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.

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 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.

Radioisotope section scanning.

Radioisotope section scanning, a relatively new imaging technique, can be regarded as "in vivo autoradiography." It permits, via computer utilization, reconstruction of a three-dimensional image of the distribution of a radioactive tracer within the body. Rapid progress in the design of instrumentation has allowed for initial clinical trials to be carried out. Worldwide, some 30 centers are currently engaged in research in this field, simultaneously ascertaining the physical performance characteristics and figures of merit of the different apparatuses and clarifying the most promising areas of clinical application. This paper is concerned only with radioisotope section scanning via standard radionuclides and radiopharmaceuticals. It does not address itself to work involving positron-emitting radionuclides. Data are given on the physical parameters and areas of clinical application of several types of available equipment.

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Dobutamine thallium myocardial perfusion tomography.

Dobutamine has favorable properties for the pharmacologic manipulation of myocardial oxygen demand in the provocation of ischemia during the investigation of coronary artery disease. The value of dobutamine infusion for thallium myocardial perfusion tomography was assessed in 50 patients with exertional chest pain undergoing coronary arteriography. Dobutamine was infused in 5-min stages at incremental rates from 5 to 20 micrograms/kg per min or until limited by symptoms. The myocardium was divided into nine segments for analysis of perfusion. Thirty-nine of 40 patients with coronary artery disease had a reversible perfusion defect demonstrated by dobutamine thallium tomography (sensitivity 97%) and 8 of 10 patients with normal coronary arteries had normal myocardial perfusion (specificity 80%). These values were significantly better than the sensitivity and specificity of exercise electrocardiography (78% and 44%, respectively; p less than 0.01). There was a significant relation between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6 segments in zero-, one-, two- and three-vessel disease, respectively; p less than 0.001). There was also a significant relation between the maximal tolerated dose of dobutamine and the treadmill exercise time (r = 0.56, p less than 0.001), but a wide range of exercise times was achieved in the 15- and 20-micrograms/kg per min groups, principally because of exercise limitation by noncardiac symptoms. Dobutamine infusion was well tolerated in all patients, including six with asthma. There were no significant arrhythmias or limiting symptoms other than chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct effect of dobutamine on action potential duration in ischemic compared with normal areas in the human ventricle.

BACKGROUND AND OBJECTIVES: The arrhythmogenic effect of beta-adrenoceptor stimulation is complex and may differ in ischemic and normal myocardium. In this study we examined the differential effect of beta-adrenergic stimulation on ventricular action potential duration and, hence, dispersion of repolarization in potentially ischemic versus nonischemic human ventricular myocardium. METHODS: Simultaneous biventricular monophasic action potentials were recorded in 14 patients (28 recording sites) during infusion of dobutamine in incremental doses (low dose 5 micrograms/kg per min, high dose 10 to 15 micrograms/kg per min) during atrial pacing. Perfusion at the action potential recording site was assessed by incorporating myocardial perfusion scintigraphy with injection of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile during the recording at peak doses of dobutamine. Action potential duration during dobutamine infusion was compared with that during atrial pacing to identical rates in the absence of dobutamine. RESULTS: In 21 normal zone recordings, dobutamine produced a variable effect over that produced by atrial pacing to identical heart rates, either lengthening or shortening the action potential duration. The mean (+/- SEM) value for the additional effect of dobutamine was 0.9 +/- 2.5 ms with low doses and -4 +/- 2.6 ms with high doses (p = NS). In seven recordings from potentially ischemic zones, low dose dobutamine had a similar effect (mean change -3.4 +/- 6.5 ms; p = NS vs. normal zone values). However, the high dose dobutamine invariably shortened the action potential duration by a mean of -22.9 +/- 2.9 ms. (p less than 0.05 vs. low dose in ischemic areas, p less than 0.01 vs. normal zone recordings). Pacing alone or the addition of dobutamine had no significant effect on the normal dispersion of action potential duration between two nonischemic recording sites. In recordings in a normal and an abnormally perfused site, high dose dobutamine significantly altered the dispersion of action potential duration. CONCLUSIONS: These results suggest a different effect of beta adrenergic stimulation in potentially ischemic compared with nonischemic human ventricular myocardium. The abnormal dispersion of repolarization thus created may well be important in beta-receptor-mediated arrhythmogenesis during myocardial ischemia.

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.

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.

Striatal dopamine receptor binding in epileptic psychoses.

In order to study the nature of dopaminergic activity in epileptic psychoses we investigated striatal dopamine receptor binding in 14 patients with epilepsy. Seven of the patients were acutely psychotic when studied, having recently developed a periictal schizophreniform psychosis. The remaining patients were not psychotic. All patients were scanned using single photon emission tomography (SPET) with 123I-IBZM, a specific dopamine D2 receptor ligand. A region of interest analysis was performed. Comparison of mean basal ganglia to occipital cortex activity ratios in the two groups demonstrated significantly reduced specific binding of 123I-IBZM to striatal D2 receptors in the psychotic patients compared to those without psychosis.

Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I-iomazenil SPET study.

BACKGROUND: The role of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in schizophrenia has previously been investigated using postmortem material. Recently, using single photon emission tomography (SPET) with the selective benzodiazepine antagonist 123I-Iomazenil as the radioligand, we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia. The present study aimed to build on this using the same in vivo scanning techniques, and relating findings to cognitive functioning. METHODS: Ten nonpsychiatric control subjects and 15 schizophrenic patients, matched for age and handedness, were scanned. A battery of neuropsychologic tests was also administered. RESULTS: Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance, in the schizophrenic group compared to the control group. CONCLUSIONS: Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning, involving memory and visual attention processes, in the schizophrenic group but not in the control group. A role for GABA in the pathophysiology of schizophrenia is suggested. Limitations of the present study and suggestions for future research are discussed.

CBF tomograms with [99mTc-HM-PAO in patients with dementia (Alzheimer type and HIV) and Parkinson's disease--initial results.

We present preliminary data on the utility of functional brain imaging with [99mTc]-d,l-HM-PAO and single photon emission computed tomography (SPECT) in the study of patients with dementia of the Alzheimer type (DAT), HIV-related dementia syndrome, and the "on-off" syndrome of Parkinson's disease. In comparison with a group of age-matched controls, the DAT patients revealed distinctive bilateral temporal and posterior parietal deficits, which correlate with detailed psychometric evaluation. Patients with amnesia as the main symptom (group A) showed bilateral mesial temporal lobe perfusion deficits (p less than 0.02). More severely affected patients (group B) with significant apraxia, aphasia, or agnosia exhibited patterns compatible with bilateral reduced perfusion in the posterior parietal cortex, as well as reduced perfusion to both temporal lobes, different from the patients of the control group (p less than 0.05). SPECT studies of HIV patients with no evidence of intracraneal space occupying pathology showed marked perfusion deficits. Patients with Parkinson's disease and the "on-off" syndrome studied during an "on" phase (under levodopa therapy) and on another occasion after withdrawal of levodopa ("off") demonstrated a significant change in the uptake of [99mTc]-d,l-HM-PAO in the caudate nucleus (lower on "off") and thalamus (higher on "off"). These findings justify the present interest in the functional evaluation of the brain of patients with dementia. [99mTc]-d,l-HM-PAO and regional cerebral blood flow (rCBF)/SPECT appear useful and highlight individual disorders of flow in a variety of neuropsychiatric conditions.

Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia.

OBJECTIVE: Although there is evidence from postmortem studies suggestive of deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) in schizophrenia, no direct in vivo evidence has been obtained to date. The authors used single photon emission computed tomography (SPECT) with iodine-123-labeled iomazenil ([123I]iomazenil), a radioligand that selectively binds with high affinity to the benzodiazepine subunit of the GABAA receptor complex in the human brain, to investigate the presence of benzodiazepine receptor abnormalities in the cerebral cortex of living subjects with schizophrenia. METHOD: Dynamic [123I]iomazenil SPECT was performed in 15 patients (14 patients with DSM-III-R schizophrenia and one with schizophreniform disorder) and 12 healthy subjects over a period of 2 hours. The time-integral method was used to generate ratios of "specific" to "nonspecific" [123I]iomazenil binding at equilibrium for several cortical regions. RESULTS: No overall between-group differences in benzodiazepine receptor binding were found, but significant correlations emerged between the severity of schizophrenic symptoms and [123I]iomazenil binding in limbic cortical regions: positive symptom scores were negatively correlated with benzodiazepine receptor binding in the left medial temporal region, and negative symptoms were inversely related to receptor binding in the medial frontal region. These correlations were not significant when a Bonferroni correction for multiple comparisons was applied. CONCLUSIONS: These preliminary results are consistent with previous research implicating limbic cortical regions in the pathophysiology of schizophrenia, suggesting that reduced inhibitory GABAergic tone in these areas may contribute to the appearance of schizophrenic symptoms.

The role of dynamic imaging in sentinel lymph node biopsy in breast cancer.

The aim of this study was to evaluate the role of dynamic imaging in sentinel lymph node (SLN) biopsy in breast cancer. Patients with T1/T2, N0 invasive breast cancer underwent SLN localisation using intra-dermal injection of 15 MBq of 99mTc-nanocolloid. Gamma camera anterior-oblique dynamic imaging commenced simultaneously with tracer administration for 45 min, and was followed by anterior and lateral static imaging. Dynamic imaging data was reformatted into image files of different time-frames. Patterns of uptake were analysed using the sequences of dynamic frames and time-activity curve (TAC). SLN localisation was successful in 70/73 studies (96%) in 72 patients. Imaging information was present within the first 15 min of dynamic imaging in 67/70 studies (96%). Critical analysis of dynamic data helped to differentiate true SLN from secondary echelon nodes in eight studies and transient foci of radioactivity in six studies. In 17 studies, SLN contained metastatic disease. The detection of SLN metastasis was independent from the use of dynamic imaging. Dynamic imaging improves the interpretation of preoperative SLN imaging for breast cancer, but does not contribute significantly to the successful detection of SLN. Hence, preoperative dynamic imaging is not necessary in SLN biopsy for breast cancer.

Whole-body imaging of thallium-201 after six different stress regimens.

UNLABELLED: There are a number of stress techniques in common use for 201Tl myocardial imaging but few studies have been performed comparing the biodistribution of 201Tl in each case. METHODS: We studied 36 normal patients after six different stress regimens by whole-body imaging, 40 min after 201Tl injection. The stress regimens were exercise, dipyridamole, adenosine or dobutamine alone in standard doses and exercise combined with a vasodilator (dipyridamole or adenosine). RESULTS: Cardiac uptake expressed as a percentage of whole body uptake was greater for the vasodilators compared with exercise (p < 0.005), and this difference was unaffected by combining either vasodilator with exercise. Intermediate results were found with dobutamine. Heart-to-liver (p < 0.01) and abdomen (p < 0.05) ratios were greater for exercise compared with the vasodilators, and this difference was also unaffected by combining the exercise with either vasodilator. Heart-to-lung ratios were highest with any stress involving exercise (p < 0.05). The heart-to-background ratios with dobutamine were similar to the vasodilators. CONCLUSION: Vasodilator infusion yields higher cardiac 201Tl uptake than exercise, but when given alone this results in poor heart-to-background ratios. Combining either vasodilator with exercise maintains the high cardiac uptake, but substantially improves the heart-to-background ratios to levels similar to exercise alone. Dobutamine stress produces an intermediate cardiac uptake, and heart-to-background ratios similar to the vasodilators. Therefore, optimal imaging conditions are obtained by stress which combines a vasodilator with exercise.

Technetium-99m-MDP patterns in patients with painful shoulder lesions.

UNLABELLED: There is no consensus on the optimum mode of imaging in patients with painful shoulder lesions. There is a particular paucity of scintigraphic data. As a result, the strengths and weaknesses of scintigraphy cannot be adequately compared to other imaging techniques used in shoulder imaging. This study evaluated whether specific patterns of scintigraphic abnormality could be detected in patients with painful shoulders seen in rheumatological practice using 99mTc-methylene diphosphonate (MDP). METHODS: Scintigraphic abnormalities were recorded in consecutive patients presenting to a rheumatology clinic with unilateral shoulder pain. Patients were subdivided according to patterns of clinical abnormality consistent with a working diagnosis of a lesion located in the subacromial region, adhesive capsulitis (frozen shoulder) or a lesion likely to be located in the glenohumeral joint. Patterns of radiopharmaceutical distribution in different regions of the shoulder were evaluated in the light of clinical data and the results of shoulder radiographs. RESULTS: Technetium-99m-MDP scans were abnormal in 19 of 24 (79%) patients, and radiographs were abnormal in 8 of 24 (33%) patients. Distinct patterns of 99mTc-MDP image abnormality were identified: an increase in 99mTc-MDP uptake in the coracoid, acromion and medial humeral head on anterior planar images, together with an absence of posterior planar image abnormality, frequently occurred in association with a working diagnosis of a lesion located in the subacromial region. Posterior planar 99mTc-MDP image abnormalities always occurred in patients with clinical features consistent with a diagnosis of adhesive capsulitis. There was an 85% agreement between two observers' scores when 99mTc-MDP distribution in specific shoulder regions was graded. CONCLUSION: Distinct patterns of 99mTc-MDP distribution may be associated with clinically-distinct patterns of abnormality in patients with painful shoulder lesions. Further studies to elucidate a role for 99mTc-MDP scintigraphy in this patient group are warranted.

Samarium-153-particulate hydroxyapatite radiation synovectomy: biodistribution data for chronic knee synovitis.

UNLABELLED: Biodistribution data for the radiation synovectomy agent samarium-153-particulate hydroxyapatite (153Sm-PHYP) are reported. METHODS: Mean extra-articular activity accumulation calculated from serial whole-body scans in 13 patients treated for chronic knee synovitis was 0.74% of injected activity (range 0%-3%). RESULTS: In four patients (31%), activity was noted in the lung (mean 0.68% of injected activity). In six patients (46%), 0.29% of injected activity accumulated in the regional lymph nodes and in three patients (23%), 0.62% of injected dose accumulated in the liver. Absorbed dose estimates were lung: 14 mGy, regional lymph nodes; 50 mGy, liver; 4 mGy. SPECT demonstrated good distribution of 153Sm-PHYP throughout the anterior knee compartments, although distribution to the posterior compartment was variable. CONCLUSION: Distribution is dependent on adequate knee flexion immediately following injection and may be influenced by the size range of labeled particles. Favorable biodistribution data suggest that 153Sm-PHYP is a potentially useful radiation synovectomy agent.

Contrast nephrotoxicity and the role of radionuclide renal scan.

Radiographic contrast media-induced nephrotoxicity is an important cause of acute renal failure. The indications of using contrast are usually unavoidable, compelling and continue to expand, especially in the vascular field. When acute renal failure follows such a procedure, it becomes important to establish the presence of contrast nephrotoxicity or an acute occlusive event which may have precipitated the failure. We present two cases of contrast nephrotoxicity in patients with impaired renal function. Radionuclide renal studies with 99mTc-DTPA (Patient 1) and 99mTc-MAG3 (Patient 2), confirmed the presence of acute tubular necrosis and excluded major occlusive vascular events. Renal scintigraphy remains an important but underused test which can rule out obvious renal vascular occlusion and/or support the diagnosis of contrast-related acute tubular necrosis, as the cause of renal failure in these patients.

A new transverse-section brain imager for single-gamma emitters.

Physical and clinical data on a new emission transverse-section scanner are given. Comparative data from an earlier tomoscanner and a rotating gamma-camera system yield the following information for the three imagers. Resolution at the center of the field is 9 mm for this tomoscanner, 18 mm for the earlier tomoscanner, and 11 mm for the rotating camera; sensitivity (cps/muCi-ml) 36K, 15.4K, 1.9K; crystal area (cm2) 3096, 619, 490, respectively. The quantification of images is discussed. Clinical emission section scans of the brain, liver, chest and skull are presented and discussed. Forty brain scans were analyzed in conjunction with x-ray transmission tomography. No false positives were found. From a total of 15 lesions seen by the CT x-ray scanner, 14 were detected by the emission tomographic scanner, 12 by standard gamma-camera imaging. One false negative case (cyst) was seen by the transmission x-ray scanner but not by the emission scanner.