scholarly journals Radiation Absorbed Dose to the Basal Ganglia from Dopamine Transporter Radioligand18F-FPCIT

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
William Robeson ◽  
Vijay Dhawan ◽  
Yilong Ma ◽  
David Bjelke ◽  
Claude Margouleff ◽  
...  

Our previous dosimetry studies have demonstrated that for dopaminergic radiotracers,18F-FDOPA and18F-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in the basal ganglia (BG) with high affinity and long residence times, radiation dose to the BG may become significant, especially in normal control subjects. We have performed dynamic PET measurements using18F-FPCIT in 16 normal adult subjects to determine if in fact the BG, although not a whole organ, but a well-defined substructure, receives the highest dose. Regions of interest were drawn over left and right BG structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations.S-factors were computed using the MIRDOSE3 nodule model for each caudate and putamen. For18F-FPCIT, BG dose ranged from 0.029 to 0.069 mGy/MBq. In half of all subjects, BG dose exceeded 85% of the published critical organ (bladder) dose, and in three of those, the BG dose exceeded that for the bladder. The BG can become the dose-limiting organ in studies using dopamine transporter ligands. For some normal subjects studied with F-18 or long half-life radionuclide, the BG may exceed bladder dose and become the critical structure.

2013 ◽  
Vol 4 (1) ◽  
pp. 21-26
Author(s):  
MN Islam ◽  
F Alam ◽  
MF Kabir ◽  
AS Mollah ◽  
MA Zaman

Radiation absorbed dose estimation was performed on eleven normal patients who were in a process of routine diagnostic investigation of the renal function. Bio-kinetics and bio-distribution of 99mTc-DTPA in patients was evaluated by dual-head gamma camera imaging and blood-plasma sample counting method. Radiation dose estimations were performed using standard MIRD techniques and biodistribution of different organ was estimated by drawing region of interest (ROI) according to MIRD phantom model [1]. From the time-activity curves, cumulative activities and residence times of 99mTc- DTPA in the kidneys, brain, upper large intestine (ULI), small intestine (SI), lower large intestine (LLI), stomach, heart, liver, lung and remainder of the body was calculated. Using the information of residence times of the total body and urinary bladder voiding at 2.4 hours on MIRD 12 absorbed dose for the 99mTc-DTPA in different target organs of the body was measured [2]. The estimated average absorbed dose to the kidneys as a target organ in normal Bangladeshis are 5.71E-03 mGy/MBq of 99mTc-DTPA which is closer to the ICRP 53 and other recent published data. The calculated effective dose equivalent and effective dose was found 5.72E-03 mSv/MBq and 4.89E-03 mSv/MBq respectively. DOI: http://dx.doi.org/10.3329/bjmp.v4i1.14674 Bangladesh Journal of Medical Physics Vol.4 No.1 2011 21-26


2006 ◽  
Vol 45 (03) ◽  
pp. 134-138 ◽  
Author(s):  
T. Kull ◽  
N. M. Blumstein ◽  
D. Bunjes ◽  
B. Neumaier ◽  
A. K. Buck ◽  
...  

SummaryAim: For the therapeutic application of radiopharmaceuticals the activity is determined on an individual basis. Here we investigated the accuracy for a simplified assessment of the residence times for a 188Re-labelled anti-CD66 monoclonal antibody. Patients, methods: For 49 patients with high risk leukaemia (24 men, 25 women, age: 44 ± 12 years) the residence times were determined for the injected 188Re-labelled anti-CD66 antibodies (1.3 ± 0.4 GBq, 5–7 GBq/mg protein, >95% 188Re bound to the antibody) based on 5 measurements (1.5, 3, 20, 26, and 44 h p.i.) using planar conjugate view gamma camera images (complete method). In a simplified method the residence times were calculated based on a single measurement 3 h p.i. Results: The residence times for kidneys, liver, red bone marrow, spleen and remainder of body for the complete method were 0.4 ± 0.2 h, 1.9 ± 0.8 h, 7.8 ± 2.1 h, 0.6 ± 0.3 h and 8.6 ± 2.1 h, respectively. For all organs a linear correlation exists between the residence times of the complete method and the simplified method with the slopes (correlation coefficients R > 0.89) of 0.89, 0.99, 1.23, 1.13 and 1.09 for kidneys, liver, red bone marrow, spleen and remainder of body, respectively. Conclusion: The proposed approach allows reliable prediction of biokinetics of 188Re-labelled anti-CD66 monoclonal antibody biodistribution with a single study. Efficient pretherapeutic estimation of organ absorbed dose may be possible, provided that a more stable anti-CD66 antibody preparation is available.


1979 ◽  
Vol 88 (1) ◽  
pp. 79-85 ◽  
Author(s):  
James W. Wolfe

Twenty-five normal subjects and 173 clinical patients received standard bithermal caloric testing. Vestibular nystagmus was evaluated for cumulative slow phase velocity from the summated horizontal eye recording and independent recording of the left and right eye. These data revealed that cold water stimulation produced more intense activation of the ipsilateral eye. Simultaneous closed-circuit video and D.C. electro-oculographic recordings from eight normal rhesus monkeys in response to cold water irrigations confirmed the fact that this stimulus leads to differential activation of the extraocular muscles. A possible explanation for this finding is discussed.


1983 ◽  
Vol 3 (4) ◽  
pp. 442-447 ◽  
Author(s):  
Lawrence C. McHenry ◽  
David A. Stump ◽  
George Howard ◽  
Thomas T. Novack ◽  
Don H. Bivins ◽  
...  

A single-blind study was conducted in 13 right-handed normal male subjects to compare the effects of oral and i.v. papaverine on regional cerebral blood flow (rCBF). Six xenon-133 inhalation rCBF measurements were performed on each subject; three tests—baseline, placebo, and drug evaluations—were carried out on each of two separate days. The oral and i.v. drugs were randomized for first-day administration. rCBF, measured as flow gray (FG), increased significantly (p ≤ 0.001) from baseline with both drug forms. Increases of 10.53% and 13.94% (left and right hemispheres, respectively) were demonstrated 90 min after a single 600-mg dose of oral papaverine. Increases of 5.09% and 8.69%, respectively, were recorded immediately after a single 100-mg dose of i. v. papaverine. FG also increased significantly (p ≤ 0.001) for both drug forms when compared to that of placebo. Placebo produced only a slight increase (not significant) with both the oral and i.v. groups. The data show that both oral and i.v. papaverine are equally effective in increasing rCBF in normal subjects.


2019 ◽  
Author(s):  
O. Ordu ◽  
A. Lusser ◽  
N. H. Dekker

ABSTRACTEukaryotic genomes are hierarchically organized into protein-DNA assemblies for compaction into the nucleus. Nucleosomes, with the (H3-H4)2 tetrasome as a likely intermediate, are highly dynamic in nature by way of several different mechanisms. We have recently shown that tetrasomes spontaneously change the direction of their DNA wrapping between left- and right-handed conformations, which may prevent torque build-up in chromatin during active transcription or replication. DNA sequence has been shown to strongly affect nucleosome positioning throughout chromatin. It is not known, however, whether DNA sequence also impacts the dynamic properties of tetrasomes. To address this question, we examined tetrasomes assembled on a high-affinity DNA sequence using freely orbiting magnetic tweezers. In this context, we also studied the effects of mono- and divalent salts on the flipping dynamics. We found that neither DNA sequence nor altered buffer conditions affect overall tetrasome structure. In contrast, tetrasomes bound to high-affinity DNA sequences showed significantly altered flipping kinetics, predominantly via a reduction in the lifetime of the canonical state of left-handed wrapping. Increased mono- and divalent salt concentrations counteracted this behaviour. Thus, our study indicates that high-affinity DNA sequences impact not only the positioning of the nucleosome, but that they also endow the subnucleosomal tetrasome with enhanced conformational plasticity. This may provide a means to prevent histone loss upon exposure to torsional stress, thereby contributing to the integrity of chromatin at high-affinity sites.STATEMENT OF SIGNIFICANCECanonical (H3-H4)2 tetrasomes possess high conformational flexibility, as evidenced by their spontaneous flipping between states of left- and right-handed DNA wrapping. Here, we show that these conformational dynamics of tetrasomes cannot be described by a fixed set of rates over all conditions. Instead, an accurate description of their behavior must take into account details of their loading, in particular the underlying DNA sequence. In vivo, differences in tetrasome flexibility could be regulated by modifications of the histone core or the tetrasomal DNA, and as such constitute an intriguing, potentially adjustable mechanism for chromatin to accommodate the torsional stress generated by processes such as transcription and replication.


Perception ◽  
1987 ◽  
Vol 16 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Jane M Pierson-Savage ◽  
John L Bradshaw

Vibrotactile reaction times in normal dextrals were measured for the two hands separately when either hand was located at each of seven possible positions: 90°, 45°, and 15° to the left and right of the chest midline, and at the midline itself (0°). Reaction times for the two hands did not differ and there was no Hand by Position interaction. At 90° left, reaction times were significantly slower than at any other position except 45° right. However, none of the other positions, including 45° right, differed from each other. Performance in this task, therefore, was relatively uniform from 90° right to 45° left, but markedly slower at 90° left. This far-left-side disadvantage may reflect a difficulty (for dextrals) in focussing covert attention in the far-left part of space for a block of trials. Since vibrotactile reaction times are sensitive to attentional factors in normal subjects, the paradigm should allow quantification of the clinical symptoms of the hemineglect syndrome; some preliminary observations of this syndrome with another vibrotactile design are reported.


Author(s):  
Azam Safir‐Mardanloo ◽  
Mani Khorsand Askari ◽  
Masoumeh‐ Lotfi Tokaldany ◽  
Mohammad Moein Ashrafi ◽  
Hakimeh Sadeghian

2020 ◽  
Vol 21 (21) ◽  
pp. 8216
Author(s):  
Tatyana D. Sotnikova ◽  
Evgeniya V. Efimova ◽  
Raul R. Gainetdinov

Dopamine transporter knockout (DATk) mice are known to demonstrate profound hyperactivity concurrent with elevated (5-fold) extracellular dopamine in the basal ganglia. At the same time, heterozygous DAT mice (DATh) demonstrate a 2-fold increase in dopamine levels yet only a marginal elevation in locomotor activity level. Another model of dopaminergic hyperactivity is the D3 dopamine receptor knockout (D3k) mice, which present only a modest hyperactivity phenotype, predominately manifested as stereotypical behaviors. In the D3k mice, the hyperactivity is also correlated with elevated extracellular dopamine levels (2-fold) in the basal ganglia. Cross-breeding was used to evaluate the functional consequences of the deletion of both genes. In the heterozygous DAT mice, inactivation of the D3R gene (DATh/D3k) resulted in significant hyperactivity and further elevation of striatal extracellular dopamine above levels observed in respective single mutant mice. The decreased weight of DATk mice was evident regardless of the D3 dopamine receptor genotype. In contrast, measures of thermoregulation revealed that the marked hypothermia of DATk mice (−2 °C) was reversed in double knockout mice. Thus, the extracellular dopamine levels elevated by prolonging uptake could be elevated even further by eliminating the D3 receptor. These data also suggest that the hypothermia observed in DATk mice may be mediated through D3 receptors.


2011 ◽  
Vol 26 (S2) ◽  
pp. 951-951
Author(s):  
E.N. Rizos ◽  
S. Chatziioannou ◽  
M. Kallergi ◽  
A. Douzenis ◽  
A. Apostolopoulos ◽  
...  

BackgroundTardive dyskinesia is a serious side effect of antipsychotics’ activity. Imaging of the dopamine transporter could demonstrate the possible involvement of dopaminergic pathway in the appearance of tardive dyskinesia.Methods/resultsWe report a case with paranoid schizophrenia and tardive dyskinesia symptoms. A first trial with quetiapine improved TD symptoms while an increase of its dose after a relapse of the underlying disease deteriorated the TD symptoms. Following that, sertindole was initiated which led to improvement of both psychotic and TD symptoms. A DAT scan showed physiologic distribution in the basal ganglia. Six months later after a serious cardiac syncope, sertindole was discontinued. Quetiapine was then started which led again to TD symptoms. A second DAT scan showed decreased dopamine transporter uptake in the area of basal ganglia.ConclusionWe conclude that decreased dopamine transporter uptake seemed to associate with the deterioration of TD.


Sign in / Sign up

Export Citation Format

Share Document