Clinical application and quantitative evaluation of generator-produced copper-62-PTSM as a brain perfusion tracer for PET (original) (raw)
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Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1996
The purpose of this study was to determine the suitability of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) for estimating myocardial blood flow (MBF) over a wide range of flow by comparison with 13N-ammonia (13NH3). PET studies using 62Cu-PTSM and 13NH3 were performed at rest and after pharmacological vasodilatation in 9 normal subjects and 13 patients with coronary artery disease (CAD). According to the microsphere method, values for the product of the extraction fraction and MBF (ExMBF) were calculated using both tracers. In static images, the percent uptake (normalized to the peak count) of each tracer was measured in patients with CAD. The myocardial tracer distribution in the normal subjects was significantly higher in the inferior wall in the 62Cu-PTSM studies and lower in the lateral wall in the 13NH3 studies. The ExMBF values showed linear correlation for both tracers in a low flow range. In a high flow range, however, the ExMBF values for 62Cu-PTSM were no...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2001
To evaluate the appropriate model for calculating regional cerebral blood flow (rCBF) with PET and H(2)(15)O, the values obtained from 1- and 2-compartment analyses were compared. Dynamic PET scans were performed on 12 healthy volunteers after injection of H(2)(15)O in 2 conditions of baseline and visual stimulation. Calculation of rCBF was performed using the 2-weighted integral (WI) and autoradiographic methods for the 1-compartment analysis, and the 3-WI method was followed for the 2-compartment analysis. Arterial blood radioactivity was counted continuously and corrected for delay and dispersion. The rCBF images were transformed into the Talairach space and analyzed by statistical parametric mapping to identify regional differences in the 2 methods. The values obtained from regions of interest also were compared. Although the difference in global CBF between the 2 models was not significant, rCBF values in the large arteries and neighbor areas were significantly greater in the 2...
Journal of Cerebral Blood Flow & Metabolism, 1988
The tracer appearance time relative to the ra dial artery-sampling site has been evaluated in six brain locations in five human subjects using dynamic positron emission tomography (PET) following the bolus injection of H2150. There was a maximum difference of ± 2 s from the average in each location. To globally adjust the timing difference between the measured arterial curve and the 150-labeled water is one of the most commonly used tracers for the measurement of CBF by posi tron emission tomography (PET) (Herscovitch et aI., 1983; Raichle et aI., 1983). With this method, it is necessary to measure the arterial input function in addition to the radioactivity distribution in the brain. As described in our previous report (lid a et aI., 1986), great attention has to be paid to the mea surement of the arterial input function in the auto radiographic CBF method using the bolus injection of H 2 150. Our previous article emphasized mainly the importance of dispersion effects in the measure ment of the arterial concentration curve. Another important error source is related to the correct as sessment of the time delay between the peripher ally sampled input function and the brain tissue ra dioactivity measurement. Since the blood radioac tivity concentration is commonly sampled from the
Human biodistribution and dosimetry of the PET perfusion agent copper-62-PTSM
Journal of Nuclear Medicine
Copper-62-pyruvaldehyde bis(N4-methyl)thiosemicarbazone (PTSM) has been proposed as a generator-produced radiopharmaceutical for perfusion imaging using PET. Several clinical studies have demonstrated the ability of 62Cu-PTSM to quantitate myocardial and cerebral perfusion in humans. Because 62Cu-PTSM is genera tor-produced, it can be provided to clinical centers without cyclotron availability and, therefore, represents a cost-effective, practical PET perfusion tracer for clinical applications. To assess the safety, time-dependent biodistribution, and whole-body and organ-specific absorbed radiation dose estimates of this tracer, a Phase I study of 6ZCu-PTSM was performed using whole-body imaging with PET in 10 healthy volunteers and with the radiopharmaceutical delivered by a compact modular generator unit. Methods: Five male and five female subjects underwent a series of clinical tests and head-tomidthigh, whole-body PET scans at three time points over 1 hr after intravenous injection of 62Cu-PTSM. Before injection of the tracer, PET transmission scans were performed and used to correct the emission data for attenuation. Final image data were expressed in units of mCi/cc. Using standard organ weights, the percent injected dose per organ was calculated. Biodistribution data were obtained at three different time points and from these data biological half-lives in different organs were determined for calculation of radiation absorbed dose estimates. Results: The liver was seen as the critical organ receiving a dose of 0.0886 rad/mCi. This organ defined the maximum single injected dose at 56 mCi using the limit of 5 rads to a critical organ per study per year. The whole-body dose is 0.0111 rad/mCi, resulting in a 0.622 rad exposure with a maximum single injection dose. Only trace levels of activity were found in the urine, which suggests low levels of urinary excretion and bladder expo sure. No significant clinical, electrocardiographic or laboratory ab normalities were seen after the injection of 62Cu-PTSM. Conclu sion: Copper-62-PTSM is a clinicallysafe radiopharmaceuticalwith favorable dosimetry for human studies at injected doses significantly above those projected for use in clinical studies.
Semi-quantitative cerebral blood flow parameters derived from non-invasive [15O]H2O PET studies
Journal of Cerebral Blood Flow & Metabolism
Quantification of regional cerebral blood flow (CBF) using [15O]H2O positron emission tomography (PET) requires the use of an arterial input function. Arterial sampling, however, is not always possible, for example in ill-conditioned or paediatric patients. Therefore, it is of interest to explore the use of non-invasive methods for the quantification of CBF. For validation of non-invasive methods, test–retest normal and hypercapnia data from 15 healthy volunteers were used. For each subject, the data consisted of up to five dynamic [15O]H2O brain PET studies of 10 min and including arterial sampling. A measure of CBF was estimated using several non-invasive methods earlier reported in literature. In addition, various parameters were derived from the time-activity curve (TAC). Performance of these methods was assessed by comparison with full kinetic analysis using correlation and agreement analysis. The analysis was repeated with normalization to the whole brain grey matter value, pr...
Research Square (Research Square), 2022
Background: Dopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBF R) can be measured with the DAT-specific positron emission tomography (PET) tracer [ 18 F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [ 15 O]H 2 O PET (H 2 O). Methods: The rCBF R was quantified by kinetic modeling for FE-PE2I (R1) and H 2 O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls. Results: There was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731-0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001). Conclusions: Our results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBF R in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes.
Journal of Cerebral Blood Flow & Metabolism, 1988
The uptake and retention in a 2 cm thick brain section was recorded serially by SPECT after i. v. injec tion of [99mTc]-d,I-HM-PAO (HM-PAO). In 16 patients, the fraction of the administered dose retained by the brain was 5.2 ± 1%, showing a peak after 4�50s, then decreas ing by 10% within the first 10 min and then by only 0.4% per hour. The image contrast was measured in each pa tient as the regional hemispheric asymmetry difference in percent of the highest value of the two regions. It de ceased from 31 % at 3�0 s to 25% at 10 min. At 24 h, a value of 19% was reached. Using the images obtained at 10 min after injection, a region to region comparison of the original and corrected HM-PAO images to the x<!non-133 regional cerebral blood flow (rCBF) images was per formed, Forty-four patients with stroke, epilepsy, demen tia, basal ganglia disease, and tumors and control subjects were included in this comparison. The algorithm pro posed by Lassen et al. was used to correct the original images for back diffusion of tracer (brain to blood); a good correlation very close to the line of identity between the corrected HM-PAO and xenon-133 data was obtained when using a conversion/clearance ratio of 1.5 and when AR SPECT with [99mTc]-d, I-Hexamethyl-Propylene Amine Oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: Effects of linearization. J Cereb Blood Flow Metab 8(suppl I) :S82-S89
Journal of Cerebral Blood Flow & Metabolism, 2018
Phase-contrast mapping (PCM) magnetic resonance imaging (MRI) provides easy-access non-invasive quantification of global cerebral blood flow (gCBF) but its accuracy in altered perfusion states is not established. We aimed to compare paired PCM MRI and 15 O-H 2 O positron emission tomography (PET) measurements of gCBF in different perfusion states in a single scanning session. Duplicate combined gCBF PCM-MRI and 15 O-H 2 O PET measurements were performed in the resting condition, during hyperventilation and after acetazolamide administration (post-ACZ) using a 3T hybrid PET/ MR system. A total of 62 paired gCBF measurements were acquired in 14 healthy young male volunteers. Average gCBF in resting state measured by PCM-MRI and 15 O-H 2 O PET were 58.5 AE 10.7 and 38.6 AE 5.7 mL/100 g/min, respectively, during hyperventilation 33 AE 8.6 and 24.7 AE 5.8 mL/100 g/min, respectively, and post-ACZ 89.6 AE 27.1 and 57.3 AE 9.6 mL/100 g/min, respectively. On average, gCBF measured by PCM-MRI was 49% higher compared to 15 O-H 2 O PET. A strong correlation between the two methods across all states was observed (R 2 ¼ 0.72, p < 0.001). Bland-Altman analysis suggested a perfusion dependent relative bias resulting in higher relative difference at higher CBF values. In conclusion, measurements of gCBF by PCM-MRI in healthy volunteers show a strong correlation with 15 O-H 2 O PET, but are associated with a large and non-linear perfusion-dependent difference.
Journal of Cerebral Blood Flow & Metabolism, 1988
In order to validate the use of technetium-99m– d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a “linearization algorithm” to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF ( r = 0.901, p < 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.