Evaluation of a new leukocyte labeling procedure with 99mTc-HMPAO

A technique for labeling leukocytes with 99mTc using hexamethylpropylene-amineoxime (HMPAO) was evaluated in vitro. The labeling procedure resulted in a cell bound fraction of radioactivity of 56% after 99mTc incubation and 96% after 1 washing of cells. In the final cell suspension 84% of the radioactivity was attached to the polymorphonuclear (PMN) leukocytes constituting 94% of white cells. Only 5% was bound to residual red blood cells. The stability evaluated in autologous plasma showed a decline of cell bound activity from 96% to 84% over 3 h. The chemotactic function of PMN leukocytes was unaffected by the labeling procedure. These findings demonstrate that HMPAO, albeit cell unspecific, is efficient for labeling PMN leukocytes with 99mTc. The stability of the labeling procedure is high and the technique does not affect cell function. No other current 99mTc leukocyte labeling technique possesses all these qualities.     

Evaluation of a new leukocyte labeling procedure with 99mTc-HMPAO

A technique for labeling leukocytes with ^99mTc using hexamethylpropylene-amineoxime (HMPAO) was evaluated in vitro. The labeling procedure resulted in a cell bound fraction of radioactivity of 56% after ^99mTc incubation and 96% after 1 washing of cells. In the final cell suspension 84% of the radioactivity was attached to the polymorphonuclear (PMN) leukocytes constituting 94% of white cells. Only 5% was bound to residual red blood cells. The stability evaluated in autologous plasma showed a decline of cell bound activity from 96% to 84% over 3 h. The chemotactic function of PMN leukocytes was unaffected by the labeling procedure. These findings demonstrate that HMPAO, albeit cell unspecific, is efficient for labeling PMN leukocytes with ^99mTc. The stability of the labeling procedure is high and the technique does not affect cell function. No other current ^99mTc leukocyte labeling technique possesses all these qualities.     

Hard metal pneumoconiosis: another cause of diffuse interstitial fibrosis

Three patients developed diffuse pulmonary fibrosis caused by exposure to aerosolized cobalt while working in the tungsten carbide tool industry. Two cases were severe and one of these has died of cor pulmonale. The third is mildly disabled. The pathophysiology is reviewed. Clinicians and radiologists should be aware of hard metal exposure as a cause of diffuse interstitial fibrosis.     

Quantitative analysis of 99mTc-HMPAO kinetics in epilepsy

A convection-diffusion model is applied for the determination of cerebral circulation parameters in patients with frontal lobe epilepsy. The method employs 99mTc-HMPAO, dynamic brain imaging and SPECT. The model takes into account both the capillary and cell permeabilities of HMPAO. Experiments were performed in 41 patients with epilepsy and 10 patients without evident cerebrovascular disease. The results indicate that in the inter ictal epileptic foci, cerebral blood flow was reduced (18% +/- 19%), cerebral blood volume was increased (21% +/- 14%), and the capillary permeability of HMPAO in the affected side was on the average 50% of the value in the contralateral side, whereas the reflux from brain tissue to blood was increased. These findings mean that HMPAO diffusion across the blood brain barrier is restricted and HMPAO slackly interacts with the intra cellular component of the inter ictal epileptic foci.     

Evaluation of alveolo-capillary permeability in thyrotoxicosis using Tc-99m DTPA aerosol scintigraphy

Surfactant secreted from type II pneumocytes plays an important role in alveolo-capillary permeability. In thyrotoxicosis, high levels of T3 receptors detected at these cells might affect the alveolo-capillary permeability due to increased serum thyroid hormone levels. The results by CO-diffusion capacity measurement in thyrotoxicosis are conflicting. Changes in alveolo-capillary membrane permeability resulting from thyrotoxicosis are not well established yet. This prompted us to investigate the alveolo-capillary permeability in thyrotoxic patients in comparison with CO-diffusing capacity. For this aim twenty-two non-smoking thyrotoxic patients (before treatment) and fifteen healthy voluntary controls underwent 99mTc-DTPA aerosol scintigraphy. CO-diffusing and pulmonary function tests were performed in all subjects. After ventilation of radiotracer through a nebulizer for 15 minutes, 30 dynamic images (1 frame/minute) were taken from both lungs. ROI's were drawn over both lung areas, and the time-activity curves were generated. Then clearance half time (CT1/2) for radioaerosol was obtained. CT1/2 of thyrotoxic patients did not differ from that of the controls: 77.9 +/- 25.9 min vs. 79.4 +/- 22.3 min; p > 0.05. Similar result was found for CO-diffusion parameters. Also there was no significant correlation between CT1/2 and CO-diffusion parameters. We concluded that in patients with thyrotoxicosis, the alveolo-capillary permeability is unaffected. Further experimental research is needed to establish the possible effects of thyroid hormones on alveolo-capillary membrane.     

Brain perfusion SPECT imaging before and during the acetazolamide test using 99mTc-HMPAO

A new method using brain perfusion 99mTc-HMPAO SPECT imaging was developed for evaluating cerebral perfusion reserve by the acetazolamide test with a short period. The first SPECT study was carried out for 13.5 min to obtain SPECT images at the resting state after 3 min postinjection of 555 MBq (15 mCi) of 99mTc-HMPAO. At the same time as the start of the first SPECT study, 1 g of acetazolamide was intravenously injected. Immediately after the stop of the 1st SPECT study, 925 MBq (25 mCi) of 99mTc-HMPAO from the same vial as in the first study was additionally injected. Three minutes later the second SPECT study was carried out for 10 min. After reconstruction the tomographic images in the first study were subtracted from the images in the second study to obtain those during the acetazolamide test after correction of the time differences in data acquisition between the two studies. This subtraction technique gives independent brain perfusion SPECT images before and during the acetazolamide test. Besides, the regional flow changes during the test were quantitatively analyzed. In conclusion this method seems to be practically useful for evaluating regional brain perfusion before and during drug treatments as a consecutive study with a short period of approximately 30 min.     

Quantitative analysis of99mTc-HMPAO kinetics in epilepsy

A convection-diffusion model is applied for the determination of cerebral circulation parameters in patients with frontal lobe epilepsy. The method employs^99mTc-HMPAO, dynamic brain imaging and SPECT. The model takes into account both the capillary and cell permeabilities of HMPAO. Experiments were performed in 41 patients with epilepsy and 10 patients with out evident cerebrovascular disease. The results indicate that in the inter ictal epileptic foci, cerebral blood flow was reduced (18%±19%), cerebral blood volume was increased (21%±14%), and the capillary permeability of HMPAO in the affected side was on the average 50% of the value in the contralateral side, whereas the reflux from brain tissue to blood was increased. These findings mean that HMPAO diffusion across the blood brain barrier is restricted and HMPAO slackly interacts with the intra cellular component of the inter ictal epileptic foci.     

The assessment of 99mTc-HMPAO tumor scintigraphy using VX-2 tumors in rabbits]

Tumor scintigraphy using 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) was performed in VX-2 tumors implanted in the muscles of the lower limbs of rabbits to evaluate the possibility that this agent could be used to estimate the blood perfusion of the tumor. The distribution of 99mTc-HMPAO in the tumor immediately after the intravenous injection of this radiopharmaceutical exhibited almost the same distribution on the static image 1 hour after administration. Tumor time-activity curve for 99mTc-HMPAO revealed initial peak after the injection followed by fading of 99mTc-HMPAO activity and subsequent gradual decrease in activity over the next 1 hour. The ratio of 99mTc-HMPAO activity in the tumor to that in normal muscle tissue during this next 1 hour was high and independent of time. These findings indicate that static 99mTc-HMPAO scintigraphy can provide qualitative but not quantitative data useful in the estimation of tumor blood perfusion. Moreover, comparison of distribution of 99mTc-HMPAO on the static images and angiographic, histological findings also suggest that static 99mTc-HMPAO images accurately reflect tumor blood perfusion.     

Guidelines for the labelling of leucocytes with 99mTc-HMPAO

We describe here a protocol for labelling autologous white blood cells with ^99mTc-HMPAO based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations.     

Comparison of quantitative 99mTc-HMPAO and 67Ga citrate lung scans in patients with active diffuse infiltrative lung disease

Diffuse infiltrative lung disease (ILD) is a heterogeneous group of disorders that predominantly affect the lung parenchyma and spare the airway. To objectively assess the degree of pulmonary vascular endothelium damage in active ILD, lung/liver uptake ratios (L/L ratios) on 99mTc hexamethylpropylene amine oxime (99mTc-HMPAO) lung scans were determined in 21 patients with active ILD. Meanwhile, the 67Ga citrate uptake index (GUI) on 67Ga lung scans was measured in order to evaluate the severity of lung inflammation in active ILD. The results show there were statistically significant differences between normal controls and patients with active ILD, as shown in the L/L ratio and GUI. However, when the patients were divided into two groups: (1) eight patients with normal chest X-ray findings, and (2) 13 patients with abnormal X-ray findings, there was no significant difference between groups 1 and 2 for the results of L/L ratio and GUI. In addition, no correlation between the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation was found. In conclusion, L/L ratios on 99mTc-HMPAO lung scans and GUI on 67Ga lung scans are different to the findings of chest X-rays and have the potential to objectively detect the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation in active IDL. However, the relationship between L/L ratio and GUI in active ILD is not significant.     

Localization and diagnosis of septic endoprosthesis infection by using 99mTc-HMPAO labelled leucocytes

The aim of this study was to evaluate, retrospectively, the diagnostic value of Tc hexamethylpropylene amine oxime (99mTc-HMPAO) labelled autologous leucocytes for the preferred septic localizations of the infection of the endoprosthesis. We retrospectively reviewed 67 patients with implanted endoprostheses. Diagnosis was found in 42/67 patients. In 25/67 patients we were able to negate an acute pathological process of infection of the endoprosthesis. Our patients were divided into three groups according to the type of endoprosthesis (hip joint, knee joint, shoulder joint). The localizations of the endoprosthesis disorders are shown. The preferred localizations of the acute infection of the hip endoprosthesis are the regio intertrochanterica and the middle part of the shaft of the prosthesis. The preferred localization of the acute infection of the knee endoprosthesis is the proximal shaft of the tibia. The preferred localization of the acute infection of the shoulder endoprosthesis is the distal end of the prosthesis in the proximal humerus. It is hoped that the knowledge of these preferred localizations of infection of endoprosthesis will help patients and doctors in diagnosis and treatment in the future.     

Evaluation of regional cerebral blood flow with 99mTc-HMPAO in primary antiphospholipid antibody syndrome.

In this study, 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT was used to evaluate the regional cerebral blood flow (rCBF) of the brain in patients with primary antiphospholipid antibody syndrome (PAPS). METHODS: Twenty-two women who were PAPS patients, aged 28-60 y, with mild neuropsychiatric manifestations and normal brain MRI findings were enrolled in this study. Brain HMPAO SPECT was performed to detect brain abnormalities. Meanwhile, serum anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) were measured. RESULTS: HMPAO SPECT revealed hypoperfusion lesions in 16 of 22 (73%) PAPS patients. Cerebral cortex and cerebellum were the most and the least commonly involved areas, respectively. Eighteen of 22 (82%) and 14 of 22 (64%) patients had positive ACA and positive LA, respectively. ACA and LA results were related to HMPAO SPECT findings. CONCLUSION: HMPAO SPECT is a sensitive tool for detecting brain abnormalities in PAPS patients with only mild neuropsychiatric manifestations and normal brain MRI findings.     

The behavior of 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain

99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how 99mTc-HMPAO changed in the blood and brain. The 99mTc-HMPAO, which was prepared by adding of 99mTcO4- to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed 99mTc, and 99mTc-pertechnetate. The percentage of the primary complex in 99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When 99mTc-HMPAO was injected into patients, 99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma, 99mTc was found to be associated with proteins such as albumin and globulin. 99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of 99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific 99mTc binding protein was present in the brain. Considering the instability of 99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing 99mTc-HMPAO to pass through the BBB and to be fixed in the brain.     

The behavior of99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain

^99mTc-hexamethylpropyleneamineoxime (^99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how^99mTc-HMPAO changed in the blood and brain. The^99mTc-HMPAO, which was prepared by adding of^99mTcO _- ⁴ to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed^99mTc, and^99mTc0pertechnetate. The percentage of the primary complex in^99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When^99mTc-HMPAO was injected into patients,^99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma,^99mTc was found to be associated with proteins such as albumin and globulin.^99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of^99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific^99mTc binding protein was present in the brain. Considering the instability of^99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing^99mTc-HMPAO to pass through the BBB and to be fixed in the brain.     

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy

Aim  

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy.     

Clinical assessment of 99mTc-HMPAO scintigraphy in thoracic tumors]

99mTc-hexamethylpropylene amineoxime (99mTc-HMPAO) scintigraphy was performed in 15 malignant tumors in 11 patients and a patient with bronchopneumonia. A high 99mTc-HMPAO affinity for the tumors was observed on SPECT, however, the mean tumor/contralateral normal lung ratios of 99mTc-HMPAO activity (1.26) was lower than that of 201Tl-chloride (2.29). 99mTc-HMPAO uptake was seen not only in the tumors but also in the bronchopneumonia, atelectasis, and irradiated lung (containing radiation fibrosis). Moreover, a diffuse uptake in the lung was seen in a patient received repeated chemotherapy. Therefore, it is emphasized that there is a non-specific 99mTc-HMPAO uptake in those various pulmonary conditions.     

99mTc-HMPAO brain SPECT in a case of HSV encephalitis

We present a case of encephalitis caused by Herpes Simplex Virus in a 57 year old woman. The acute picture was suggestive of viral infection without associated neurological symptoms. Due to the posterior appearance of neurological focality, cerebral spinal fluid (CSF) was analyzed. It showed pleocytosis and lymphocytosis, inflammatory process data, and serological test with positivity for Simple Herpes Virus (SHV) subtypes I and II. During admission, other complementary tests were performed: EEG, CT, MRI, cerebral perfusion SPECT; the later supplied significant data regarding anatomical neuroimaging (CT, MRI) in regards to bihemispheral extension of the encephalic condition. Furthermore, after clinical discharge, persistent metabolic abnormality was demonstrated in temporal cortex, responsible for concomitant mixed aphasia.