Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors.
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We have developed a new tumor-avid amino acid, 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), labeled with 18F for nuclear medicine imaging. METHODS: [18F]FACBC was prepared with high specific activity (no carrier added [NCA]) and was evaluated for its potential in tumor localization. A comparative study was performed for [18F]FACBC and [18F]2-fluorodeoxyglucose (FDG) in which the uptake of each agent in 9L gliosarcoma (implanted intracerebrally in Fisher 344 rats) was measured. In addition, the first human PET study of [18F]FACBC was performed on a patient with residual glioblastoma multiforme. Quantitative brain images of the patient were obtained by using a Siemens 921 47-slice PET imaging system. RESULTS: In the rat brain, the initial level of radioactivity accumulation after injection of [18F]FACBC was low (0.11 percentage injected dose per gram [%ID/g]) at 5 min and increased slightly to 0.26 %ID/g at 60 min. The tumor uptake exhibited a maximum at 60 min (1.72 %ID/g), resulting in a tumor-to-brain ratio increase of 5.58 at 5 min to 6.61 at 60 min. In the patient, the uptake of [18F]FACBC in the tumor exhibited a maximum concentration of 146 nCi/mL at 35 min after injection. The uptake of radioactivity in the normal brain tissue was low, 21 nCi/mL at 15 min after injection, and gradually increased to 29 nCi/mL at 60 min after injection. The ratio of tumor to normal tissue was 6 at 20 min after injection. The [18F]FACBC PET scan showed intense uptake in the left frontal region of the brain. CONCLUSION: The amino acid FACBC can be radiofluorinated for clinical use. [18F]FACBC is a potential PET tracer for tumor imaging. (+info)
MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.
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This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates. (+info)
Regional patterns of myocardial sympathetic denervation in dilated cardiomyopathy: an analysis using carbon-11 hydroxyephedrine and positron emission tomography.
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OBJECTIVE: To assess presynaptic function of cardiac autonomic innervation in patients with advanced congestive heart failure using positron emission tomography (PET) and the recently developed radiolabelled catecholamine analogue carbon-11 hydroxyephedrine (HED) as a marker for neuronal catecholamine uptake function. DESIGN AND PATIENTS: 29 patients suffering from dilated cardiomyopathy with moderate to severe heart failure were compared with eight healthy controls. Perfusion scan was followed by HED dynamic PET imaging of cardiac sympathetic innervation. The scintigraphic results were compared with markers of disease severity and the degree of sympathetic dysfunction assessed by means of heart rate variability. RESULTS: In contrast to nearly normal perfusions, mean (SD) HED retention in dilated cardiomyopathy patients was abnormal in 64 (32)% of the left ventricle. Absolute myocardial HED retention was 10.7 (1.0)%/min in controls v 6.2 (1.6)%/min in dilated cardiomyopathy patients (p < 0.001). Moreover, significant regional reduction of HED retention was demonstrated in apical and inferoapical segments. HED retention was significantly correlated with New York Heart Association functional class (r = -0.55, p = 0. 002) and ejection fraction (r = 0.63, p < 0.001), but not, however, with plasma noradrenaline concentrations as well as parameters of heart rate variability. CONCLUSIONS: In this study, using PET in combination with HED in patients with dilated cardiomyopathy, not only global reduction but also regional abnormalities of cardiac sympathetic tracer uptake were demonstrated. The degree of abnormality was positively correlated to markers of severity of heart failure. The pathogenetic mechanisms leading to the regional differences of neuronal damage as well as the prognostic significance of these findings remain to be defined. (+info)
Use of positron emission tomography in evaluation of brachial plexopathy in breast cancer patients.
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18-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has previously been used successfully to image primary and metastatic breast cancer. In this pilot study, 19 breast cancer patients with symptoms/signs referrable to the brachial plexus were evaluated with 18FDG-PET. In 11 cases computerized tomography (CT) scanning was also performed. Of the 19 patients referred for PET study, 14 had abnormal uptake of 18FDG in the region of the symptomatic plexus. Four patients had normal PET studies and one had increased FDG uptake in the chest wall that accounted for her axillary pain. CT scans were performed in 9 of the 14 patients who had positive brachial plexus PET studies; six of these were either normal or showed no clear evidence of recurrent disease, while three CTs demonstrated clear brachial plexus involvement. Of two of the four patients with normal PET studies, one has had complete resolution of symptoms untreated while the other was found to have cervical disc herniation on magnetic resonance imaging (MRI) scan. The remaining two patients almost certainly had radiation-induced plexopathy and had normal CT, MRI and PET study. These data suggest that 18FDG-PET scanning is a useful tool in evaluation of patients with suspected metastatic plexopathy, particularly if other imaging studies are normal. It may also be useful in distinguishing between radiation-induced and metastatic plexopathy. (+info)
Sperm transport in the human female genital tract and its modulation by oxytocin as assessed by hysterosalpingoscintigraphy, hysterotonography, electrohysterography and Doppler sonography.
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The transport function of the uterus and oviducts and its modulation by oxytocin has been examined using hysterosalpingoscintigraphy, recording of intrauterine pressure, electrohysterography and Doppler sonography of the Fallopian tubes. After application to the posterior vaginal fornix, a rapid (within minutes) uptake of the labelled particles into the uterus was observed during the follicular and during the luteal phase of the cycle in all patients. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Transport was directed predominantly into the tube ipsilateral to the ovary bearing the dominant follicle; the contralateral oviduct appeared to be functionally closed. The proportion of patients exhibiting ipsilateral transport did increase concomitant with the increase of the diameter of the dominant follicle. That ipsilateral transport has biological significance is suggested by the observation that the pregnancy rate following spontaneous intercourse or insemination was significantly higher in those women in whom ipsilateral transport could be demonstrated than in those who failed to exhibit lateralization. Oxytocin administration was followed by a dramatic increase in the amount of material transported to the ipsilateral tube, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. Continuous recording of intrauterine pressure before and after oxytocin administration did show an increase in basal tonus and amplitude of contractions and a reversal of the pressure gradient from a fundo-cervical to a cervico-fundal direction. These actions of oxytocin were accompanied by an increase in amplitude of potentials recorded by electrohysterography. These data support the view that uterus and Fallopian tubes represent a functional unit that is acting as a peristaltic pump and that the increasing activity of this pump during the follicular phase of the menstrual cycle is reflected by an increased transport into the oviduct ipsilateral to the ovary bearing the dominant follicle. In addition, they strongly suggest a critical role of oxytocin in this process. Failure of this mechanism appears to be a cause of subfertility or infertility, as indicated by the low pregnancy rate following intrauterine insemination or normal intercourse in the presence of patent Fallopian tubes. It may be regarded as a new nosological entity for which we propose the term tubal transport disorder (TTD). Since pregnancy rate of such patients is normal when treated with in-vitro fertilization (IVF), hysterosalpingoscintigraphy seems to be useful for the choice of treatment modalities in patients with patent Fallopian tubes suffering from infertility. (+info)
Measurement of striatal D2 dopamine receptor density and affinity with [11C]-raclopride in vivo: a test-retest analysis.
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Subacute and long-term stability of measurements of D2 dopamine receptor density (Bmax), affinity (Kd) was studied with positron emission tomography in eight healthy male volunteers. [11C]-Raclopride and the transient equilibrium method were used to measure D2 receptor characteristics. The interval between measurements (scan pairs) was 3 to 7 weeks (subacute) for four subjects and 6 to 11 months (long-term) for four subjects. A test-retest analysis of quantitative measurements of D2 receptor Bmax and Kd was compared with that done on binding potential (BP, Bmax/Kd) measures. In addition, the effect of error in defining the transient equilibrium time (tmax) in the parameter estimation procedure was explored with simulations. The subacute test-retest indicates good reproducibility of D2 receptor density, affinity, and BP ratio measurements with intraclass correlation coefficients of 0.90, 0.96, and 0.86, respectively. The variability of the measurements after 6 to 11 months was slightly higher than that seen in a subacute testing for Kd and more clearly so for binding potential and Bmax. The absolute variability in Bmax (14.5%) measurements was consistently higher than that of Kd (8.4%) or BP (7.9%) both in subacute and long-term measurements. Simulations indicated that the Bmax and Kd estimation procedure is more sensitive to error in the tmax than that for the BP. The results indicate a good overall stability of the equilibrium method with [11C]raclopride for measuring dopamine D2 receptor binding characteristics in the striatum. The BP approach is more stable than Kd and especially Bmax measurements. Error in defining the tmax in particular in the low specific radioactivity scan may be one source of greater variability in Bmax versus BP. However, a higher intraindividual variability in measurements of the D2 receptor Bmax also may include a component of continuous regulation of this parameter over time. These methodologic aspects should be considered in the design and interpretation of longitudinal studies on D2 dopamine receptor characteristics with [11C]-raclopride. (+info)
Loss of D2 receptor binding with age in rhesus monkeys: importance of correction for differences in striatal size.
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The relation between striatal dopamine D2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with 11C-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain. (+info)
Human complex sound analysis.
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The analysis of complex sound features is important for the perception of environmental sounds, speech and music, and may be abnormal in disorders such as specific language impairment in children, and in common adult lesions including stroke and multiple sclerosis. This work addresses the problem of how the human auditory system detects features in complex sound, and uses those features to perceive the auditory world. The work has been carried out using two independent means of testing the same hypotheses; detailed psychophysical studies of neurological patients with central lesions, and functional imaging using positron emission tomography and functional magnetic resonance imaging of normal subjects. The psychophysical and imaging studies have both examined which brain areas are concerned with the analysis of auditory space, and which are concerned with the analysis of timing information in the auditory system. This differs from many previous human auditory studies, which have concentrated on the analysis of sound frequency. The combined lesion and functional imaging approach has demonstrated analysis of the spatial property of sound movement within the right parietal lobe. The timing work has confirmed that the primary auditory cortex is active as a function of the time structure of sound, and therefore not only concerned with frequency representation of sounds. (+info)