scholarly journals Effects of rapid tryptophan depletion on brain 5-HT2receptors: a PET study

2001 ◽  
Vol 178 (5) ◽  
pp. 448-453 ◽  
Author(s):  
Lakshmi N. Yatham ◽  
Peter F. Liddle ◽  
I-Shin Shiah ◽  
Raymond W. Lam ◽  
Michael J. Adam ◽  
...  

BackgroundThe mechanism by which rapid tryptophan depletion (RTD) paradigm induces depressive relapse in recently remitted patients with depression is unknown.AimsTo determine the effects of RTD on brain 5-HT2receptors using positron emission tomography (PET) and18F-labelled setoperone.MethodTen healthy women underwent two PET scans. Each scan was done 5 h after the ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and the two test sessions were separated by at least 5 days.ResultsThe RTD decreased plasma free tryptophan levels significantly but it had no significant effects on mood. Subjects showed a significant decrease in brain 5-HT2receptor binding in various cortical regions following the RTD session.ConclusionsWhen taken with the evidence that antidepressant treatment is associated with a decrease in brain 5-HT2receptors, these findings suggest that a decrease in 5-HT2binding following RTD might be an adaptive response that provides protection against depressive symptoms.

2011 ◽  
Vol 199 (5) ◽  
pp. 391-397 ◽  
Author(s):  
Sylvia M. L. Cox ◽  
Chawki Benkelfat ◽  
Alain Dagher ◽  
J. Scott Delaney ◽  
France Durand ◽  
...  

BackgroundLow serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.AimsTo investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.MethodIn non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [11C]raclopride.ResultsAcute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine.ConclusionsThe results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.


2015 ◽  
Vol 35 (5) ◽  
pp. 743-746 ◽  
Author(s):  
Martin Bauer ◽  
Rudolf Karch ◽  
Markus Zeitlinger ◽  
Cécile Philippe ◽  
Kerstin Römermann ◽  
...  

As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate ( R)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume ( VT) of ( R)-[11C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
David Dudoignon ◽  
David A. Pattison ◽  
Damien Legallois ◽  
Rodney J. Hicks ◽  
Nicolas Aide

Abstract Background Positron Emission Tomography with Computed Tomography (PET/CT) is widely used in the assessment of many diseases, particularly including cancer. However, many factors can affect image quality and diagnostic performance of PET scans using FDG or other PET probes. Main body The aim of this pictorial essay is to review PET/CT protocols that can be useful to overcome these confounding factors in routine clinical situations, with a particular focus on pharmacological interventions and problem-oriented CT acquisition protocols. Conclusion Imaging protocols and representative cases will be discussed, in addition to potential contraindications and precautions to be taken.


2002 ◽  
Vol 96 (2) ◽  
pp. 263-268 ◽  
Author(s):  
Arun K. Gupta ◽  
Peter J. Hutchinson ◽  
Tim Fryer ◽  
Pippa G. Al-Rawi ◽  
Dot A. Parry ◽  
...  

Object. The benefits of measuring cerebral oxygenation in patients with brain injury are well accepted; however, jugular bulb oximetry, which is currently the most popular monitoring technique used has several shortcomings. The goal of this study was to validate the use of a new multiparameter sensor that measures brain tissue oxygenation and metabolism (Neurotrend) by comparing it with positron emission tomography (PET) scanning. Methods. A Neurotrend sensor was inserted into the frontal region of the brain in 19 patients admitted to the neurointensive care unit. After a period of stabilization, the patients were transferred to the PET scanner suite where C15O, 15O2, and H215O PET scans were obtained to facilitate calculation of regional cerebral blood volume, O2 metabolism, blood flow, and O2 extraction fraction (OEF). Patients were given hyperventilation therapy to decrease arterial CO2 by approximately 1 kPa (7.5 mm Hg) and the same sequence of PET scans was repeated. For each scanning sequence, end-capillary O2 tension (PvO2) was calculated from the OEF and compared with the reading of brain tissue O2 pressure (PbO2) provided by the sensor. In three patients the sensor was inserted into areas of contusion and these patients were eliminated from the analysis. In the subset of 16 patients in whom the sensor was placed in healthy brain, no correlation was found between the absolute values of PbO2 and PvO2 (r = 0.2, p = 0.29); however a significant correlation was obtained between the change in PbO2 (ΔPbO2) and the change in PvO2 (ΔPvO2) produced by hyperventilation in a 20-mm region of interest around the sensor (ρ = 0.78, p = 0.0035). Conclusions. The lack of correlation between the absolute values of PbO2 and PvO2 indicates that PbO2 cannot be used as a substitute for PvO2. Nevertheless, the positive correlation between ΔPbO2 and ΔPvO2 when the sensor had been inserted into healthy brain suggests that tissue PO2 monitoring may provide a useful tool to assess the effect of therapeutic interventions in brain injury.


Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3340-3346 ◽  
Author(s):  
Robert Carr ◽  
Sally F. Barrington ◽  
Bella Madan ◽  
Michael J. O'Doherty ◽  
Catherine A.B. Saunders ◽  
...  

Abstract Positron emission tomography (PET) is a whole-body imaging technique using 18 fluorine-fluorodeoxyglucose (FDG), whose uptake is increased in tumor cells. Published studies have shown PET to be an effective method of staging lymphoma and to be more sensitive than CT at detecting extranodal disease. The purpose of this study was to determine whether the increased marrow uptake of FDG observed in some lymphoma patients during routine staging PET scans represented marrow involvement by disease. PET scans of 50 patients with Hodgkin's (12) and non-Hodgkin's (38) lymphoma were analyzed by three independent observers and the marrow graded as normal or abnormal using a visual grading system. Unilateral iliac crest marrow aspirates and biopsies were performed on all patients. The PET scan and marrow histology agreed in 39 patients (78%), being concordant positive in 13 and concordant negative in 26 patients. In 8 patients the PET scan showed increased FDG uptake but staging biopsy was negative; in 4 of these 8 patients the PET scan showed a normal marrow background with focal FDG “hot spots” distant from the site biopsied. In 3 patients the marrow biopsy specimen was positive but the PET scan normal; 2 of these 3 patients had non-Hodgkin's lymphoma whose malignant cells did not take up FDG at lymph node or marrow disease sites. Therefore, there were only 5 patients (10%) in whom there was a difference between the PET scan and biopsy result which could not be fully explained. Visual interpretation of marrow FDG uptake during whole-body staging PET scans can correctly assess marrow disease status in a high proportion of lymphoma patients. PET has the potential to reduce the need for staging marrow biopsy.


2007 ◽  
Vol 137 (3) ◽  
pp. 400-404 ◽  
Author(s):  
Deanne L. King ◽  
Brendan C. Stack ◽  
Paul M. Spring ◽  
Ronald Walker ◽  
Donald L. Bodenner

OBJECTIVE: Fluorodeoxyglucose (FDG) whole body positron emission tomography (PET) scan may show clinically occult second lesions. Such lesions in the thyroid are increasingly common. There are several recent reports of a high probability of malignancy in these lesions ranging from 14% to 63%. STUDY DESIGN AND SETTING: This is a retrospective review of 15,711 PET scans at a multi-disciplinary thyroid clinic at a tertiary care university medical center. Twenty-two patients were referred with thyroid PET “incidentalomas.” The review included 18 FDG-PET scans, ultrasound guided fine needle aspiration biopsies, and thyroid surgery pathology. Aspiration cytology or pathology were the main outcome measures. RESULTS: Three patients had malignancy of the PET-positive thyroid lesions. Papillary thyroid micro carcinomas were detected in four of the specimens that showed a benign pathology of the dominant nodule. CONCLUSION: Our experience shows a 14% malignancy rate for the dominant (imaged) nodule and a total malignancy rate of 32% when the incidental micro carcinomas are included. Both of these rates are significantly lower than results published previously.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3039-3039 ◽  
Author(s):  
Anna Dodero ◽  
Roberto Crocchiolo ◽  
Francesca Patriarca ◽  
Fabio Ciceri ◽  
Nicolo’ Frungillo ◽  
...  

Abstract Positron emission tomography (PET) scan using 18-fluorodeoxyglucose [18F-FDG] has a prognostic value in patients (pts) with Hodgkin Lymphoma (HL) or aggressive Non-Hodgkin lymphoma (NHL) receiving chemotherapy. Chemosensitive disease is a critical prognostic factor for the success of both autologous and allogeneic stem cell transplantation (allo-SCT). We have recently shown a lower risk of death or progression for pts in CR versus those in PR before reduced-intensity conditioning (RIC) allo-SCT (Corradini P, Leukemia 2007). Thus, to better assess the value of pre-transplant disease response, we retrospectively assessed the prognostic role of PET scan before allotransplant. Between 2000 and 2007, 64 consecutive patients with a histologically proven diagnosis of aggressive NHL [n=30: diffuse large B cell lymphoma (n=18), peripheral T-cell lymphomas (n=11), Burkitt lymphoma (n=1)] or HL [n=34], responding to salvage therapy, were evaluated with a PET scan before and after allo-SCT. PET scans were performed at 3 different Nuclear Medicine Units. Presence (PET-positive) or absence (PET-negative) of abnormal 18F-FDG uptake was correlated to progression-free survival (PFS) and overall survival (OS) curves. Patients’ median age was 37 years (range, 17–65 years). Thirty-three pts (52%) were allografted from a HLA-identical sibling donor, 14 from a haploidentical donor and 17 from an unrelated donor. Pts had relapsed disease: 52 pts (81%) had failed autologous SCT, the median number of prior chemotherapy regimens was 3 (range, 1–6). All pts received a RIC regimen followed by allo-SCT. PET scans were performed at a median of 30 days prior to allograft (range, 3–90 days): 34 out of 64 pts showed an abnormal 18F-FDG uptake [NHL (n=16), HL (n=18)] whereas 30 were completely negative [NHL (n=14), HL (n=16)]. Patients with PET-positive or PET-negative scans were balanced in terms of diagnosis, previous treatments, and type of donor. At a median follow-up of 24 months (range, 6–86 months), 41 pts are alive and 23 died [toxicity n=10 (n= 5 NHL, n=5 HL), disease n=13 (n=8 NHL, n=5 HL)]. Overall, the estimated 3-year PFS in pts with negative or positive PET scans were 64% (95% CI, 42%–86%) versus 28% (95% CI, 8%–48%), respectively (p<0.005). A statistically significant higher cumulative risk of relapse was observed in pts with a positive PET scan before allografting as compared to the PET negatives (53% versus 21%, p< 0.022). The estimated 3-year OS in pts with negative or positive PET scans were 69% (95% CI; 51%–87%) versus 44% (95% CI;23%-65%), respectively (p=0.05). For NHL pts, the estimated 3-year PFS was 59% for PET-negative as compared to 38% for PET-positive (p<0.04). For HL pts, the estimated 3-year PFS was 70% for PET-negative as compared to 23% for PET-positive (p<0.05). PET scan has a clinical relevance before allo-SCT. Pts with a positive PET scan have a worse outcome, and should receive experimental therapies to target chemoresistant tumor cells.


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