The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with 18F-fluorodeoxyglucose (FDG). This guideline will therefore address ...general information about 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information.
A major pathological hallmark of Alzheimer's disease is accumulation of amyloid-β in senile plaques in the brain. Evidence is accumulating that decreased clearance of amyloid-β from the brain may ...lead to these elevated amyloid-β levels. One of the clearance pathways of amyloid-β is transport across the blood-brain barrier via efflux transporters. P-glycoprotein, an efflux pump highly expressed at the endothelial cells of the blood-brain barrier, has been shown to transport amyloid-β. P-glycoprotein function can be assessed in vivo using (R)-11Cverapamil and positron emission tomography. The aim of this study was to assess blood-brain barrier P-glycoprotein function in patients with Alzheimer's disease compared with age-matched healthy controls using (R)-11Cverapamil and positron emission tomography. In 13 patients with Alzheimer's disease (age 65 ± 7 years, Mini-Mental State Examination 23 ± 3), global (R)-11Cverapamil binding potential values were increased significantly (P = 0.001) compared with 14 healthy controls (aged 62 ± 4 years, Mini-Mental State Examination 30 ± 1). Global (R)-11Cverapamil binding potential values were 2.18 ± 0.25 for patients with Alzheimer's disease and 1.77 ± 0.41 for healthy controls. In patients with Alzheimer's disease, higher (R)-11Cverapamil binding potential values were found for frontal, parietal, temporal and occipital cortices, and posterior and anterior cingulate. No significant differences between groups were found for medial temporal lobe and cerebellum. These data show altered kinetics of (R)-11Cverapamil in Alzheimer's disease, similar to alterations seen in studies where P-glycoprotein is blocked by a pharmacological agent. As such, these data indicate that P-glycoprotein function is decreased in patients with Alzheimer's disease. This is the first direct evidence that the P-glycoprotein transporter at the blood-brain barrier is compromised in sporadic Alzheimer's disease and suggests that decreased P-glycoprotein function may be involved in the pathogenesis of Alzheimer's disease.
Introduction
Several studies have shown the usefulness of positron emission tomography (PET) quantification using standardised uptake values (SUV) for diagnosis and staging, prognosis and response ...monitoring. Many factors affect SUV, such as patient preparation procedures, scan acquisition, image reconstruction and data analysis settings, and the variability in methodology across centres prohibits exchange of SUV data. Therefore, standardisation of 2-
18
F fluoro-2-deoxy-D-glucose (FDG) PET whole body procedures is required in multi-centre trials.
Methods
A protocol for standardisation of quantitative FDG whole body PET studies in the Netherlands (NL) was defined. This protocol is based on standardisation of: (1) patient preparation; (2) matching of scan statistics by prescribing dosage as function of patient weight, scan time per bed position, percentage of bed overlap and image acquisition mode (2D or 3D); (3) matching of image resolution by prescribing reconstruction settings for each type of scanner; (4) matching of data analysis procedure by defining volume of interest methods and SUV calculations and; (5) finally, a multi-centre QC procedure is defined using a 20-cm diameter phantom for verification of scanner calibration and the NEMA NU 2 2001 Image Quality phantom for verification of activity concentration recoveries (i.e., verification of image resolution and reconstruction convergence).
Discussion
This paper describes a protocol for standardization of quantitative FDG whole body multi-centre PET studies.
Conclusion
The protocol was successfully implemented in the Netherlands and has been approved by the Netherlands Society of Nuclear Medicine.
Up to 50% of curative surgery for suspected non-small-cell lung cancer is unsuccessful. Accuracy of positron emission tomography (PET) with 18-fluorodeoxyglucose (18FDG) is thought to be better than ...conventional staging for diagnosis of this malignancy. Up to now however, there has been no evidence that PET leads to improved management of patients in routine clinical practice. We did a randomised controlled trial in patients with suspected non-small-cell lung cancer, who were scheduled for surgery after conventional workup, to test whether PET with 18FDG reduces number of futile thoracotomies.
Before surgery (mediastinoscopy or thoracotomy), 188 patients from nine hospitals were randomly assigned to either conventional workup (CWU) or conventional workup and PET (CWU+PET). Patients were followed up for 1 year. Thoracotomy was regarded as futile if the patient had benign disease, explorative thoracotomy, pathological stage IIIA–N2/IIIB, or postoperative relapse or death within 12 months of randomisation. The primary outcome measure was futile thoracotomy. Analysis was by intention to treat.
96 patients were randomly assigned CWU and 92 CWU+PET. Two patients in the CWU+PET group did not undergo PET. 18 patients in the CWU group and 32 in the CWU+PET group did not have thoracotomy. In the CWU group, 39 (41%) patients had a futile thoracotomy, compared with 19 (21%) in the CWU+PET group (relative reduction 51%, 95% Cl 32–80%; p=0·003).
Addition of PET to conventional workup prevented unnecessary surgery in one out of five patients with suspected non-small-cell lung cancer.
Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ((11)Cdocetaxel). The objective of this study was to ...investigate whether a (11)Cdocetaxel PET microdosing study could predict tumor uptake of therapeutic doses of docetaxel.
Docetaxel-naïve lung cancer patients underwent 2 (11)Cdocetaxel PET scans; one after bolus injection of (11)Cdocetaxel and another during combined infusion of (11)Cdocetaxel and a therapeutic dose of docetaxel (75 mg·m(-2)). Compartmental and spectral analyses were used to quantify (11)Cdocetaxel tumor kinetics. (11)Cdocetaxel PET measurements were used to estimate the area under the curve (AUC) of docetaxel in tumors. Tumor response was evaluated using computed tomography scans.
Net rates of influx (Ki) of (11)Cdocetaxel in tumors were comparable during microdosing and therapeutic scans. (11)Cdocetaxel AUCTumor during the therapeutic scan could be predicted reliably using an impulse response function derived from the microdosing scan together with the plasma curve of (11)Cdocetaxel during the therapeutic scan. At 90 minutes, the accumulated amount of docetaxel in tumors was less than 1% of the total infused dose of docetaxel. (11)Cdocetaxel Ki derived from the microdosing scan correlated with AUCTumor of docetaxel (Spearman ρ = 0.715; P = 0.004) during the therapeutic scan and with tumor response to docetaxel therapy (Spearman ρ = -0.800; P = 0.010).
Microdosing data of (11)Cdocetaxel PET can be used to predict tumor uptake of docetaxel during chemotherapy. The present study provides a framework for investigating the PET microdosing concept for radiolabeled anticancer drugs in patients.
Background
Patients with colorectal liver metastases (CRLM) who are ineligible for curative surgery are potential candidates for radiofrequency ablation (RFA). Although RFA has emerged as a well ...accepted and documented treatment modality, there are still some reservations because of initially high rates of local site recurrences (LSR). The aim of the present study was to evaluate LSR levels following RFA treatment, with a specific focus on re-treatment and survival.
Patients and methods
All patients ineligible for curative resection of CRLM and undergoing RFA alone or in combination with resection were prospectively included from July 2000 to December 2010 and retrospectively analyzed. Patients with untreatable extrahepatic disease were excluded. FDG PET–CT was conducted at 3–6 month intervals after RFA. Patients with LSR were evaluated for re-treatment.
Results
A total of 132 patients were treated with RFA, which was combined with resection in 64 patients. A total of 290 lesions were ablated, with a mean number of 2.19 per patient and a mean size of 2.2 cm. Median survival was 41 months, with a 3- and 5-year survival of, respectively, 60 and 30.8 %. Following initial RFA, 39 patients developed an LSR in 40 ablated lesions, and local recurrence was strongly related to lesion size. Re-treatment could be performed in 26/39 patients, of whom eight remained disease-free.
Conclusions
Radiofrequency ablation can be applied to CRLM of less than 3 cm with curative intent. In the absence of extensive intrahepatic or extrahepatic disease, renewed treatment of local recurrences should be considered and is often successful.
Patients with an elevated erythrocyte sedimentation rate (ESR) and non-specific symptoms often pose a diagnostic dilemma. PET/CT visualises infection, inflammation and malignancy, all of which may ...cause elevated ESR. The objective of this study was to determine the contribution of 18F-fluorodeoxglucose positron emission tomography (PET/CT) in the diagnostic work-up of referred patients with an elevated ESR, in whom initial routine evaluation did not reveal a diagnosis. We conducted a combined retrospective (A) and prospective (B) study in elderly (>50 years) patients with a significantly elevated ESR of ≥ 50 mm/h and non-specific complaints. In study A, 30 patients were included. Malignancy (8 patients), auto-inflammatory disease (8 patients, including 5 with large-vessel vasculitis) and infection (3 patients) were suggested by PET/CT. Two scans showed non-specific abnormalities and 9 scans were normal. Of the 21 abnormal PET/CT results, 12 diagnoses were independently confirmed and two alternative diagnosis were made. Two diagnoses were established in patients with a normal scan. In study B, 58 patients in whom a prior protocolised work-up was non-diagnostic, were included. Of these, 25 PET/CT-scans showed suspected auto-inflammatory disease, particularly large-vessel vasculitis (14 cases). Infection and malignancy was suspected in 5 and 3 cases, respectively. Seven scans demonstrated non-specific abnormalities, 20 were normal. Of the 40 abnormal PET/CT results, 22 diagnoses were confirmed, 3 alternative diagnoses were established. Only one diagnosis was established in the 20 patients with a normal scan. In both studies, the final diagnosis was based on histology, clinical follow-up, response to therapy or additional imaging. In conclusion, PET/CT may be of potential value in the diagnostic work-up of patients with elevated ESR if routine evaluation reveals no diagnosis. In particular, large-vessel vasculitis appears to be a common finding. A normal PET/CT scan in these patients suggests that it is safe to follow a wait-and-see policy.
Purpose
Major depressive disorder (MDD) has been related to both a dysfunctional γ-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although ...GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GABA
A
-benzodiazepine receptor in depressed patients or in relation to antidepressant treatment.
Methods
Eleven depressed outpatients were compared, before and after treatment with citalopram, with nine age-matched healthy controls. The subjects were scanned using the positron emission tomography (PET) tracer
11
Cflumazenil (
11
CFMZ). Parametric voxel-by-voxel Logan plots were compared with methods based on regions of interest (ROI), to provide volume of distribution (V
T
) and binding potential (BP
ND
) values. Plasma GABA levels were determined and a dexamethasone-corticotropin releasing hormone (DEX-CRH) test was performed.
Results
In MDD, parametric voxel-by-voxel Logan plots showed bilateral reduced
11
CFMZ binding in the parahippocampal gyrus and right lateral superior temporal gyrus (
p
uncorrected ≤0.001). In the temporal area,
11
CFMZ binding showed a strong inverse correlation with HPA axis activity. Plasma GABA did not discriminate MDD from controls, but correlated inversely with
11
CFMZ binding in the right insula. Following treatment with citalopram, voxel-based analysis revealed reduced binding in the right lateral temporal gyrus and dorsolateral prefrontal cortex.
Conclusion
The bilateral reduction in limbic parahippocampal and right temporal
11
CFMZ binding found in MDD indicates decreased GABA
A
-benzodiazepine receptor complex affinity and/or number. The inverse relationship between GABA
A
binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition.
To perform a meta-analysis to obtain sensitivity estimates of computed tomography (CT), magnetic resonance (MR) imaging, and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) ...for detection of colorectal liver metastases on per-patient and per-lesion bases.
MEDLINE, EMBASE, Web of Science, and CANCERLIT databases and Cochrane Database of Systematic Reviews were searched for relevant original articles published from January 1990 to December 2003. Criteria for inclusion of articles were as follows: Articles were reported in the English, German, or French language; CT, MR imaging, or FDG PET was performed to identify and characterize colorectal liver metastases; histopathologic analysis (surgery, biopsy, or autopsy), intraoperative observation (manual palpatation, intraoperative ultrasonography US), and/or follow-up US was the reference standard; and data were sufficient for calculation of true-positive or false-negative values. A random-effects linear regression model was used to obtain sensitivity estimates in assessment of liver metastases.
Of 165 identified relevant articles, 61 fulfilled all inclusion criteria. Sensitivity estimates on a per-patient basis for nonhelical CT, helical CT, 1.5-T MR imaging, and FDG PET were 60.2%, 64.7%, 75.8%, and 94.6%, respectively; FDG PET was the most accurate modality. On a per-lesion basis, sensitivity estimates for nonhelical CT, helical CT, 1.0-T MR imaging, 1.5-T MR imaging, and FDG PET were 52.3%, 63.8%, 66.1%, 64.4%, and 75.9%, respectively; nonhelical CT had lowest sensitivity. Estimates of gadolinium-enhanced MR imaging and superparamagnetic iron oxide (SPIO)-enhanced MR imaging were significantly better, compared with nonenhanced MR imaging (P = .019 and P < .001, respectively) and with helical CT with 45 g of iodine or less (P = .02 and P < .001, respectively). For lesions of 1 cm or larger, SPIO-enhanced MR imaging was the most accurate modality (P < .001).
FDG PET had significantly higher sensitivity on a per-patient basis, compared with that of the other modalities, but not on a per-lesion basis. Sensitivity estimates for MR imaging with contrast agent were significantly superior to those for helical CT with 45 g of iodine or less.
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