The role of ¹8fluoro-deoxy glucose combined position emission and computed tomography in the clinical management of anal squamous cell carcinoma.

AIM: Anal squamous cell carcinoma (SCC) is uncommon in the western world but continues to increase in incidence. Optimal treatment and outcome are dependent upon pretreatment staging strategies. We evaluate the role of ¹8fluoro-deoxyglucose (¹8FDG) combined position emission and computed tomography (PETCT) in the management of anal SCC. METHOD: Patients with a histologically confirmed anal SCC underwent standard staging investigations, including computed tomography, Magnetic resonance imaging and examination under anaesthetic. A tumour, node, metastasis (TNM) system was used. All patients subsequently underwent additional whole-body ¹8FDG PETCT scanning. Management was planned accordingly, blinded to ¹8FDG PETCT findings, at a multidisciplinary meeting, and reviewed again following disclosure of PETCT results. RESULTS: Forty patients (24 men), with a median age of 57 years (range 38-87 years), were prospectively recruited. All primary tumours were ¹8FDG avid. PETCT did not alter the T stage but did result in disease upstaging (N and M stages). Management was altered in five (12.5%) patients: one patient was identified to have an isolated distant metastasis, and four patients had ¹8FDG-avid lymph nodes not otherwise detected, all of which were tumour-positive on fine needle aspiration cytology/biopsy. CONCLUSION: PETCT upstages anal SCC and influences subsequent management. PETCT should be considered in the staging of anal SCC, although the definitive benefit of such a strategy requires further evaluation.

Sentinel node imaging in breast cancer using superficial injections: technical details and observations.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is the evolving standard of care for the management of early breast cancer. Accurate identification of the SLN is paramount for success of this procedure. Various techniques are described for SLN identification, but the superficial injection techniques, advocated by the UK National Training Programme (NEW START), are validated, reproducible and rapid. Pre-operative lymphoscintigraphy provides a road map for the surgeon and requires a reporting template. METHODS: As one of the NEW START training institutions in the UK practising this technique, we reviewed a mature series of 100 unselected, consecutive SLN lymphoscintigraphy procedures. We correlated the imaging, operative and pathology findings and have provided technical details of the technique and a template for reporting SLN lymphoscintigrams. RESULTS: The SLN localisation rate was 99% with one failed imaging. Seven patients required delayed imaging. The mean activity of the radiocolloid injected was 14.4MBq (range 8.3-23 MBq). The SLNs were visualised in the ipsilateral axilla in 98 images, intramammary in 3, and internal mammary in 1. A mean of 1.35 nodes were classified as 'True' SLNs on imaging criteria. Intra-operatively, a mean of 1.91 SLNs were excised. 32 of 116 hot and blue nodes, 7 of 15 only blue nodes, 13 of 47 only hot and 7 of 13 parasentinel nodes harboured metastases. CONCLUSION: The NEW START recommended, combined superficial injection techniques, have high localisation rates. Pre-operative sentinel node imaging is recommended and a template for reporting is provided.

Increased metabolic activity in abdominal aortic aneurysm detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT).

OBJECTIVES: Abdominal aortic aneurysms (AAAs) are associated with an inflammatory cell infiltrate and enzymatic degradation of the vessel wall. The aim of this study was to detect increased metabolic activity in the wall of the AAA with 18F-fluorodeoxyglucose ((18)F-FDG), mediated by glucose transporter protein (GLUTs), using a dedicated hybrid PET/64-detector CT. DESIGN, METHOD AND MATERIALS: 14 patients (All male, mean age 73.6 years, range 61-82) with AAA under surveillance underwent PET/CT scanning with 175 MBq of intravenous (18)F-FDG. The maximum aneurysm diameter and calcification score were determined on the attenuation correction CT. A volume of interest was placed on the aneurysm sac and the maximum Standardised Uptake Value (SUV(max)) measured. RESULTS: The mean aneurysm diameter was 5.4 cm (SD+/-0.8). Two aneurysms had the CT characteristics of inflammatory aneurysms. Twelve aneurysms showed increased FDG uptake (SUV(max)>2.5). There was no significant difference in FDG uptake between heavily calcified aneurysms and non-heavily calcified aneurysms (t-test). There was a significant increase in the FDG uptake in the two inflammatory aneurysms compared to the other twelve aneurysms (t-test; P=0.04). CONCLUSION: The findings in this study offer in vivo evidence that the AAA wall shows increased glucose metabolism, mediated by the GLUTs: this increased metabolic activity as detected by PET/CT may be present in most AAAs.

The incremental value of dual modality PET/CT imaging over PET imaging alone in advanced colorectal cancer.

BACKGROUND: (18)Fluoro-2-Deoxy Glucose (18 FDG) positron emission tomography (PET) impacts upon the management of recurrent colorectal cancer (CRC) but is limited by anatomical localisation. The development of integrated positron emission and computerised tomography (PET/CT) yields high anatomical resolution combined with the PET data. We evaluate the added value of PET/CT over PET alone. METHOD: Thirty-one consecutive patients had PET/CT for suspected recurrent CRC. Two blinded observers (A and B) reported images from PET alone and from integrated PET/CT. Lesion detection, lesion localisation, diagnostic certainty and impact on surgical management was assessed for each data set and then compared. The minimum clinical follow up was for 8 months (median 9.6 months) and 7 patients had histological confirmation of diagnosis. RESULTS: Compared to PET alone, PET/CT the percentage of lesions accurately localised increased from 96% to 99% for observer A and 86% to 99% for Observer B. PET/CT increased the number of lesions reported as definitely abnormal or normal from 78% to 95% for Observer A and from 72% to 94% for Observer B. Surgical management was changed in 6 patients (19%). Inter-observer variability was reduced with PET/CT. CONCLUSION: PET/CT improves the accuracy of reporting in recurrent colorectal cancer and influences surgical management in a significant proportion of patients when compared to PET only imaging.

Long-term estrogen therapy and 5-HT(2A) receptor binding in postmenopausal women; a single photon emission tomography (SPET) study.

Variation in estrogen level is reported by some to affect brain maturation and memory. The neurobiological basis for this may include modulation of the serotonergic system. No neuroimaging studies have directly examined the effect of extended estrogen therapy (ET), on the 5-HT(2A) receptor in human brain. We investigated the effect of long-term ET on cortical 5-HT(2A) receptor availability in postmenopausal women. In a cross-sectional study, we compared cortical 5-HT(2A) receptor availability in 17 postmenopausal ERT-naive women and 17 long-term oophorectomised estrogen-users, age- and IQ-matched using single photon emission tomography and the selective 5-HT(2A) receptor ligand (123)I-5-I-R91150. Also, we used the Revised Wechsler Memory Scale to relate memory function to 5-HT(2A) receptor availability. Never-users had significantly higher 5-HT(2A) receptor availability than estrogen-users in hippocampus (1.17 vs. 1.11, respectively, p=0.02), although this did not remain significant after correction for multiple comparisons. Hippocampal 5-HT(2A) receptor availability correlated negatively with verbal and general memory and delayed recall (r=-0.45, p=0.01; r=-0.40, p=0.02; r=-0.36, p=0.04). Right superior temporal 5-HT(2A) receptor availability correlated negatively with verbal memory (r=-0.36, p=0.04). In estrogen-users, receptor availability correlated negatively with verbal and general memory (r=-0.70, p=0.002; r=-0.69, p=0.002); and in never-users, receptor availability negatively correlated with attention and concentration (r=-0.54, p=0.02). Long-term ET may be associated with lower 5-HT(2A) receptor availability in hippocampus. This may reflect increased activity within the serotonergic pathway leading to down-regulation of post-synaptic receptor. Also, increased availability of the 5-HT(2A) receptor in hippocampus is associated with poorer memory function.

99mTechnetium-mercaptoacetyltriglycine scintigraphy with full bladder in patients with severe bladder dysfunction.

PURPOSE: We evaluated 99mtechnetium-mercaptoacetyltriglycine scintigraphy for detecting threshold bladder volume at which upper tract obstruction occurs in patients with bladder dysfunction. MATERIALS AND METHODS: A total of 24 patients 19 to 74 years old with severe bladder dysfunction who underwent 99mtechnetium-mercaptoacetyltriglycine scintigraphy and videocystometrogram in a 4-year period were selected for retrospective study. 99mTechnetium-mercaptoacetyltriglycine scintigraphy was done with a full bladder with a mean instilled volume of more than 850 ml saline. In patients in whom an obstructed renal outflow pattern was observed saline was drained at a rate of 100 ml every 5 minutes while dynamic imaging was performed. If results were abnormal, the study was repeated with an empty bladder. Differential function, parenchymal transit time index and outflow efficiency were calculated. RESULTS: Of the 24 patients 15 had an obstructed outflow pattern with a full bladder, which was relieved at a bladder volume of less than 390 ml (median 300, range 250 to 600). Only 2 of these 15 patients had a normal vesical end filling pressure of less than 20 cm H2O. There was no obstruction in 9 patients, of whom 5 had increased vesical end filling pressures. Followup in patients who had normal tracer outflow on a full bladder showed no decrease in renal function, while a small decrease was seen in patients who had obstructed outflow on a full bladder. CONCLUSION: This novel, full bladder 99mtechnetium-mercaptoacetyltriglycine scintigraphic technique provides the ability to detect bladder volumes at which obstructive outflow patterns develop in patients with severe bladder dysfunction.

The contribution of PET/CT to improved patient management.

With the introduction of both SPET/CT and PET/CT, multimodality imaging has truly entered routine clinical practice. Multiple slice spiral CT scanners have been incorporated with multiple detector gamma cameras or PET systems, such that the benefit of these modalities can be achieved in one patient sitting. The subject of this manuscript is PET/CT and its impact on patient management. Applications of PET/CT span the whole field of medical and surgical oncology since very few cancers do not take up the labelled glucose tracer, (18)F-FDG. Given the contrast achieved, high-quality data can be obtained with FDG PET/CT. This technology has now spread worldwide and has been the subject of intense interest, as witnessed by the vast body of published evidence. In this short overview, only a brief discussion of the main clinical applications is possible. Novel applications of PET/CT outside the field of oncology are expected in the near future.

Clinical evaluation of 2D versus 3D whole-body PET image quality using a dedicated BGO PET scanner.

PURPOSE: Three-dimensional positron emission tomography (3D PET) results in higher system sensitivity, with an associated increase in the detection of scatter and random coincidences. The objective of this work was to compare, from a clinical perspective, 3D and two-dimensional (2D) acquisitions in terms of whole-body (WB) PET image quality with a dedicated BGO PET system. METHODS: 2D and 3D WB emission acquisitions were carried out in 70 patients. Variable acquisition parameters in terms of time of emission acquisition per axial field of view (aFOV) and slice overlap between sequential aFOVs were used during the 3D acquisitions. 3D and 2D images were reconstructed using FORE+WLS and OSEM respectively. Scatter correction was performed by convolution subtraction and a model-based scatter correction in 2D and 3D respectively. All WB images were attenuation corrected using segmented transmission scans. Images were blindly assessed by three observers for the presence of artefacts, confidence in lesion detection and overall image quality using a scoring system. RESULTS: Statistically significant differences between 2D and 3D image quality were only obtained for 3D emission acquisitions of 3 min. No statistically significant differences were observed for image artefacts or lesion detectability scores. Image quality correlated significantly with patient weight for both modes of operation. Finally, no differences were seen in image artefact scores for the different axial slice overlaps considered, suggesting the use of five slice overlaps in 3D WB acquisitions. CONCLUSION: 3D WB imaging using a dedicated BGO-based PET scanner offers similar image quality to that obtained in 2D considering similar overall times of acquisitions.

Use of 18F-FDG positron emission tomography following allogeneic transplantation to guide adoptive immunotherapy with donor lymphocyte infusions.

Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) provides valuable prognostic information in the management of lymphoma patients. However, the utility of (18)F-FDG PET following allografting is unclear. We analysed the use of (18)F-FDG PET after allogeneic reduced-intensity transplantation (RIT) performed in our institution. Between June 1998 and January 2002, 55 patients underwent RIT for either Hodgkin or non-Hodgkin lymphoma. At least one (18)F-FDG PET scan was performed during the post-transplant period (median five studies) in 15 (27.2%) of these 55 patients. PET scans were performed after re-staging computed tomography (CT) and were categorised depending on (18)F-FDG uptake. The first PET scan was informative in 11 of 15 patients (73%) and influenced the administration of donor lymphocyte infusions (DLI) in nine: leading to earlier DLI administration in two patients, earlier dose escalation in one, withholding of DLI administration in five and dose reduction in one. In addition, subsequent monitoring with (18)F-FDG PET scans documented a graft-versus-lymphoma effect in five patients (median post-DLI follow-up 33 months, range 13-36 months). These preliminary data suggest that (18)F-FDG PET has a role in guiding DLI administration and monitoring the immunotherapeutic effect in patients after allogeneic transplantation. This retrospective pilot study forms the basis for a prospective study to clarify the utility of (18)F-FDG PET/CT in these patients.

In vivo imaging of muscarinic receptors in the aging female brain with (R,R)[123I]-I-QNB and single photon emission tomography.

The effect of age on brain muscarinic receptor density is unclear. Some in vivo neuroimaging studies have reported a large age-related reduction in muscarinic receptor density; however, others have reported increases or no change. The variability in these results most likely arises because of the heterogeneity of the populations studied, differences in quantification methods employed, and a paucity of subtype selective ligands. Thus, we used the m(1)/m(4) selective probe (R,R)[(123)I]-I-QNB to investigate age-related differences in brain muscarinic receptors in healthy females. We included 10 younger subjects (age range 26-37) and 22 older women (age range 57-82 years). The older women had significantly lower (R,R)[(123)I]-I-QNB binding in widespread brain regions including cerebral cortex and hippocampus. Across all subjects, regional binding was significantly negatively correlated with age. Thus, in this population of healthy women, there was an age-related reduction in muscarinic receptor density. This may contribute to age-related differences in cognitive function and risk for Alzheimer's disease.

Impact of combined (18)F-FDG PET/CT in head and neck tumours.

To compare the interobserver agreement and degree of confidence in anatomical localisation of lesions using 2-[fluorine-18]fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and (18)F-FDG PET alone in patients with head and neck tumours. A prospective study of 24 patients (16 male, eight female, median age 59 years) with head and neck tumours was undertaken. (18)F-FDG PET/CT was performed for staging purposes. 2D images were acquired over the head and neck area using a GE Discovery LS PET/CT scanner. (18)F-FDG PET images were interpreted by three independent observers. The observers were asked to localise abnormal (18)F-FDG activity to an anatomical territory and score the degree of confidence in localisation on a scale from 1 to 3 (1=exact region unknown; 2=probable; 3=definite). For all (18)F-FDG-avid lesions, standardised uptake values (SUVs) were also calculated. After 3 weeks, the same exercise was carried out using (18)F-FDG PET/CT images, where CT and fused volume data were made available to observers. The degree of interobserver agreement was measured in both instances. A total of six primary lesions with abnormal (18)F-FDG uptake (SUV range 7.2-22) were identified on (18)F-FDG PET alone and on (18)F-FDG PET/CT. In all, 15 nonprimary tumour sites were identified with (18)F-FDG PET only (SUV range 4.5-11.7), while 17 were identified on (18)F-FDG PET/CT. Using (18)F-FDG PET only, correct localisation was documented in three of six primary lesions, while (18)F-FDG PET/CT correctly identified all primary sites. In nonprimary tumour sites, (18)F-FDG PET/CT improved the degree of confidence in anatomical localisation by 51%. Interobserver agreement in assigning primary and nonprimary lesions to anatomical territories was moderate using (18)F-FDG PET alone (kappa coefficients of 0.45 and 0.54, respectively), but almost perfect with (18)F-FDG PET/CT (kappa coefficients of 0.90 and 0.93, respectively). We conclude that (18)F-FDG PET/CT significantly increases interobserver agreement and confidence in disease localisation of (18)F-FDG-avid lesions in patients with head and neck cancers.

A training simulator for sentinel node biopsy in breast cancer: a new standard.

BACKGROUND: Sentinel node biopsy is becoming the staging investigation of choice for early breast cancer. Optimal identification of the sentinel node requires the utilization of a radionuclide in combination with blue dye. Gamma probe guided surgery is a skill that is currently unfamiliar to many surgeons. Appropriate training within the surgical skills laboratory could play a major role in the widespread implementation of this technique, but no suitable model currently exists for this purpose. AIM: To develop a realistic phantom for the teaching and practice of the core new skills required of a surgeon to perform gamma probe guided sentinel node biopsy in breast cancer. METHODS: We describe the development of our sentinel node biopsy simulator which consists of a torso with its arm extended in an operating position. The replaceable breast and axilla are constructed from a thermoplastic elastomer gel, which has similar physical and radiation attenuation properties to that of human tissue. Radionuclide injection sites and radioactive sentinel nodes are simulated by hollow blue coloured PVC beads filled with Technetium-99m. The model allows demonstration and practice of injection techniques, imaging techniques and gamma probe guided removal of sentinel nodes. CONCLUSION: We believe that training for sentinel node biopsy should begin in the surgical skills laboratory. The model we have developed is able to provide an accurate simulation of all new practical skills required for accurate sentinel node identification. It is an important aid to training in the sentinel lymph node biopsy procedure for breast carcinoma.

SPET imaging of central muscarinic receptors with (R,R)[123I]-I-QNB: methodological considerations.

Investigations on the effect of normal healthy ageing on the muscarinic system have shown conflicting results. Also, in vivo determination of muscarinic receptor binding has been hampered by a lack of subtype selective ligands and differences in methods used for quantification of receptor densities. Recent in vitro and in vivo work with the muscarinic antagonist (R,R)-I-QNB indicates this ligand has selectivity for m(1) and m(4) muscarinic receptor subtypes. Therefore, we used (R,R)[(123)I]-I-QNB and single photon emission tomography to study brain m(1) and m(4) muscarinic receptors in 25 healthy female subjects (11 younger subjects, age range 26-32 years and 14 older subjects, age range 57-82 years). Our aims were to ascertain the viability of tracer administration and imaging within the same day, and to evaluate whether normalization to whole brain, compared to normalization to cerebellum, could alter the clinical interpretation of results. Images were analyzed using the simplified reference tissue model and by two ratio methods: normalization to whole brain and normalization to cerebellum. Significant correlations were observed between kinetic analysis and normalization to cerebellum, but not to whole brain. Both the kinetic analysis and normalization to cerebellum showed age-related reductions in muscarinic binding in frontal, orbitofrontal, and parietal regions. Normalization to whole brain, however, failed to detect age-related changes in any region. Here we show that, for this radiotracer, normalizing to a region of negligible specific binding (cerebellum) significantly improves sensitivity when compared to global normalization.

Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer.

Fluorine-18 3'-deoxy-3'-fluorothymidine (18FLT) is a tissue proliferation marker which has been suggested as a new tumour-specific imaging tracer in positron emission tomography (PET). The objectives of this study were to investigate the pharmacokinetics of 18FLT in patients with colorectal cancer, defining methodologies for the quantitative analysis of the in vivo 18FLT uptake and subsequently assessing the accuracy of semi-quantitative measures. Dynamic acquisitions over a single field of view of interest identified by computed tomography were carried out for up to 60 min following injection of 18FLT (360 +/- 25 MBq). Dynamic arterial blood sampling was carried out in order to provide a blood input function. Simultaneous venous samples were also taken in order to investigate their potential utilisation in deriving a hybrid input function. Arterial and venous blood samples at 5, 15, 30, 60 and 90 min p.i. were used for metabolite analysis. Eleven patients with primary and/or metastatic colorectal cancer were studied on a lesion by lesion basis (n = 21). All acquired images were reconstructed using ordered subsets expectation maximisation and segmented attenuation correction. Time-activity curves were derived by image region of interest (ROI) analysis and image-based input functions were obtained using abdominal or thoracic aorta ROIs. Standardised uptake values (SUVs) were calculated to provide semi-quantitative indices of uptake, while non-linear regression (NLR) methodology in association with a three-compartment model and Patlak analysis were carried out to derive the net influx constant Ki. The metabolite analysis revealed two radioactive metabolites, with the parent compound representing approximately 80% of the total radioactivity in the 30-min plasma sample. In the case of NLR, better fits were obtained with a 3k model (i.e. k4 = 0) for both lesion and bone marrow time-activity curves. For the same lesions, a high correlation was observed between the Ki derived from either Patlak analysis or NLR(3k) and the corresponding SUVs. Our results also suggest that the quantitative behaviour of 18FLT in vivo (up to 60 min p.i.) may be characterised using a 3k model or Patlak analysis in combination with image-derived input functions. The good correlation found between the SUVs (at 60 min) and Ki values supports the use of semi-quantitative indices to assess the proliferation rate of colorectal cancer lesions in vivo with 18FLT.

Myocardial perfusion scintigraphy: the evidence.

This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by comparison with the numbers of revascularisations and coronary angiograms performed. Furthermore, MPS activity levels in this country fall far short of those in comparable European countries, with about half as many scans being undertaken per year. Currently, the number of MPS studies performed annually in the UK is 1,200/million population/year. We estimate the real need to be 4,000/million/year. The current average waiting time is 20 weeks and we recommend that clinically appropriate upper limits of waiting time are 6 weeks for routine studies and 1 week for urgent studies.