Regional differences between <Superscript>99m</Superscript>Tc-ECD and <Superscript>99m</Superscript>Tc-HMPAO SPET in perfusion changes with age and gender in healthy adults

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether ^99mTc-HMPAO or ^99mTc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8±6.6 years) were assigned to ^99mTc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6±6.7 years) to ^99mTc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq ^99mTc-HMPAO or ^99mTc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether ^99mTc-HMPAO and ^99mTc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.     

Regional cerebral blood flow assessed with <Superscript>99m</Superscript>Tc-ECD SPET as a marker of progression of mild cognitive impairment to Alzheimer's disease

Patients diagnosed with mild cognitive impairment (MCI) have a higher risk of developing Alzheimer's disease (AD). However, not all such patients develop this kind of dementia. The purpose of this prospective study was to assess whether regional cerebral blood flow (rCBF) patterns measured with technetium-99m ethyl cysteinate dimer single-photon emission tomography (^99mTc-ECD SPET) in patients suffering from MCI are useful in predicting progression to AD. The study group comprised 42 patients who fulfilled MCI criteria according to the International Psychogeriatric Association and the Alzheimer's Disease Cooperative Study. rCBF was calculated in 16 regions of interest (ROIs). All patients were clinically assessed for 1–3 years. Twenty-one developed AD (group I) while the initial diagnosis of MCI was retained in the other 21 (group II). ROC curves were designed, and sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were determined for each ROI. Compared with group II (MCI), group I (AD) showed a significant reduction of relative blood flow (RBF), ranging from 7% to 10%, in the following areas: right and left prefrontal, right and left frontal, right and left parietal, right and left temporal, right and left frontoparietotemporal and left posterior lateral temporal. Left prefrontal, left frontal and left parietal areas showed sensitivities and specificities higher than 75% and areas below the ROC curve close to 80%. This study shows that RBF patterns in the right and left prefrontal, right and left frontal and left parietal areas are sensitive early markers of progression towards AD. Reduction of rCBF in the medial temporal and anterior lateral temporal cortex has no value as a predictor since it also occurs in patients with MCI who remain stable.     

Quantitative assessment of blood flow reserve using <Superscript>99m</Superscript>Tc-HMPAO in carotid stenosis

Dynamic imaging of the inflow of technetium-99m hexamethylpropylene amine oxime (HMPAO) to the brain has been proved to allow estimation of the hemispherical cerebral blood flow (CBF) using the Patlak plot. In this study, we compared the hemispherical CBF (in ml/min/100 g) of different patient groups. A total of 25 patients (comprising 13 with migraine and 12 scheduled for endarterectomy owing to angiographically confirmed severe stenosis of the internal carotid artery on at least one side) underwent baseline and acetazolamide 99mTc-HMPAO brain perfusion studies. In addition, acetazolamide 99mTc-HMPAO studies were performed in 12 healthy subjects (no baseline study was performed for ethical reasons.) Dynamic studies were acquired by means of a dual-detector gamma camera with a large field of view (HELIX, Elscint). Special difference images were created to make definition of the aortic arch and hemispherical brain regions easier and more reproducible. A semi-automatic method was developed to determine the transit time from the aorta to the brain, making the generation of the Patlak plot even more robust. The baseline CBF values did not significantly depend on the disease (P>0.1), whereas the CBF values obtained after acetazolamide provocation did do so (ANOVA, P<0.001). Patients suffering from migraine showed a significant increase in global CBF values after acetazolamide provocation (paired t test, P<0.05), but we could not find any effect of the provocation in patients awaiting carotid endarterectomy, indicating a lack of cerebrovascular reserve capacity. Comparison of the results of the acetazolamide study in patients and the control group revealed the CBF values to be significantly lower in patients with carotid stenosis (two-sample t-test, P<0.001), but not in those with migraine (P>0.1). In summary, using quantitative analysis of 99mTc-HMPAO brain studies we could objectively compare the CBF of patients suffering from different diseases. Especially the CBF values obtained after acetazolamide provocation permitted effective differentiation of disease states. The quantitative results may be of assistance in therapy planning, e.g. in selection of the correct operative technique.     

Automatic determination of brain perfusion index for measurement of cerebral blood flow using spectral analysis and <Superscript>99m</Superscript>Tc-HMPAO

Cerebral blood flow (CBF) can be non-invasively quantified using the brain perfusion index (BPI), determined from radionuclide angiographic data generated by technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO). We previously reported the use of a spectral analysis (SA) method using (99m)Tc-HMPAO to calculate the BPI. In this report, we demonstrate an automatic method for determining the optimal BPI value and compare the optimal BPI values with the absolute CBF values measured using H(2)(15)O positron emission tomography (PET). Bilateral cerebral hemispheres of 11 patients with various brain diseases were examined using (99m)Tc-HMPAO. In the automatic SA procedure, the radioactivity curve for the aortic arch ( C (a)) was shifted by 0-10 s. The radioactivity curve for the brain ( C (b)) was estimated using the shifted C (a), and the error value between the actually measured and the estimated C (b) (Err) was calculated. When the Err was at a minimum, the BPI value was defined as optimal BPI. The difference in BPI from the optimal BPI was calculated as |BPI - optimal BPI| / optimal BPIx100 (%). In all participants, an H(2)(15)O PET examination was also performed, and the BPI values were compared with the absolute CBF values measured using H(2)(15)O PET (mCBF(PET)). The difference between BPI and the optimal BPI increased significantly from 4.87%+/-1.69% to 18.38%+/-3.93% (mean+/-SD) when the Err value increased. The optimal BPI value ( y) was well correlated with the mCBF(PET) value ( x) ( y=0.21 x-0.0075, r=0.800). Our results suggest that this automatic SA method provides an accurate estimate of BPI that can be used for the quantification of CBF using (99m)Tc-HMPAO SA.     

<Superscript>99m</Superscript>Tc-HMPAO and <Superscript>99m</Superscript>Tc-ECD perform differently in typically hypoperfused areas in Alzheimer's disease

Ohne Zusammenfassung     

Required time delay from <Superscript>99m</Superscript>Tc-HMPAO injection to SPECT data acquisition: healthy subjects and patients with rCBF pattern

Purpose  Functional brain ^99mTc-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 ^99mTc-labeled Radiopharmaceuticals recommend a time delay of 90 min between injection of ^99mTc-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 ^99mTc-HMPAO injection and data acquisition to 30 or 60 min. Methods  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 ^99mTc-HMPAO injection, and the patients were scanned 30 and 90 or 60 and 90 min after ^99mTc-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. Results  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. Conclusion  The time delay from injection of ^99mTc-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.     

Simultaneous <Superscript>99m</Superscript>Tc/<Superscript>201</Superscript>Tl dual-isotope SPET with Monte Carlo-based down-scatter correction

In simultaneous technetium-99m/thallium-201 dual-isotope (DI) single-photon emission tomography (SPET), down-scatter of (99m)Tc photons contaminates the (201)Tl image, which leads to a decrease in lesion contrast and loss of quantitative accuracy. Correction for down-scatter can be achieved by first reconstructing the (99m)Tc activity distribution. Subsequently, the (99m)Tc down-scatter in the (201)Tl photopeak window is simulated and used for correction during iterative reconstruction of the (201)Tl image. In this work, the down-scatter projections are calculated using a dedicated Monte Carlo simulator which is able to efficiently model the detection of lead X-rays from the collimator. An anthropomorphic torso phantom with a cardiac insert with and without cold lesions was used for evaluation of the proposed method. Excellent agreement in lesion contrast and quantitative accuracy was found between the down-scatter corrected DI-SPET (201)Tl image and the virgin (i.e. separately acquired) (201)Tl image, in particular when the effects of lead X-rays were included. Compensation for the noise added by down-scatter to the (201)Tl image can be achieved by using a 15% lower dose of (99m)Tc, a 15% increase in scan time and a 12% increase in (201)Tl dose. In conclusion, the Monte Carlo-based down-scatter correction recovers lesion contrast and quantitative accuracy in DI-SPET (201)Tl images almost perfectly. In addition, degradations due to the added noise of down-scatter in simultaneous DI-SPET can be prevented by slight adaptations to the data acquisition protocol.     

Investigation into the mechanisms of vagus nerve stimulation for the treatment of intractable epilepsy,using <Superscript>99m</Superscript>Tc-HMPAO SPET brain images

Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21-39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250 MBq of (99m)Tc-HMPAO and a four-scan paradigm - two with and two without stimulation. The stimulation began at VNS current levels of 0.25 mA and was increased according to the limit of patients' tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500 micro s duration at 30 Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation.     

<Superscript>11</Superscript>C-acetate PET imaging of lung cancer: comparison with <Superscript>18</Superscript>F-FDG PET and <Superscript>99m</Superscript>Tc-MIBI SPET

Recently carbon-11 acetate (AC) positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of cancer that is negative on fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in lung cancer to determine whether this tracer is of potential value for tumour detection and characterisation, and to compare AC PET imaging with FDG PET and technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty-three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23 patients were also investigated with MIBI SPET. Dynamic images were acquired for 26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs) and/or tumour to non-tumour activity ratios (T/N) for each tumour were investigated at 10–20 min after AC administration, 40–60 min after administration of 185 MBq FDG and 15–45 min after administration of 555 MBq MIBI. Twenty lung cancers were resected surgically, and the degree of tracer uptake in the primary lesion was correlated with histopathological features (cell dedifferentiation and aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow clearance was observed. For the purpose of tumour identification, AC PET was inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower than that of FDG. However, AC PET was superior to FDG PET in the identification of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P<0.0001). A positive correlation was not observed between either AC or MIBI uptake and the degree of cell dedifferentiation in lung adenocarcinomas, whereas FDG uptake did correlate with the degree of cell dedifferentiation. In lung adenocarcinoma, there was a weak correlation between aggressiveness and FDG uptake, but no correlation was evident for AC and MIBI. In addition, a positive correlation was not observed between AC or MIBI uptake and postoperative recurrence in lung adenocarcinoma, whereas FDG uptake did correlate with postoperative recurrence. Thus, the greater the FDG uptake, the higher the malignant grade. In conclusion, for the purpose of tumour identification, AC PET was inferior to FDG PET but superior to MIBI SPET. Neither AC nor MIBI uptake reflects the malignant grade in lung adenocarcinoma, whereas FDG uptake does. AC PET is less diagnostically informative than FDG PET in patients with lung cancer. However, AC PET may play a complementary role in the identification of low-grade malignancies that are not FDG avid.     

<Superscript>11</Superscript>C-methionine uptake in cerebrovascular disease: A comparison with<Superscript>18</Superscript>F-FDG PET and<Superscript>99m</Superscript>Tc-HMPAO SPECT

OBJECTIVES: Carbon-11-L-methyl-methionine (11C-methionine) has been reported to be useful for evaluating brain tumors, but several other brain disorders have also shown signs of high methionine uptake. We retrospectively evaluated the significance of 11C-methionine uptake in cerebrovascular diseases, and also compared our results with those for 18F-FDG PET and 99mTc-HMPAO SPECT. METHODS: Seven patients, including 3 patients with a cerebral hematoma and 4 patients with a cerebral infarction, were examined. All 7 patients underwent both 11C-methionine PET and 99mTc-HMPAO SPECT, and 6 of them underwent 18F-FDG PET. RESULTS: A high 11C-methionine uptake was observed in all 3 patients with cerebral hematoma. Increased 99mTc-HMPAO uptake was observed in 2 out of 3 patients, and all 3 patients had decreased 18F-FDG uptake. Of 4 patients with a cerebral infarction, high 11C-methionine uptake was observed in 3. Increased 99mTc-HMPAO uptake was also observed in one patient, whereas 3 patients had decreased 18F-FDG uptake. CONCLUSIONS: We should keep in mind that high 11C-methionine uptake is frequently observed in cerebrovascular diseases. CVD should therefore be included in the differential diagnosis when encounting patients with a high 11C-methionine uptake.     

Questionnaire survey of hospitals in Saitama Prefecture regarding the shortage of <Superscript>99m</Superscript>Tc-labeled radiopharmaceuticals and <Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generators

Objective and methods  

A questionnaire survey was conducted at all 32 hospitals in Saitama Prefecture to investigate the current difficult situation in terms of nuclear medicine management in the face of the ^99mTc shortage due to insufficient supply, and 29 hospitals (90.6%) replied.     

<Superscript>111</Superscript>In-oxine and <Superscript>99m</Superscript>Tc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content

In cancer vaccination trials, antigen-loaded dendritic cells (DCs) are usually injected intradermally and are expected to rapidly move to a regional lymph node where antigen presentation should occur. In this study we investigated the influence of indium-111 oxine (111In) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelling on the motility and actin content of antigen-loaded DCs in parallel with in vivo migration in humans. Human autologous monocyte-derived DCs loaded with a tumour antigen were labelled with 111In (0.11, 0.37 or 0.74 MBq/10(7) DCs) or 99mTc-HMPAO (18.5 or 185 MBq/10(7) DCs). 111In labelling was much more stable than 99mTc-HMPAO labelling. Quantitative videomicroscopy showed that the mean distance of displacement of DCs increased in accordance with the 111In activity used for labelling. Monomeric (G) and filamentous (F) actin content of DCs evaluated by quantitative immunofluorescence demonstrated that the ratio of filamentous to globular actin content in labelled DCs increased significantly in accordance with the activity used for labelling with both tracers. Twelve patients enrolled in a phase I/II vaccination trial received injections of 10(7) antigen-loaded DCs labelled with either 0.74 MBq of 111In (group A, n=6/12) or 18.5 MBq of 99mTc-HMPAO (group B, n=6/12) in the proximal part of the legs, one intradermally on one side, one subcutaneously on the opposite side. In three of the six patients of each group, antigen-loaded DCs were incubated with monophosphoryl lipid A (MPL) just before the labelling, in order to initiate the maturation process (subgroup MPL+). Only one MPL+ patient of group A exhibited faint focal uptake in the inguinal region on the late images. Group B presented a more complex pattern of radioactivity distribution (early bladder activity without brain uptake) indicating that 99mTc-HMPAO is not a suitable radiopharmaceutical for labelling of loaded DCs. The activity cleared from DCs as a labelled molecule different from the lipophilic 99mTc-HMPAO. Only one of the six patients had nodular inguinal uptake on the intradermally injected side (DCs not incubated with MPL). In conclusion, the present study did not demonstrate migration of loaded labelled DCs from intradermal or subcutaneous sites of injection to regional lymph nodes. This provides an indication that a large proportion of antigen-loaded DCs, as used in current human trials for cancer therapy, may not reach regional lymph nodes.     

Comparison of whole-body <Superscript>18</Superscript>F-FDG PET, <Superscript>99m</Superscript>Tc-MIBI SPET,and post-therapeutic <Superscript>131</Superscript>I-Na scintigraphy in the detection of metastatic thyroid cancer

The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile (^99mTc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of ^99mTc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38–72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following ¹³¹I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and ^99mTc-MIBI SPET WBS at an interval of less than 1 week, followed by ¹³¹I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. ¹³¹I WBS was performed 3–5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, ²⁰¹Tl and ¹³¹I scans). FDG-PET, ^99mTc-MIBI SPET and post-therapeutic ¹³¹I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%), seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the six bone metastases (83.3%). FDG-PET and ^99mTc-MIBI SPET were positive in 17 (78.3%) and 14 (63.6%) of the 22 ¹³¹I-positive lesions, respectively, and also in nine (90.0%) and six (60.0%) of the ten ¹³¹I-negative lesions, respectively. Three of the five ¹³¹I-positive and FDG-PET-negative lesions were miliary type lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of FDG-PET with ^99mTc-MIBI SPET revealed concordant results in 24 lesions, and discordant results in eight lesions (seven with positive FDG-PET alone and one with positive ^99mTc-MIBI SPET alone). In conclusion: (a) even using whole-body SPET, FDG PET is superior to ^99mTc-MIBI in terms of ability to detect metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the previous studies could partly be due to increased serum TSH.     

Visualisation of the normal adrenals at SPET examination with <Superscript>111</Superscript>In-pentetreotide

On single-photon emission tomography (SPET) examinations with indium-111 pentetreotide, we have often observed a small "hot" spot close to the upper portion of the left kidney. While it was initially believed that this represented a tumour in the tail of the pancreas or in the left adrenal, we now understand that it represents normal adrenal uptake. Since the adrenals have not been described as normally visualised, this uptake may interfere with the interpretation of the examination. We have studied how often the normal adrenals are visualised at such examinations. One hundred consecutive clinical (111)In-pentetreotide examinations in adults including SPET of the abdomen and with normal findings were studied. All examinations with a hot spot attributable to the adrenals were, when available, compared with computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen performed on clinical grounds within 3 months before or at any time after the scintigraphy. In 11 patients both adrenals were visualised. In 27 patients only the left and in one only the right adrenal was visualised. CT or MRI examinations were available for comparison in 25 of these 39 patients. Two of these showed a pathological finding in the left adrenal. A conservative interpretation is that the normal adrenal is visualised on one or both sides in at least one-quarter of adults at SPET examination with (111)In-pentetreotide.     

Anatomically standardised <Superscript>99m</Superscript>Tc-ECD brain perfusion SPET allows accurate differentiation between healthy volunteers,multiple system atrophy and idiopathic Parkinson's disease

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders such as multiple system atrophy (MSA) is complicated by the presence of signs and symptoms common to both forms. The goal of this study was to re-evaluate the contribution of brain perfusion single-photon emission tomography (SPET) with anatomical standardisation and automated analysis in the differentiation of IPD and MSA. This was achieved by discriminant analysis in comparison with a large set of age- and gender-matched healthy volunteers. Technetium-99m ethyl cysteinate dimer SPET was performed on 140 subjects: 81 IPD patients (age 62.6+/-10.2 years; disease duration 11.0+/-6.4 years; 50 males/31 females), 15 MSA patients (61.5+/-9.2 years; disease duration 3.0+/-2.2 years; 9 males/6 females) and 44 age- and gender-matched healthy volunteers (age 59.2+/-11.9 years; 27 males/17 females). Patients were matched for severity (Hoehn and Yahr stage). Automated predefined volume of interest (VOI) analysis was carried out after anatomical standardisation. Stepwise discriminant analysis with cross-validation using the leave-one-out method was used to determine the subgroup of variables giving the highest accuracy for this differential diagnosis. Between MSA and IPD, the only regions with highly significant differences in uptake after Bonferroni correction were the putamen VOIs. Comparing MSA versus normals and IPD, with putamen VOI values as discriminating variables, cross-validated performance showed correct classification of MSA patients with a sensitivity of 73.3%, a specificity of 84% and an accuracy of 83.6%. Additional input from the right caudate head and the left prefrontal and left mesial temporal cortex allowed 100% discrimination even after cross-validation. Discrimination between the IPD group alone and healthy volunteers was accurate in 94% of the cases after cross-validation, with a sensitivity of 91.4% and a specificity of 100%. The three-group classification (MSA, IPD and healthy volunteers) resulted in an overall accuracy of 86% post hoc, with 98% of normals, 78% of IPD and 93% of MSA correctly classified. These values were slightly lower after cross-validation: 96% for healthy volunteers, 77% for IPD and 67% for MSA. In conclusion, using age- and gender-matched healthy volunteer data and anatomical standardisation, it is possible to differentiate between IPD and MSA with high discriminating power in clinically relevant circumstances.     

Myocardial uptake of <Superscript>99m</Superscript>Tc-annexin-V and <Superscript>111</Superscript>In-antimyosin-antibodies after ischemia-reperfusion in rats

Objectives Phosphatidylserin exposure on cell surfaces occurs early during apoptosis and is detected in vivo by using ^99mTc-annexin-V (ANX). Cardiomyocyte membrane disruption is detected in vivo by using ¹¹¹In-antimyosin-antibodies (AM). We aimed to determine if ANX and AM allow evaluation of the time-course of these two distinct cell death events after myocardial ischemia-reperfusion. Methods Coronary tying (20 min) followed by reperfusion (IR) was performed in 31 rats. Twelve of the rats were injected with ANX, 11 with AM, and eight with both tracers. Myocardial uptake of tracers was studied 1–2 h, 4 h, or 24 h after IR by scintigraphy (ANX, n = 14) and autoradiography (all cases), and compared to histology and Apostain staining. Results Scintigraphy was positive in all rats 2 h after IR and in three of five rats at 24 h. On autoradiography, ANX activity was intense in myocardial lesions as early as 1 h post-IR, whereas AM activity was mild at 2 h then increased at 4 h post-IR. ANX and AM uptakes evolved from mid-myocardium to endocardial and epicardial regions from 2 h to 24 h post-IR. Apostain staining was significant in myocardial lesions (p < 10⁶ compared to six sham-operated rats). On histology, myocardial lesion was characterized by interstitial oedema, myocytes necrosis, and dramatic thinning at 24 h. Conclusion These data suggest that ANX and AM allow temporal and regional evaluations of PS exposure and membrane disruption, respectively, during myocytes death after 20-min myocardial ischemia followed by reperfusion. Also, (i) apoptosis starts very early in injured myocardium, (ii) myocyte necrosis occurs later (3–4 h post-reperfusion), and (iii) most dead cells are removed from mid-myocardium between 6 h and 24 h after reperfusion.     

Long-term prognostic value of exercise <Superscript>99m</Superscript>Tc-MIBI SPET myocardial perfusion imaging in patients after percutaneous coronary intervention

The purpose of this study was to evaluate the long-term prognostic value of exercise technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) single-photon emission tomography (SPET) imaging in patients after percutaneous coronary intervention (PCI). Three hundred and eighteen consecutive post-PCI patients who underwent exercise and rest ^99mTc-MIBI SPET myocardial perfusion imaging (MPI) were followed up for 38±27 months. Patients with early revascularisation (<3 months after MPI) were excluded. A semiquantitative visual analysis employing a 20-segment and four-point scoring system was used to define the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS). Death and non-fatal myocardial infarction (MI) were considered as hard events, and late revascularisation procedures (3 months after MPI) as soft events. Fifty-one patients (16.0%) suffered from cardiac events during follow-up, including 1 (0.3%) death, 13 (4.1%) non-fatal MIs, 9 (2.8%) coronary artery bypass grafting procedures and 28 (8.8%) PCIs. According to the SPET results, patients were classified into three groups: patients with normal MPI (SSS=0, n=153), patients with irreversible defects (SDS<3 and SRS>1, n=100) and patients with reversible defects (SDS3, n=65). The annual hard cardiac event rate in patients with reversible defects was 3.9%, which was significantly higher than that in patients with normal MPI (0.2%, ²=7.71; P<0.01). The annual soft cardiac event rate in patients with reversible defects was 10.7%, which was significantly higher than that in patients with irreversible defects (2.5% ²=17.69; P<0.001), and also significantly higher than that in patients with normal MPI (1.5%, ²=33.89; P<0.001). In patients with normal and reversible defects, there was no significant difference in soft and hard cardiac event rates according to whether patients were symptomatic or asymptomatic (P>0.05). However, the annual soft event rate in patients with irreversible defects and symptoms was 5.0%, which was higher than that of 0.6% in asymptomatic patients (²=6.11, P<0.05). Multivariate Cox analysis showed that SSS was the best independent predictor for hard cardiac events (²=12.70; P<0.001) and SDS was the strongest independent predictor for soft cardiac events (²=11.72; P<0.001). Post-PCI patients who have normal exercise ^99mTc-MIBI SPET MPI have a good long-term prognosis, while those with reversible defects are at a higher risk for future cardiac events, without correlation to the chest pain symptoms. However, symptomatic patients with irreversible defects have a higher risk for repeat revascularisation, but not for hard events, compared with asymptomatic patients. Exercise ^99mTc-MIBI SPET MPI has important clinical value for risk stratification and management decision-making in post-PCI patients.     

Reduction of <Superscript>99m</Superscript>Tc-sestamibi and <Superscript>99m</Superscript>Tc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of ^99mTc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, ^99mTc-tetrofosmin (TF), was also examined. Cellular uptake of ^99mTc-MIBI and ^99mTc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N₂ and 5% CO₂ reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.     

Regional cerebral blood flow pattern in normal young and aged volunteers: a99mTc-HMPAO SPET study

The aim of this study was to investigate the normal pattern of regional cerebral blood flow (rCBF) distribution in normal young and aged volunteers using technetium-99m hexamethylpropylene amine oxime (^99m-Te-HMPAO) as a tracer. The region brain perfusion of young and aged subjects was compared, especially regarding rCBF differences due to age and gender, and interhemispheric rCBF asymmetries. Sixty-eight right-handed normal volunteers — 40 young (mean age 29.5±6.3 years) and 28 aged (mean age 71.2±4.3 years) — were included in the study. rCBF was estimated on the basis of a semiquantitative approach by means of a left/right index and two region/reference ratios, using the cerebellum and the whole brain activity as references. A good correlation between these two region/reference ratios was found (P<0.005 in all cerebral regions). The highest rCBF ratios corresponded to the cerebellum, followed by the occipital lobe. The remaining cortical regions (temporal, parietal, frontal and basal ganglia) showed slightly lower values. The white matter showed rCBF ratios substantially lower than the grey matter. In neither young nor aged subjects were significant rCBF differences between the genders found in any of the two region/reference indices employed. Aged subjects showed significantly lower rCBF ratios than young subjects in the left frontal lobe and in the posterior region of the left temporal lobe. In both young and aged subjects, lower perfusion was found in the left hemisphere, except for the white matter region in both age groups and the frontal lobe in the young subjects. Aged subjects presented a slightly higher interhemispheric asymmetry in the frontal lobe. However, interhemispheric asymmetry was minimal (–1.01% to 3.14%). Consequently, a symmetrical rCBF distribution can be assumed between homologous regions, independent of age.     

<Superscript>99m</Superscript>Tc-EDDA/HYNIC-TOC and <Superscript>18</Superscript>F-FDG in thyroid cancer patients with negative <Superscript>131</Superscript>I whole-body scans

Several studies have reported on the expression of somatostatin receptors in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed technetium-99m labelled somatostatin analogue, ^99mTc-EDDA/HYNIC-TOC (^99mTc-TOC), in terms of precise localisation of disease. The study population comprised 54 patients (24 men, 30 women; age range 22–90 years) with histologically confirmed DTC who presented with recurrent or persistent disease as indicated by elevated Tg levels after initial treatment. All patients were negative on the iodine-131 post-therapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) was performed in a subgroup of 36 patients. The study population consisted of two groups: Group A (n=22) comprised patients with disease recurrence as shown by elevated Tg levels but without detectable pathology. In group B (n=32), pre-existing lesions were known. Among the 54 cases, SSTR scintigraphy was true positive in 33 (61.1%), true negative in 4 (7.4%) and false negative in 17 (31.5%) cases, which resulted in a sensitivity of 66%. A total of 138 tumour foci were localised in 33 patients. The fraction of true positive ^99mTc-TOC findings was positively correlated (P<0.01) with elevated Tg levels (higher than 30 ng/ml). Despite two false positive findings, analysis on a lesion basis demonstrated better diagnostic efficacy with ¹⁸F-FDG PET (P<0.001); however, it also revealed substantial agreement between the imaging techniques [Cohens kappa of 0.62 (0.47–0.78)]. In conclusion, scintigraphy with ^99mTc-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localisation diagnostics in thyroid cancer patients with recurrent or metastatic disease.