Uptake of SPECT radiopharmaceuticals in neocortical brain cultures

The uptake, retention and uptake antagonism of ²⁰¹Tl-DDC, ²⁰¹Tl-Cl, ¹²³I-IMP, ^99mTc-HMPAO and ^99mTc-O ₄ ^– were compared in rat neocortex cultures. ²⁰¹Tl-DDC and ¹²³I-IMP revealed the highest uptake of radioactivity in the cultures. ⁹⁹mTc-HMPAO and ¹²³I-IMP showed the highest retention of radioactivity within the tissue in washout experiments. Blocking of bioelectric activity by tetrodotoxin did not significantly affect the uptake of the radiopharmaceuticals (RPHA). Inhibition of Na-K-ATPase by ouabain inhibited the uptake of ²⁰¹Tl-Cl (77%) and ²⁰¹Tl-DDC (27%). Imipramine showed a significantly stronger inhibitory effect on ¹²³I-IMP uptake in comparison with the effect on other RPHA. ^99mTc-O ₄ ^– was not concentrated within the cultured tissue. Under the in vitro conditions used in this study, the various RPHA were characterised by distinct differences in their interaction with cortical brain tissue.     

EANM procedure guideline for brain perfusion SPECT using 99mTc-labelled radiopharmaceuticals, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of brain perfusion single photon emission computed tomography (SPECT) studies using ^99mTc-labelled radiopharmaceuticals. The aim is to achieve a high quality standard for brain perfusion SPECT imaging, which will increase the diagnostic impact of this technique in clinical practice. The present document replaces a former version of the guideline published in 2001 which was inspired by the Society of Nuclear Medicine Procedure Guideline for Brain Perfusion SPECT [1], the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.     

A simulation of dynamic SPECT using radiopharmaceuticals with rapid clearance.

Data acquisition in SPECT assumes that there is no change in radionuclide distribution during data collection. However, this assumption is not valid in radiopharmaceuticals with rapid temporal changes in radioactivity. Artifacts and quantitative errors are studied using phantom studies, mathematical models, and clinical myocardial data. Projection data of each model were sequentially multiplied by weighting coefficients that varied mono-exponentially with time, and the SPECT images were reconstructed. A long data acquisition time in comparison to the clearance of the tracer can be a significant cause of artifact. When the myocardial septum-to-lateral count ratio is used as an index of distortion, a shorter acquisition time than the effective half-life of the tracer is required to reduce the error of the septum-to-lateral count ratio to within 10%. Since 180 degrees rotation acquisition causes artifacts depending on the direction of rotation, 360 degrees acquisition is preferable. Continuous repetitive rotation acquisition is a suitable method for dynamic SPECT to reduce quantitative errors and artifacts.     

Positron emission tomography radiopharmaceuticals for imaging brain Beta-amyloid

Alzheimer's disease (AD) is defined histologically by the presence of extracellular β-amyloid (Aβ) plaques and intraneuronal neurofibrillary tangles in the cerebral cortex. The diagnosis of dementia, along with the prediction of who will develop dementia, has been assisted by magnetic resonance imaging and positron emission tomography (PET) by using [(18)F]fluorodeoxyglucose (FDG). These techniques, however, are not specific for AD. Based on the chemistry of histologic staining dyes, several Aβ-specific positron-emitting radiotracers have been developed to image neuropathology of AD. Among these, [(11)C]PiB is the most studied Aβ-binding PET radiopharmaceutical in the world. The histologic and biochemical specificity of PiB binding across different regions of the AD brain was demonstrated by showing a direct correlation between Aβ-containing amyloid plaques and in vivo [(11)C]PiB retention measured by PET imaging. Because (11)C is not ideal for commercialization, several (18)F-labeled tracers have been developed. At this time, [(18)F]3'-F-PiB (Flutemetamol), (18)F-AV-45 (Florbetapir), and (18)F-AV-1 (Florbetaben) are undergoing extensive phase II and III clinical trials. This article provides a brief review of the amyloid biology and chemistry of Aβ-specific (11)C and (18)F-PET radiopharmaceuticals. Clinical trials have clearly documented that PET radiopharmaceuticals capable of assessing Aβ content in vivo in the brains of AD subjects and subjects with mild cognitive impairment will be important as diagnostic agents to detect in vivo amyloid brain pathology. In addition, PET amyloid imaging will also help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of antiamyloid therapeutics currently under development in clinical trials.     

轻度脑外伤患者SPECT局部脑血流显像

目的 探讨SPECT脑血流灌注显像在研究轻度脑外伤后临床症状发病机理中的作用。方法对39例无意识丧失、CT检查正常的轻度脑外伤患者进行^99Tc^m-双半胱乙酯(ECD)脑血流灌注断层显像。以双侧小脑平均每像素的均数为参比值，计算各大脑感兴趣区(ROI)放射性计数比值(RAR)。大脑皮质或基底神经节RAR低于70％，颞叶中部低于50％视为异常。结果39例患者中23例(59％)SPECT显示异常，其中3例为弥漫性血流灌注减低，20例为局部血流灌注减低灶，共计74个病灶。伤后3个月内脑血流灌注异常15例，2例为弥漫性血流灌注减低，13例为局灶性血流灌注减低；13例中发现病灶58个。8例受伤3个月后显像异常者，1例为弥漫性血流灌注减低，7例为局灶性血流灌注减低，发现病灶16个。结论 轻度脑外伤后患者主要症状为头痛、头昏、记忆力减退；无意识丧失的脑外伤患者可出现局部脑血流灌注减低，且SPECT检查比CT灵敏。     

99mTc HM-PAO brain perfusion SPECT in brain death

Diagnosis of brain death must be certain to allow discontinuation of artificial ventilation and organ transplantation. Brain death is present when all functions of the brain stem have irreversibly ceased. Clinical and electrophysiological criteria may be misinterpreted due to drug intoxication, hypothermia or technical artefacts. Thus, if clinical assessment is suboptimal, reliable early confirmatory tests may be required for demonstrating absence of intracranial blood flow. We have easily carried out and interpreted^99mTc HM-PAO SPECT in a consecutive series of 40 comatose patients with brain damage, without discontinuing therapy. Brain death was diagnosed in 7 patients, by recognising absence of brain perfusion, as shown by no intracranial radionuclide uptake. In patients in whom perfusion was seen on brain scans, HM-PAO SPECT improved assessment of the extent of injury, which in general was larger than suggested by CT.     

Ictal SPECT in neocortical epilepsies: clinical usefulness and factors affecting the pattern of hyperperfusion

Introduction: The aims of this analysis were to: (1) determine the value of ictal SPECT in the localization of neocortical epileptogenic foci, (2) evaluate the relationships between the results of ictal SPECT and other potential affecting factors, and (3) compare traditional visual analysis and the subtraction method.Methods: We retrospectively analyzed 81 consecutive patients with neocortical epilepsy who underwent epilepsy surgery and achieved a favourable surgical outcome, including 36 patients with normal MRI. Side-by-side visual analysis and subtraction images were classified as correctly localizing,correctly lateralizing, or non-localizing/non-lateralizing images according to the resected lobe.Results: Side-by-side visual analysis and subtraction SPECT correctly localized the epileptogenic lobe in 58.9% and 63.0% of patients, respectively. The two methods were complementary and the diagnostic sensitivity of ictal SPECT using the two methods was 79.0%. Ictal SPECT using the visual method correctly localized the epileptogenic lobe more frequently in patients with a localizing pattern of ictal scalp EEG at the time of radioligand injection. When using subtraction images, an injection delay of less than 20 s after seizure onset was significantly correlated with correct localization. The subtraction method was superior to the visual method for localizing frontal lobe epilepsy (FLE) and parietal lobe epilepsy (PLE), and in patients with non-localizing/non-lateralizing EEG at onset.Conclusions: Ictal SPECT analyses using visual and subtraction methods are useful and complementary for the localization of the epileptogenic foci of neocortical epilepsy. Early radioligand injection and ictal EEG patterns are related to ictal SPECT localization. The subtraction method may be more useful in some epileptic syndromes.     

Interventional brain SPECT—A review

Brain SPECT with HMPAO or ECD has—due to its short accumulation period—a rather high time resolution of approx. 60 sec. Compared to isopropyl amphetamine (I-123) and FDG-PET, shortlasting interventions may be evaluated by SPECT. Usually, a two-step approach is used, injecting one third of the dose under baseline conditions and two thirds during intervention. The first study is then subtracted from the second study, resulting in a “difference” image which allows to calculate the effect of the intervention. These interventional procedures may include drug, mechanical, and mental intervention as well as ictal, blood pressure and receptor intervention. Moreover, the difference of pCO₂ after hyperventilation or hypoventilation may also be used as a stimulus. The above mentioned procedures are described in detail.     

Uptake of 11C-l-and d-methionine in brain tumors

¹¹C-labeled l-and d-methionine uptake was measured in seven patients with brain tumors using positron emission tomography. Tumors accumulated both isomers of the tracer. The strongest uptake occurred in tumors with a high grade of malignancy, while low grade tumors accumulated less activity. The l to d uptake ratio in tumor regions ranged from 0.92–1.25. Conventional ^99mTc-DTPA scans revealed blood-brain barrier damage in two patients with no or only slight ¹¹C-methionine accumulation, while one patient with a negative ^99mTc-DTPA scan accumulated ¹¹C-methionine in the tumor region. In view of the biochemical pathway of methionine and the present findings, it is concluded that the uptake reflects metabolic activity in brain tissue rather than uptake by diffusion due to disruption of the blood-brain barrier.     

Compartment analysis of 123I-IMP brain SPECT

To clarify the kinetics of N-isopropyl [123I]p-iodoamphetamine (IMP) in the brain, 2-compartment analysis was applied for brain SPECT with 57-minute dynamic scan in 9 subjects. The model consisted of blood component and brain tissue component. Two transfer rate constants were defined; k1 showed the rate from the blood to the brain tissue, and k2 was that of back diffusion. The late scan was performed 210 minutes after the tracer injection. Suitable k values best fitting to the dynamic data were determined for all regions of interest. Predicted regional cerebral activity at 210 minutes using 57-minute dynamic data was well agreed with measured activity. These showed the kinetics of IMP in the brain was well described by the 2-compartment model. The partition coefficient (k1/k2 ratio) was as large as about 35, and almost constant in the various brain structures including hypoperfused areas. These findings indicated that the initial IMP images reflected the reasonable CBF distribution, which gave relatively reliable CBF values even if using microsphere model.     

Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals

The brain extraction of fifteen C-11-labeled compounds during a single capillary transit was studied in adult baboons by external detection of these tracers after injection into the internal carotid artery. The log Poct (partition coefficient for octanol/water) values of these compounds range from --0.7 to greater than 4.0. A parabolic relationship was found between the log Poct value of the C-11-labeled compounds and the fraction of the radiopharmaceutical entering the brain. Compounds with log Poct values between 0.9 and 2.5 were found to pass freely across the blood-brain barrier at a cerebral blood flow of 100 ml X min-1 X hg-1. An apparently decreased extraction of very lipophilic compounds was shown to be related to binding of the tracer to blood components and macromolecules (red blood cells, albumin, etc.). These data suggest that a radiopharmaceutical designed to measure blood flow should have a log Poct value of between 0.9 and 2.5.     

Clinical correlate of brain SPECT perfusion abnormalities in fibromyalgia

The purpose of this study was to investigate the specific clinical correlate of brain SPECT perfusion abnormalities reported in fibromyalgia. METHODS: We performed a whole-brain voxel-based correlation analysis involving regional cerebral blood flow and various parameters related to pain (Visual Analog Scale, Tubingen Pain Behavior Scale, and Questionnaire Douleur de Saint-Antoine Scale), disability (Fibromyalgia Impact Questionnaire [FIQ]), and anxiety and depression status (Hospital Anxiety and Depression scale) in 20 patients with fibromyalgia (P voxel < 0.005). Ten healthy control women were also included, in order to determine areas of significant hypo- and hyperperfusions in patients. RESULTS: FIQ total score was positively correlated with bilateral parietal perfusion, including postcentral cortex. These clusters of correlation were included in the areas of significant hyperperfusion. FIQ total score was also negatively correlated with perfusion of a left anterior temporal cluster, included in the areas of significant hypoperfusions. No other clinical correlation was observed with regional cerebral blood flow. CONCLUSION: These results show that brain perfusion abnormalities in patients with fibromyalgia are correlated with the clinical severity of the disease.