HMPAO-NC by the inflamed paws when compared with the respective controls. There was no significant difference in the uptake of conventional Tc-HMPAO-NC and of free Tc-HMPAO by inflamed and control paws. These results indicate that the PLA-PEG Tc-NC showed a higher uptake in inflammation compared with free complex and may be useful as a radiotracer to identify these foci.

Frontal Cerebral Blood Flow Changes after Hormone Replacement Therapy in Depressed Postmenopausal Women

We investigated the effects of hormone replacement therapy (HRT) on frontal cerebral blood flow (CBF), depressive symptoms, and cognitive function in depressed postmenopausal women. Fourteen postmenopausal women with depressive symptoms underwent HRT, and seven controls not undergoing HRT were studied. We evaluated frontal CBF, expressed as frontal/cerebellum (F/C) ratio, using Tc-99m hexamethyl propylene amine oxime single photon emission computed tomography (Tc-99m HMPAO SPECT), cognitive function using the Mini-Mental Status Examination (MMSE), and depression using the HAD (Hospital Anxiety and Depression) scale. All studies were carried out at initial status and after 9 months. Single photon emission computed tomography was performed at rest and at activation during the Wisconsin Card Sorting Test (WCST). Initial frontal CBF was not different between groups. After 9 months, resting frontal CBF was similar between groups. However, activated frontal CBF was significantly higher in the HRT group than in controls (F/C ratio: 0.924+/-0.04 versus 0.853+/-0.05, P=0.007). Furthermore, the increase in the activated F/C ratio was inversely associated with years since menopause. Mini-Mental Status Examination scores improved after HRT, but depression scores did not. Hormone replacement therapy improved frontal CBF and cognitive function but not depression in postmenopausal women. The changes in frontal CBF were detected only during WCST activation and were most apparent during early postmenopausal years.

Differences of TC-99M HMPAO spect imaging in the early stage of subcortical vascular dementia compared with Alzheimer's disease

Differences of TC-99M HMPAO spect imaging in the early stage of subcortical vascular dementia compared with Alzheimer's disease

Dopamine Transporter SPECT/CT and Perfusion Brain SPECT Imaging in Idiopathic Basal Ganglia Calcinosis

A case of idiopathic basal ganglia calcification in a 56-year-old woman with parkinsonism and cognitive impairment is described. The nigrostriatal dopaminergic pathway and regional cerebral blood flow were evaluated using dopamine transporter (DAT) brain single photon emission tomography combined with a low-dose x-ray computerized tomography transmission (hybrid SPECT/CT) and Tc-99m HMPAO brain perfusion SPECT study, respectively. DAT SPECT/CT imaging revealed a reduction in DAT binding in both striatum regions coinciding with bilateral calcifications in the basal ganglia. Brain perfusion scan showed hypoperfusion in basal ganglia regions, posterior parietal cortex bilaterally, left frontopolar and dorsolateral prefrontal cortex, and left temporal lobe. These findings correlated well with the clinical condition of the patient. Mineralization may play a critical role in the pathogenesis of neuronal degeneration. Cortical perfusion changes in patients may better explain the patient's altered cognitive and motor functions.

A new quantitative 99mTc HMPAO brain SPECT analysis in Alzheimer's Disease (AD) and Lewy bodies Dementia (LBD) differential diagnosis

A new quantitative 99mTc HMPAO brain SPECT analysis in Alzheimer's Disease (AD) and Lewy bodies Dementia (LBD) differential diagnosis

99mTc HMPAO SPECT prediction of conversion from mild cognitive impairment to Alzheimer's disease

99mTc HMPAO SPECT prediction of conversion from mild cognitive impairment to Alzheimer's disease

99mTc HMPAO SPECT prediction of conversion from mild cognitive impairment to Alzheimer's disease

D. P. Devanand, M.D., Ronald L. Van Heertum, M.D., Lawrence S. Kegeles, M.D., Ph.D., Xinhua Liu, Ph.D., Zong Hao Jin, Gnanavalli Pradhaban, M.B.B.S., Henry Rusinek, Ph.D., Mali Pratap, M.B.B.S., Gregory H. Pelton, M.D., Isak Prohovnik, Ph.D., Yaakov Stern, Ph.D., J. John Mann, M.D., and Ramin Parsey, M.D., Ph.D. Divisions of Geriatric Psychiatry and Molecular Imaging, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University; the Gertrude H. Sergievsky Center and the Departments of Neurology and Radiology, College of Physicians and Surgeons, Columbia University and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; New York University Medical Center, New York; and the Departments of Psychiatry and Radiology, Mount Sinai Medical Center, New York, NY

A new quantitative 99mTc HMPAO Brain SPECT analysis in Alzheimer's Disease (AD) and Lewy bodies Dementia (LBD) differential diagnosis

A new quantitative 99mTc HMPAO Brain SPECT analysis in Alzheimer's Disease (AD) and Lewy bodies Dementia (LBD) differential diagnosis

Tomographic measurements of regional cerebral blood flow in progressive supranuclear palsy and Parkinson's disease.

Intellectual changes observed in progressive supranuclear palsy (PSP) are sometimes seen with lesser intensity in Parkinson's disease (PD). Cognitive impairment of PSP has been attributed to a frontal lobe dysfunction explaining the frontal cortex hypometabolism detected by PET. To establish whether this frontal hypometabolism is more pronounced in PSP than in PD, we compared frontal and temporo-parietal cerebral blood flow (CBF) indexes studied by SPECT using Tc99m HmPAO in 18 PSP, 18 PD and 8 control subjects. For each patient neuropsychological performances were also assessed. A significant left frontal hypoperfusion was observed in PSP (mean index value: 0.78 +/- 0.03, p < 0.01) and PD (0.78 +/- 0.04, p < 0.05) as compared to controls (0.84 +/- 0.03), whereas there was no difference between PSP and PD. No correlation was discovered between neuropsychological performances and frontal cortical index changes. This frontal uptake reduction of Tc99m HmPAO in PSP and PD could result from a disconnection phenomenon secondary to subcortical lesions. In both groups mean frontal indexes showed only a left frontal hypoperfusion suggesting that subcortical structures might be asymmetrically involved in early stages of the diseases. The lack of difference for indexe values between PSP and PD might be explained by the difference between the mean disease duration: 4.3 years for the PSP and 7.8 years for the PD. It might also suggest that frontal CBF reduction exists in the same proportions in PD and PSP, but at a later stage in the former case.

Tc99m HM-PAO single photon emission computed tomography in temporal lobe epilepsy

We present the results of single photon emission computed tomography (SPECT) in 40 patients with temporal lobe epilepsy and normal computed transmission tomography (CT). Abnormalities of regional cerebral blood flow were found in 26 patients. There was focal hypoperfusion alone in 14, focal hyperperfusion alone in 6, and both types of abnormality in 6. In 4 patients there were bilateral abnormalities. Repeat SPECT showed persistence of interictal hyperperfusion in 5/12 patients. There were no significant correlations between SPECT findings and clinical parameters, and no relation between the persistence of interictal hyperperfusion and time since last seizure or seizure frequency. Where SPECT and multiple surface EEG recordings were both lateralising, agreement between them was good. The results of this study support the usefulness of HMPAO SPECT in detecting lateralising abnormalities in temporal lobe epilepsy. Interictal hyperperfusion may be commoner than previous publications suggest, and may be persistent in some cases.

Relative hyperperfusion by SPECT in a family with a presenilin 1 (T245P) mutation

Clinical characteristics of autosomal dominant Alzheimer's disease often differ clinically from sporadic disease with the onset of seizures, spasticity and myoclonus early in the disease course. Similarly imaging characteristics may also differ. We report the findings of relative hyperperfusion by Tc-99m HMPAO SPECT in the medial orbitofrontal cortex and anterior temporal lobe in four affected family members carrying a presenilin 1 mutation. SPECT of the four individuals was compared to an age-matched normal database. We speculate that the findings of relative medial orbitofrontal and anterior temporal lobe hyperperfusion may be a marker of early onset Alzheimer's disease in this family.

Tc-99m HMPAO Brain SPECT Imaging in Children With Acute Cerebellar Ataxia

We prospectively evaluated consecutive cases of acute cerebellar ataxia in children to identify brain perfusion SPECT features associated with acute cerebellar ataxia and to correlate the brain SPECT findings to clinical severity and prognosis. Among the 10 consecutive children with acute cerebellar ataxia, 7 had abnormal Tc-99m HMPAO brain SPECT findings (4 cerebellar hypoperfusion, 5 unilateral cortical and/or subcortical hypoperfusion, and 1 unilateral cortical hyperperfusion), in contrast to no abnormalities disclosed by CT or MR imagings. Furthermore, the extent of brain perfusion SPECT abnormalities correlated significantly with the clinical severity and the recovery time of cerebellar ataxia. Sixty percent of children with acute cerebellar ataxia had cortical and/or subcortical involvement, which implied the wider involvement of acute cerebellar ataxia than what has been thought. The present data suggest that Tc-99m HMPAO brain SPECT is a sensitive modality for providing prognostic information in childhood acute cerebellar ataxia.

Abstract 5257: Priming with Angiopoietin-1 Augments Angiogenic Potential of Peripheral Blood Stem Cells Mobilized with Granulocyte-Colony Stimulating Factor

Background: We introduce the concept of ‘priming’ mobilized peripheral blood stem cells( mob -PBSCs) with G-CSF using Angiopoietin-1(Ang-1). Methods and Results: Ang-1 was administered as a priming agent because it was found that mob PBSCs highly express Tie2, Ang-1 receptor [19.2±3% vs. 1.2±0.2%, p&lt;0.01 for mob PBSCs vs PBMCs]. We investigated whether the effect of Ang-1 on mob PBSCs differentiation is mediated via the transcriptional regulation of ets-1. The gene expression of ets-1 increased in a time dependent manner after Ang-1 stimulation(400ng/ml) in mob PBSCs. Compared with vehicle, treatment with Ang-1 for 4 hours resulted in stronger expression of endothelial markers, such as, CD31 and VE-cadherin, which were significantly reduced with antisense ets-1 oligodeoxynucleotides(ODN). These results were also confirmed at the protein level by FACS analysis. We postulated that integrins that contain an ets-1 binding motif in their promoter region may be activated by Ang-1, such as α4β1 and α5β1 integrins. RT-PCR showed increased mRNA expression of α4, α5, and β1 integrins after Ang-1 stimulation, and its attenuation after transfection with antisense ets-1 ODN. These results were also confirmed at the protein level by FACS analysis. To correlate these findings with functional changes in mob PBSCs, we performed in vitro adhesion assays. Ang-1 stimulation increased mob PBSCs adhesion to HUVECs and fibronectin, while pretreatment with anti-hTie2 or anti-integrin antibody prior to Ang-1 stimulation abrogated these results. And, we checked the effect of Ang-1 in vivo model. mob PBSCs were obtained from rabbit and primed with COMP-Ang1(400ng/ml) for 4 hours. mob PBSCs were labeled with Tc-99m HMPAO and were injected into a central artery of rabbit ear. mob PBSC engraftment was quantified by the ratio of whole rabbit ear radioactivity over total infused mob PBSC radioactivity. In contrast, cells primed with COMP-Ang1 showed markedly increased engraftment by 53±33%( p &lt;0.05). Finally, mob PBSCs primed with Ang-1 enhanced neovascularization in a nude mouse hindlimb ischemia model. Conclusion: These results suggest that mob PBSCs priming with Ang-1 may enhance the efficacy of transplanted mob PBSCs in terms of increasing neovascularization in ischemic tissue.

Valoración del flujo sanguíneo cerebral en pacientes con trastornos de la conducta alimentaria en fase aguda mediante SPECT con HMPAO-Tc99m

Objective. To assess the status of cerebral perfusion in patients with eating disorders (ED) in the acute phase of the disease. Materials and methods. Seventeen patients, with a mean age of 22 years, diagnosed with ED according to DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) criteria and under close clinical monitoring were studied in the initial acute phase of their disease. Brain SPECT with 15 mCi of Tc99m HMPAO was performed on all patients and assessed using visual and semi-quantitative analysis. The latter was carried out by obtaining left/right indices in sixteen symmetrical 5 ¥ 5 pixel regions of interest (ROI) in three transverse slices, one below the cantho-meatal line and two above, at 2 and 5 cm, respectively. Results. Visual analysis showed hypoperfusion of the anteroinferior region of the left temporal lobe in 7/17 patients, and in the homonymous region of the right temporal lobe in 1/17. Semi-quantitative analysis did not show statistically significant differences in the slices above the cantho-meatal line when the means of the asymmetry indices were compared between the anterior (frontal), middle (temporal and parietal) and posterior (occipital) regions of each slice, obtaining values ranging between 0.99 ± 0.05 and 1.02 ± 0.03. However, in the lowest slice, the anterior (temporal) region showed a mean asymmetry value of 0.89 ± 0.15, and on comparing it with the mean of the asymmetry indices of the posterior region (cerebellum), it showed a statistically significant difference (p < 0.05). Conclusion. Patients with ED frequently show hypoperfusion of the anteroinferior region of the temporal lobe, predominantly in the left hemisphere, in the acute phase of the illness.

Assessment of cerebral blood flow in patients with eating disorders in the acute clinical phase using Tc99m-HMPAO SPECT

Objective To assess the status of cerebral perfusion in patients with eating disorders (ED) in the acute phase of the disease. Materials and methods Seventeen patients, with a mean age of 22 years, diagnosed with ED according to DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) criteria and under close clinical monitoring were studied in the initial acute phase of their disease. Brain SPECT with 15 mCi of Tc99m HMPAO was performed on all patients and assessed using visual and semi-quantitative analysis. The latter was carried out by obtaining left/right indices in sixteen symmetrical 5 × 5 pixel regions of interest (ROI) in three transverse slices, one below the cantho-meatal line and two above, at 2 and 5 cm, respectively. Results Visual analysis showed hypoperfusion of the anteroinferior region of the left temporal lobe in 7/17 patients, and in the homonymous region of the right temporal lobe in 1/17. Semi-quantitative analysis did not show statistically significant differences in the slices above the cantho-meatal line when the means of the asymmetry indices were compared between the anterior (frontal), middle (temporal and parietal) and posterior (occipital) regions of each slice, obtaining values ranging between 0.99 ± 0.05 and 1.02 ± 0.03. However, in the lowest slice, the anterior (temporal) region showed a mean asymmetry value of 0.89 ± 0.15, and on comparing it with the mean of the asymmetry indices of the posterior region (cerebellum), it showed a statistically significant difference (p < 0.05). Conclusion Patients with ED frequently show hypoperfusion of the anteroinferior region of the temporal lobe, predominantly in the left hemisphere, in the acute phase of the illness.

P2-057: Regional cerebral blood flow using Tc-99m HMPAO SPECT in patients with mild cognitive impairment

P2-057: Regional cerebral blood flow using Tc-99m HMPAO SPECT in patients with mild cognitive impairment

Treatment responsive executive and behavioral dysfunction associated with Vitamin B12 deficiency*

Vitamin B12 deficiency can manifest with various neuropsychiatric symptoms. We report a case of an individual with vitamin B12 deficiency presenting with personality, emotional and behavioral changes. Neuropsychological tests revealed disproportionate disturbance of executive functions. Single photon emission tomography (Tc99m HMPAO) showed right fronto-temporo-parietal hypoperfusion. After vitamin B12 injections, the patient's executive and behavioral dysfunction disappeared and performance on neuropsychological tests was once again in the normal range.

Required time delay from 99mTc-HMPAO injection to SPECT data acquisition: healthy subjects and patients with rCBF pattern

Functional brain (99m)Tc-HMPAO single-photon emission computed tomography (SPECT) is a useful diagnostic tool for assessment of regional cerebral blood flow, particularly in dementia, cerebrovascular disease and epilepsy. Currently, the European and American Association of Nuclear Medicine Procedure Guidelines for Brain Perfusion SPET using (99m)Tc-labeled Radiopharmaceuticals recommend a time delay of 90 min between injection of (99m)Tc-HMPAO and data acquisition. This time delay is difficult to comply within the daily routine and present a problem, particularly with the elderly or demented patients. This study investigates in patients with perfusion deficits and in healthy subjects if the quality of the SPECT image is affected by lowering the time delay between (99m)Tc-HMPAO injection and data acquisition to 30 or 60 min. Thirty-seven healthy subjects (17 females; mean age 65; range 42-84 years) with normal cerebral blood flow distribution and 31 patients (17 females; mean age 67; range 38-84) with reduced rCBF distribution were included. Images were obtained with a three-headed Philips IRIX SPECT scanner with high-resolution collimators. The healthy subjects were scanned 30, 60 and 90 min after (99m)Tc-HMPAO injection, and the patients were scanned 30 and 90 or 60 and 90 min after (99m)Tc-HMPAO injection. For evaluation of differences between the images obtained at various time points after injection, two different methods were used. The z-map method was used to subtract images from each other prior to visual inspection. In addition, principal component analysis was used as a quantitative analysis of the similarity of the images. Visual inspection of the subtracted images (30 or 60 versus 90 min) revealed that there was no spatial bias. Quantitatively, the average proportion of the total variance explained by the first principal component was 99.5% (range 98.9-99.6) for the healthy subjects and 99.4% (range 98.5-99.8) for the patients. The time delay from injection of (99m)Tc-HMPAO to the start of the SPECT data acquisition can be reduced from 90 to 30 min without any significant impact on the quality of the acquired image.

Technetium-99m hexamethyl propylene amine oxime-labeled leukocyte scintigraphy at three different times in active ulcerative colitis: comparison with colonoscopy and clinico-biochemical parameters in the assessment of disease extension and severity

In this study, our objective was to define the usefulness of technetium-99m hexamethyl propylene amine oxime (Tc-99m HMPAO)-labeled leukocyte scintigraphy at three different time points in the assessment of disease extension and severity in patients with active ulcerative colitis (UC). Twenty-one consecutive patients (10 women, 11 men; mean age 42.4 +/- 12 years) with active UC were prospectively studied. All patients were diagnosed by colonoscopy and histopathology prior to inclusion. Scintigraphy was performed at 1 h, 2 h, and 4 h after Tc-99m HMPAO-labeled leukocyte injection. Clinic-biochemical activity score, total colonoscopic activity score, and total scintigraphic activity score at 1 h, 2 h, and 4 h were calculated for each patient. Sensitivity, specificity, and accuracy values of Tc-99m HMPAO-labeled leukocyte scintigraphy were calculated as follows, respectively: 1 h imaging 86%, 73%, and 83%; 2 h imaging 89%, 74%, and 86%; 4 h imaging 90%, 58%, and 83% in the detection of active inflammatory segments. Even though no statistically significant difference was found between 1 h, 2 h, and 4 h imaging with respect to the sensitivity, specificity of labeled leukocyte scintigraphy, the largest area under the curve value was found for 2 h imaging. Tc-99m HMPAO-labeled leukocyte scintigraphy has been found to be correlated well with colonoscopy in the assessment of both the extension and severity of UC. We recommend 2 h scintigraphic imaging because it provides the largest area under the curve value and decreases the number of false-positive results.

Technetium-99m HMPAO brain SPECT in autistic children and their families

The purpose of the study was to investigate perfusion patterns in autistic children (AC) and their families. Ten AC (9 boys, 1 girl; mean age: 6.9 ± 1.7 years) with autistic disorder defined by DSM-III-R criteria, five age-matched children (3 boys, 2 girls) as a control group, and the immediate family members of eight AC (8 mothers, 8 fathers, 7 siblings; mean ages: 39 ± 4 years, 36 ± 5 years and 13 ± 5 years, respectively) were included in the study. Age- and sex-matched control groups for both the parents and the siblings were also included in the study. Brain perfusion images were obtained 1 h after the intravenous injection of an adjusted dose of Tc-99m HMPAO to children and the adults. Visual and semiquantitative evaluations were performed. Hypoperfusion was seen in the right posterior parietal cortex in three AC, in bilateral parietal cortex in one AC, bilateral frontal cortex in two AC, left parietal and temporal cortex in one AC, and right parietal and temporal cortex in one AC. Asymmetric perfusion was observed in the caudate nucleus in four AC. In semiquantitative analyses, statistically significant hypoperfusion was found in the right inferior and superior frontal, left superior frontal, right parietal, right mesial temporal and right caudate nucleus. In parents of AC, significant hypoperfusion was noted in the right parietal and bilateral inferior frontal cortex. In siblings of AC, perfusion in the right frontal cortex, right nucleus caudate and left parietal cortex was significantly decreased. This preliminary study suggests the existence of regional brain perfusion alterations in frontal, temporal, and parietal cortex and in caudate nucleus in AC and in their first-degree family members.