Comparison of diagnostic accuracy of (111)In-pentetreotide SPECT and (68)Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours.

OBJECTIVES: To compare the diagnostic accuracy of (111)In-pentetreotide-scintigraphy with (68)Ga-DOTATOC-positron emission tomography (PET)/computed tomography (CT) in patients with metastatic-neuroendocrine tumour (NET) scheduled for peptide receptor radionuclide therapy (PRRT). Incremental lesions (ILs) were defined as lesions observed on only one modality. METHODS: Fifty-three metastatic-NET-patients underwent (111)In-pentetreotide-scintigraphy (24 h post-injection; planar+single-photon emission CT (SPECT) abdomen) and whole-body (68)Ga-DOTATOC-PET/CT. SPECT and PET were compared in a lesion-by-lesion and organ-by-organ analysis, determining the total lesions and ILs for both modalities. RESULTS: Significantly more lesions were detected on (68)Ga-DOTATOC-PET/CT versus (111)In-pentetreotide-scintigraphy. More specifically, we observed 1,098 lesions on PET/CT (range: 1-105; median: 15) versus 660 on SPECT (range: 0-73, median: 9) (p<0.0001), with 439 PET-ILs (42/53 patients) and one SPECT-IL (1/53 patients). The sensitivity for PET/CT was 99.9 % (95 % CI, 99.3-100.0), for SPECT 60.0 % (95 % CI, 48.5-70.2). The organ-by-organ analysis showed that the PET-ILs were most frequently visualized in liver and skeleton. CONCLUSION: Ga-DOTATOC-PET/CT is superior for the detection of NET-metastases compared to (111)In-pentetreotide SPECT. KEY POINTS: Somatostatin receptor PET is superior to SPECT in detecting NET metastases. PET is the scintigraphic method for accurate depiction of NET tumour burden. The sensitivity of PET is twofold higher than the sensitivity of SPECT.

Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial.

OBJECTIVE: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure. DESIGN: Single centre double-blind randomized placebo controlled trial. SETTING: Cardiac rehabilitation centre. SUBJECTS AND INTERVENTION: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation. MAIN MEASURES: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed. RESULTS: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P<0.05 for all). However, changes after training were similar between placebo group and creatine group (P>0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects. CONCLUSION: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone.

An unusual case of 4-aminopyridine toxicity in a multiple sclerosis patient: epileptic disorder or toxic encephalopathy?

We report the case of a 45-year old female multiple sclerosis patient, who accidentally was overdosed with 4-aminopyridine which resulted in dystonic, choreathetoid type abnormal movements in the four limbs, motoric distress, confusion and opisthotonus. There is little known about 4-aminopyridine toxicity. There are only a few reported cases ranging from mild paresthesias to tonic-clonic seizures. 4-aminopyridine enhances neuronal conduction at neuromuscular synapses and is indicated in the treatment of selected neurological disorders including multiple sclerosis (MS) and myasthenia gravis, among others.

Molecular imaging of prostate cancer.

Prostate carcinoma is the most common non-cutaneous malignancy in males. Imaging of prostatic lesions is of great importance and aids in oncologic management and monitoring of therapy response. Particularly molecular imaging based on positron emission tomography (PET) and single photon emission computerized tomography (SPECT) has great potential. Using radio-labelled molecular probes, these approaches are highly sensitive and can provide key molecular and functional information on tumours. The identification of suitable targets based on unique genetic and biochemical features of cancer lesions is one of the core activities driving progress in molecular imaging of pathological processes. Nowadays, mainly metabolic probes are being used routinely for detection and staging of prostate cancer. The development of new specific receptor ligands and targeted probes and antibodies holds great promise to further enhance the performance of molecular imaging and to further improve the diagnosis and monitoring of prostate cancer.

Non-Hodgkin lymphoma: retrospective study on the cost-effectiveness of early treatment response assessment by FDG-PET.

PURPOSE: Although lymphomas are very chemosensitive, 50% of patients with aggressive non-Hodgkin lymphoma (NHL) are not cured with standard first-line treatment. This consists of six cycles of doxorubicin, vincristine, prednisolone and cyclophosphamide (CHOP), recently complemented with rituximab. Preliminary studies show that PET mid-treatment is a good predictor of the remission status at the end of therapy. As patients with persistent FDG uptake after three cycles are unlikely to gain a complete remission, the remaining three cycles of chemotherapy are useless. We investigated the costs and benefits for the use of PET in this early treatment setting. METHODS: We conceived a model using a conventional arm where patients receive the full regimen of six cycles of CHOP [-rituximab] and an experimental algorithm where patients receive either six cycles (PET response) or only three cycles (PET non-response). Based on a patient sample (2004-2006), we calculated the costs for hospitalisation and treatment. We took into account all costs accrued (including overhead costs). We used a sensitivity analysis by varying the most important parameters. RESULTS: With a PET price of 700 euro and CHOP price (per cycle) of 1,829 euro , we can conclude to cost saving of 1,879 euro per patient. The PET price can increase up to 2,580 euro and the cost for one cycle of CHOP can decrease to 500 euro per cycle before cost savings are nil. The percentage of non-responders may be as low as 10%. The implementation of rituximab in first-line therapy only increases benefit (4,900 euro/pt). CONCLUSION: We conclude to substantial cost savings if management of NHL patients is based on mid-treatment PET scan. The economical data we used seem to be comparable to those published in other European studies. Implementation of Mabthera in first line only increases cost savings.

Synthesis and evaluation of a (99m)Tc-BAT-phenylbenzothiazole conjugate as a potential in vivo tracer for visualization of amyloid beta.

We have conjugated S,S'-bis-trityl-N-BOC-N'-acetic acid-1,2-ethylenedicysteamine, a protected bis-amino-bis-thiol (BAT) tetraligand, with 2-(4'-aminophenyl)-1,3-benzothiazole, a derivative of thioflavin-T with known affinity for amyloid. The conjugate was efficiently labelled with (99m)Tc by heating of the protected precursor in diluted hydrochloric acid followed by neutralization and heating in the presence of (99m)Tc-tartrate. It was demonstrated that the (99m)Tc-BAT-phenylbenzothiazole conjugate binds in vitro to amyloid beta present in postmortem brain slices of Alzheimer's patients. Despite its high lipophilicity and neutral character, the radiolabelled conjugate did not cross the blood-brain barrier to a sufficient degree and therefore is not useful for detection of Alzheimer's disease. Further evaluation of this (99m)Tc-labelled tracer agent could elucidate its potential usefulness to visualize amyloid plaques in peripheral amyloidosis.

Takayasu's arteritis in a young Caucasian female: case report and review.

We report a case of a 24-year-old Caucasian woman presenting with fatigue, weight loss, a cardiac murmur, anaemia and biochemical markers of inflammation due to Takayasu's arteritis (TA), a vasculitis of the aorta and large vessels that typically affects young women. The rarity of the disease, the great variability in presentation together with the absence of specific symptoms as well as the absence of specific biochemical markers, makes early diagnosis difficult. Besides (magnetic resonance) arteriography, new promising diagnostic tools are discussed, including transoesophageat echocardiography (TEE) and Positron Emission Tomography (PET). Nevertheless, a high index of suspicion remains the key to an early diagnosis, and hence a better prognosis, of TA.

Additional value of PET-CT in the staging of lung cancer: comparison with CT alone, PET alone and visual correlation of PET and CT.

Integrated positron emission tomography (PET) and computed tomography (CT) is a new imaging modality offering anatomic and metabolic information. The purpose was to evaluate retrospectively the accuracy of integrated PET-CT in the staging of a suggestive lung lesion, comparing this with the accuracy of CT alone, PET alone and visually correlated PET-CT. Fifty patients undergoing integrated PET-CT for staging of a suggestive lung lesion were studied. Their tumor, node, metastasis (TNM) statuses were determined with CT, PET, visually correlated PET-CT and integrated PET-CT. These TNM stages were compared with the surgical TNM status. Integrated PET-CT was the most accurate imaging technique in the assessment of the TNM status. Integrated PET-CT predicted correctly the T status, N status, M status and TNM status in, respectively, 86%, 80%, 98%, 70% versus 68%, 66%,88%, 46% with CT, 46%, 70%, 96%, 30% with PET and 72%, 68%, 96%, 54% with visually correlated PET-CT. T status and N status were overstaged, respectively, in 8% and 16% with integrated PET-CT, in 20% and 28% with CT, in 16% and 20% with PET, in 12% and 20% with visually correlated PET-CT and understaged in 6% and 4% with integrated PET-CT, versus 12% and 6% with CT, 38% and 10% with PET and 12% with visually correlated PET-CT. Integrated PET-CT improves the staging of lung cancer through a better anatomic localization and characterization of lesions and is superior to CT alone and PET alone. If this technique is not available, visual correlation of PET and CT can be a valuable alternative.

Repetitive 18-fluorodeoxyglucose positron emission tomography in isolated polymyalgia rheumatica: a prospective study in 35 patients.

OBJECTIVE: To study fluorodeoxyglucose (FDG) deposition in different vascular beds and in the large joints of patients with isolated polymyalgia rheumatica (PMR), and to investigate whether there is a relation between FDG-positron emission tomography (PET) results and risk of relapse. METHODS: All consecutive patients with isolated PMR underwent a FDG-PET scan before treatment with steroids was started and--if logistics allowed--at 3 and 6 months. PET scans were scored at seven different vascular areas and a total vascular score (TVS) was calculated, ranging from 0 to 21. FDG uptake in the shoulders, the hips and the processi spinosi of the vertebrae was scored as 0 (no uptake), 1 (moderate uptake) or 2 (intense uptake). RESULTS: Thirty-five patients entered the study. At diagnosis, vascular FDG uptake was noted in 11 patients (31%), predominantly at the subclavian arteries. Mean TVS was low. FDG uptake in the shoulders was noted in 94% of patients, in the hips in 89% and in the processi spinosi of the vertebrae in 51%. The intensity of FDG uptake in the large vessels or in the shoulders, hips or processi spinosi did not correlate with the risk of relapse. CONCLUSIONS: Only one in three patients has an (moderately) increased vascular FDG uptake, especially in the subclavian arteries. The vast majority has inflammation of shoulders and hips, and half of them have increased FDG-uptake at the processi spinosi. Results of FDG-PET scans in patients with PMR did not correlate with their risk of relapse.

[11C]methionine PET, histopathology, and survival in primary brain tumors and recurrence.

BACKGROUND AND PURPOSE: [(11)C]Methionine (MET) PET imaging is a sensitive technique for visualizing primary brain tumors and recurrence/progression after therapy. The aim of this study was to evaluate the relationship between the uptake of MET and histopathologic grading and to investigate the prognostic value of the tracer, in both settings. METHODS: Cerebral uptake of MET was determined in 52 patients: in 26 patients for primary staging (group A) and 26 patients with suspected brain tumor recurrence/progression after therapy (group B). Semiquantitative methionine uptake indices (UI) defined by the tumor (maximum)-to-background ratio was correlated with tumor grade and final outcome. RESULTS: Overall median survival was 34.9 months. MET showed pathologically increased uptake in 41 of 52 scans. Although a weak linear correlation between MET uptake and grading was observed (R = 0.38, P = .028), analysis of variance showed no significant differences in MET UI between tumor grades for either group A or B. Benign and grade I lesions showed significant difference in MET uptake in comparison with higher grade lesions (P = .006). Using Kaplan-Meier survival analysis, no thresholds could be found at which MET was predictive for survival. Proportional hazard regression showed that only WHO grading class (low versus high) was predictive of survival (P = .015). CONCLUSION: Interindividual MET uptake variability does not allow noninvasive grading on an individual patient basis. Moreover, there is no significant prognostic value in studying maximal methionine UI in brain tumors. The clinical use of MET should therefore be primarily focused on questions such as detection of recurrence, biopsy guidance, and radiation therapy target volume delineation.

FDG-PET for preoperative staging of bladder cancer.

PURPOSE: The presence of lymph node involvement (N) and distant metastasis (M) in patients with invasive bladder carcinoma is a major determinant of survival and, therefore, a pivotal element in the therapeutic management. The aim of this prospective study was to evaluate the use of( 18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in this indication. METHODS: Whole-body FDG-PET and computed tomography (CT) were performed in 55 patients with non-metastatic invasive bladder cancer for preoperative staging. Correlative imaging of PET with CT was performed, leading to a PET(CT) result. The imaging results were compared with the gold standard, consisting of histopathology (lymphadenectomy, guided biopsy) or clinical follow-up for 12 months, and related to overall survival using the Kaplan-Meier method. RESULTS: The gold standard was available in 40 patients and indicated NM-positive disease in 15 patients (12 N lesions, 8 M lesions), and NM-negative disease in 25 patients. For the diagnosis of NM-positive disease, the sensitivity, specificity and accuracy of PET(CT) were 60%, 88% and 78%, respectively. Diagnostic discordances between PET(CT) and CT alone were found in 9/40 patients, among whom PET was correct in six (15%): three with true-positive and one with true-negative distant metastases, and two with true-negative lymph nodes. Median survival time of patients in whom PET(CT) indicated NM-positive disease was 13.5 months, compared with 32.0 months in the patients with a NM-negative PET(CT) (p=0.003). CONCLUSION: Addition of metabolism-based information provided by FDG-PET to CT in the preoperative staging of invasive bladder carcinoma yields a high diagnostic and prognostic accuracy.

Cost-effectiveness of 18F-fluorodeoxyglucose positron emission tomography in the assessment of early dementia from a Belgian and European perspective.

(18)F-fluoro-deoxyglucose positron emission tomography (FDG PET) can aid to predict AD in an early stage. The aim of this study was to estimate the economic effects of incorporating FDG PET in the diagnostic work-up of AD in a Belgian and European setting. A decision tree analysis was followed comparing a conventional algorithm using diagnostic clinical criteria and one that also incorporates PET. Major outcome terms were overall cost per patient in either strategy; diagnostic accuracy and cost per accurate diagnosis. A sensitivity analysis was performed for four critical variables: cost of PET, sensitivity and specificity of PET and delay in cognitive decline because of appropriate medication. Cost-savings per accurate diagnosis ranged from 623-6110 Euro in favour of the proposed algorithm with PET. For the same cost, more accurate diagnoses were made, resulting in benefit for patients and society. The positive results were maintained over a wide range of values for the critical variables and were expandable to other European countries with a similar health system. Therefore, incorporation of FDG PET into the clinical diagnostic work up of patients with early symptoms of cognitive decline can be advocated.

Mucociliary transport using 99mTc-albumin colloid: a reliable screening test for primary ciliary dyskinesia.

BACKGROUND: A study was undertaken to assess the reliability of the nasal mucociliary transport test using 99mTc-albumin colloid as a screening test for primary ciliary dyskinesia (PCD) and to compare it with the gold standard nasal biopsy for study of ciliary motility and ultrastructure. METHODS: During a 4 year period both tests were performed in 55 children referred with persistent or recurrent respiratory tract infections. Their median age was 4 years (range 1 month to 15 years). RESULTS: The nasal biopsy results were as follows: PCD, n = 8; secondary ciliary dyskinesia (SCD), n = 19; normal, n = 28. The mucociliary transport test was abnormal in 29 patients (all 8 with PCD, 7/19 with SCD, and 14/28 with a normal biopsy). The sensitivity of the mucociliary transport test to diagnose PCD was therefore 100% (8/8) (95% exact confidence limits 63.06 to 100.00); the specificity was only 55% (26/47) (40.95 to 69.89). The negative predictive value was 100% (26/26) (86.77 to 100.00) and the positive predictive value was 28% (8/29) (12.37 to 47.24). CONCLUSION: Mucociliary transport is a non-invasive screening test that can be performed even in infants. The sensitivity of the test is high but its specificity is low. A normal test result excludes PCD.

Colloid carcinoma arising in an anorectal fistula in Crohn's disease: a case report.

Carcinoma arising in a chronic anorectal fistula in Crohn's disease is rare, but the association has been reported in the literature. In most cases, it concerns a colloid carcinoma. Probably chronic irritation at either end of a fistula can trigger the degeneration of scar tissue into cancer. The diagnosis is difficult, due to lack of specificity of symptoms and signs, and is often delayed, resulting in a poor prognosis. A 70-year-old female, diagnosed with Crohn's disease at the age of 45, developed a pararectal colloid carcinoma in an anorectal fistula that had existed for years. She was treated with an abdominoperineal resection and adjuvant chemotherapy (5-fluorouracil and levofolinate) but died. A high index of suspicion and regular surveillance is recommended in chronic anorectal fistulas in Crohn's disease. In case of doubt, repeated biopsies should be performed to rule out malignancy.

Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry.

This study aimed to evaluate tumour hypoxia by comparing [(18)F]Fluoromisonidazole uptake measured using positron emission tomography ([(18)F]FMISO-PET) with immunohistochemical (IHC) staining techniques. Syngeneic rhabdomyosarcoma (R1) tumour pieces were transplanted subcutaneously in the flanks of WAG/Rij rats. Tumours were analysed at volumes between 0.9 and 7.3 cm(3). Hypoxic volumes were defined using a 3D region of interest on 2 h postinjection [(18)F]FMISO-PET images, applying different thresholds (1.2-3.0). Monoclonal antibodies to pimonidazole (PIMO) and carbonic anhydrase IX (CA IX), exogenous and endogenous markers of hypoxia, respectively, were used for IHC staining. Marker-positive fractions were microscopically measured for each tumour, and hypoxic volumes were calculated. A heterogeneous distribution of hypoxia was observed both with histology and [(18)F]FMISO autoradiography. A statistically significant correlation (P<0.05) was obtained between the hypoxic volumes defined with [(18)F]FMISO-PET and the volumes derived from the PIMO-stained tumour sections (r=0.9066; P=0.0001), regardless of the selected threshold between 1.4 and 2.2. A similar observation was made with the CA IX staining (r=0.8636; P=0.0006). The relationship found between [(18)F]FMISO-PET and PIMO- and additionally CA IX-derived hypoxic volumes in rat rhabdomyosarcomas indicates the value of the noninvasive imaging method to measure hypoxia in whole tumours.

Relation between different methods for analysing ST segment deviation and infarct size as assessed by positron emission tomography.

OBJECTIVE: To study the relation between resolution of ST segment deviation and infarct size using positron emission tomography. METHODS: 45 patients with ST segment elevation acute myocardial infarction treated with thrombolysis or percutaneous coronary intervention were studied prospectively. An ECG was taken before and at (mean (SD)) 100 (45) min after reperfusion therapy. ECGs were analysed by three methods. Residual ST segment deviation, obtained from the ECG immediately after completion of reperfusion therapy, was defined by summation for each of the three methods. Relative resolution of ST segment deviation was defined as the absolute resolution divided by the ST segment deviation score at baseline x 100 (%). After 29 (14) hours, myocardial blood flow was measured with 13NH3. For each patient, the regions with a myocardial blood flow < 80% of normally perfused myocardium ( = hypoperfusion) and < 50% ( = no reflow) were automatically delineated. RESULTS: Substantial differences were found between different ECG analysis methods. There were moderate correlations between the area with myocardial hypoperfusion and ST segment deviation scores at baseline and after reperfusion therapy. After reperfusion therapy, residual ST segment deviation in the single lead with maximum ST segment deviation was as good at discriminating between tertiles of myocardial damage as summed ST segment elevation. Relative ST segment resolution did not discriminate between different degrees of myocardial damage. CONCLUSIONS: In the individual patient, residual ST segment deviation after reperfusion in the single lead with maximum ST segment deviation is at least as good as summed ST elevation in predicting final myocardial damage.

Position of positron emission tomography and other imaging diagnostic modalities in esophageal cancer.

Positron emission tomography (PET) using the positron emitting glucose analogue 18F-fluorodeoxyglucose (FDG) has emerged as a useful metabolism-based wholebody imaging tool for gastro-esophageal cancer diagnosis and follow up. Most large cancer centers worldwide are now equipped for PET (or even PET-CT). Therefore, there is a growing need for a clear definition of the relative position of PET within the currently available diagnostic modalities. Significant scientific data indicate that FDG-PET adds clinically useful information to the information obtained by standard means (mainly CT and endoscopic ultrasound) throughout the different phases of clinical patient management: 1) at initial diagnosis: PET detects more frequently distant lymph node involvement and organ metastases compared to conventional diagnostics, allowing a more accurate selection of the most appropriate treatment; 2) during chemotherapy: semi-quantitative FDG-PET allows early identification of non-responding patients. Indeed, the metabolic response as measured by serial FDG-PET can be used to predict the clinical and histopathological response. Moreover, the PET-response seems to be related to overall and disease free survival; 3) after a treatment: FDG-PET allows accurate assessment of the residual tumor load; 4) in the follow up: FDG-PET allows accurate detection and restaging of recurrent disease.

Quantifying myocardial deformation throughout the cardiac cycle: a comparison of ultrasound strain rate, grey-scale M-mode and magnetic resonance imaging.

Strain rate imaging (SRI) is a new ultrasound (US) approach to the quantification of regional myocardial deformation. It previously has been validated in vitro and in vivo against other imaging techniques. However, in all such studies, only peak strain values were compared, and the temporal evolution of the strain curve was not studied. Yet, it is the temporal evolution of the strain curves that contains the more important clinical information (e.g., asynchrony, viability, etc). Thus, the aim of this study was to compare the evolution of strain during the complete cardiac cycle as measured by US SRI, US grey-scale M-mode and magnetic resonance imaging (MRI). In 10 healthy volunteers and 20 patients with chronic ischaemic heart disease, radial deformation of the inferolateral segment of the left ventricle was measured by US SRI, US M-mode and MRI. The correspondence of the temporal characteristics of these strain curves were compared by defining an intraclass correlation coefficient (ICC). In healthy volunteers, an overall good agreement (mean ICC: 0.75 and 0.63 for systole and diastole) was found between the different methods. However, in patients with abnormal segmental deformation and low peak strain values, the agreement was less (mean ICC: 0.42 and 0.32), but remained within acceptable limits for clinical decision making. Myocardial deformation measurements using SRI correlated well with MRI and US M-mode measurements throughout the complete cardiac cycle.