Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach.

AIM: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy. METHODS: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks. RESULTS: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence. CONCLUSIONS: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.

Partial volume effect in SPECT & PET imaging and impact on radionuclide dosimetry estimates.

Objectives: The spatial resolution of emission tomographic imaging systems can lead to a significant underestimation in the apparent radioactivity concentration in objects of size comparable to the resolution volume of the system. The aim of this study was to investigate the impact of the partial volume effect (PVE) on clinical imaging in PET and SPECT with current state-of-the-art instrumentation and the implications that this has for radionuclide dosimetry estimates. Methods: Using the IEC Image Quality Phantom we have measured the underestimation in observed uptake in objects of various sizes for both PET and SPECT imaging conditions. Both single pixel measures (i.e., SUVmax) and region of interest mean values were examined over a range of object sizes. We have further examined the impact of the PVE on dosimetry estimates in OLINDA in 177Lu SPECT imaging based on a subject with multiple somatostatin receptor positive paragangliomas in the head and neck. Results: In PET, single pixel estimates of uptake are affected for objects less than approximately 18 mm in minor axis with existing systems. In SPECT imaging with medium energy collimators (e.g., for 177Lu imaging), however, the underestimates are far greater, where single pixel estimates in objects less than 2-3×the resolution volume are significantly impacted. In SPECT, region of interest mean values are underestimated in objects less than 10 cm in diameter. In the clinical case example, the dosimetry measured with SPECT ranged from more than 60% underestimate in the largest lesion (28×22 mm in maximal cross-section; 10.2 cc volume) to >99% underestimate in the smallest lesion (4×5 mm; 0.06 cc). Conclusion: The partial volume effect remains a significant factor when estimating radionuclide uptake in vivo, especially in small volumes. Accurate estimates of absorbed dose from radionuclide therapy will be particularly challenging until robust solutions to correct for the PVE are found.

Practical learning through radiation physics problem solving.

INTRODUCTION: The identification of unknown radionuclides is an authentic practical activity for students that provides the foundations for clinical problem solving, especially in the storage and management of radioactive waste. As different radionuclides have different half-lives, some of which are quite long, the storage of waste material has to accommodate the longest of these. Cross contamination requires a method of identifying the radionuclide samples in a mixed sample to safely and appropriately manage disposal. Similarly, identifying a single unknown sample of a radionuclide allows correct handling and disposal. METHODS: Performing a systematic investigation of the physical properties of unknown radioactive samples is a rich learning opportunity to instil understanding of important physics principles among students in nuclear medicine. RESULTS: This manuscript outlines an investigation developed that would allow students to identify single unknown radionuclides based on physical properties and identify the constituent radionuclides of a mixed sample using some additional mathematical curve stripping. CONCLUSION: The processes and solutions are provided with real data and this practical activity can be replicated by students generating their own data. IMPLICATIONS FOR PRACTICE: This paper provides a template and analysis/interpretation guideline for educators and clinicians to deepen understanding of foundation physics. Enhanced and deeper understanding are a vehicle for improved problem solving in clinical and research practice.

Theranostic SPECT reconstruction for improved resolution: application to radionuclide therapy dosimetry.

BACKGROUND: SPECT-derived dose estimates in tissues of diameter less than 3× system resolution are subject to significant losses due to the limited spatial resolution of the gamma camera. Incorporating resolution modelling (RM) into the SPECT reconstruction has been proposed as a possible solution; however, the images produced are prone to noise amplification and Gibbs artefacts. We propose a novel approach to SPECT reconstruction in a theranostic setting, which we term SPECTRE (single photon emission computed theranostic reconstruction); using a diagnostic PET image, with its superior resolution, to guide the SPECT reconstruction of the therapeutic equivalent. This report demonstrates a proof in principle of this approach. METHODS: We have employed the hybrid kernelised expectation maximisation (HKEM) algorithm implemented in STIR, with the aim of producing SPECT images with PET-equivalent resolution. We demonstrate its application in both a dual 68Ga/177Lu IEC phantom study and a clinical example using 64Cu/67Cu. RESULTS: SPECTRE is shown to produce images comparable in accuracy and recovery to PET with minimal introduction of artefacts and amplification of noise. CONCLUSION: The SPECTRE approach to image reconstruction shows improved quantitative accuracy with a reduction in noise amplification. SPECTRE shows great promise as a method of improving SPECT radioactivity concentrations, directly leading to more accurate dosimetry estimates in small structures and target lesions. Further investigation and optimisation of the algorithm parameters is needed before this reconstruction method can be utilised in a clinical setting.

Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.

Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

Diagnosis of upper limb lymphedema: development of an evidence-based approach.

BACKGROUND: The diagnosis of secondary upper limb lymphedema (LE) is complicated by the lack of an agreed-upon measurement tool and diagnostic threshold. The aim of this study was to determine which of the many commonly used and normatively determined clinical diagnostic thresholds has the best diagnostic accuracy of secondary upper limb LE, when compared to diagnosis by an appropriate reference standard, lymphoscintigraphy. MATERIAL AND METHODS: The arms of women treated for breast cancer with and without a previous diagnosis of LE, as well as healthy controls, were assessed using lymphoscintigraphy, bioimpedance spectroscopy (BIS) and perometry. Dermal backflow score determined from lymphoscintigraphy imaging assessment (reference standard) was compared with diagnosis by both commonly used and normatively determined diagnostic thresholds for volume and circumference measurements as well as BIS. RESULTS: For those with established dermal backflow, all commonly used and normatively determined diagnostic thresholds accurately identified presence of LE compared with lymphoscintigraphy diagnosis. In participants with mild to moderate changes in dermal backflow, only a normatively determined diagnostic threshold, set at two standard deviations above the norm, for arm circumference and full arm BIS were found to have both high sensitivity (81% and 76%, respectively) and specificity (96% and 93%, respectively). For this group, strong, and clinically useful, positive (23 and 10, respectively) and negative likelihood (0.2 and 0.3) ratios were found for both the circumference and bioimpedance diagnostic thresholds. CONCLUSION: For the first time, evidence-based clinical diagnostic thresholds have been established for secondary LE. With mild LE, normatively determined circumference and BIS thresholds are superior to the commonly used thresholds.

Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany.

This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year's meeting "the real work has just started" still holds true.

Combined PET/MR: The Real Work Has Just Started. Summary Report of the Third International Workshop on PET/MR Imaging; February 17-21, 2014, Tübingen, Germany.

This paper summarises the proceedings and discussions at the third annual workshop held in Tübingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".

Risk factors of hypomineralised second primary molars in a group of Iraqi schoolchildren.

AIM: To investigate risk factor/s involved in the development of hypomineralised second primary molars and to relate the location of the affected tooth in the dental arches with the timing of the illness/condition incidence. STUDY DESIGN: A cluster sample of 1,000, Iraqi 7-9 year-old children were invited to have their second primary molars examined for demarcated hypomineralised lesions. METHODS: Mothers of 823 children completed a questionnaire-based interview regarding pregnancy and childhood systemic health history. In the clinical examination, the buccal, occlusal and lingual/palatal surfaces of the second primary molar were evaluated for demarcated hypomineralisation lesions by visual examination. RESULTS: A response rate of 82.3% was obtained. Of the children examined, 53 (6.6%) had hypomineralisation defects in at least one second primary molar and were considered as the hypomineralised second primary molar-affected group. Of the total affected teeth (n=83), maxillary molars were the teeth most frequently affected by hypomineralisation throughout all developmental stages (69.9%). Demarcated opacities were the most prevalent lesion type (71.0%). Ninety-four percent of subjects diagnosed with demarcated defects reported various medical conditions possibly associated with hypomineralisation compared with 44% for their non-affected counterparts. Peri-natal medical conditions (45.3%) were the most frequently reported followed by pre-natal and post-natal conditions (24.5%, 9.4%; respectively). STATISTICS: Ill health during pregnancy, delivery complications, neonatal complications, acute childhood illness, birth weight and duration of breast feeding were significant potential risk factors (p<0.05). The greater the number of health events reported, the higher was the chance of developing the defect. Children who experienced neonatal complications and whose mothers reported pregnancy and birth problems were approximately six times more likely to have the defect than those whose mothers had delivery complications only (80% vs 14.6%) (p<0.001). Also of those children whose mothers did not report delivery complications, but were breastfed for less than six months, of low birth weight and had history of upper respiratory tract infection, the chance of hypomineralised defects was over four times more likely to happen than in those who did not suffer any of these problems (25.8% vs 6.7%) (p<0.01). No statistically significant association was revealed between the time of the illness/condition occurrence and the location of the tooth in the dental arches. CONCLUSIONS: Children with hypomineralised second primary molars had experienced more medical conditions than their unaffected peers particularly during the peri-natal period. No single factor was identified as a potential cause, leaving the aetiology of the defect unclear.

Using an external gating signal to estimate noise in PET with an emphasis on tracer avid tumors.

The purpose of this study is to establish and validate a methodology for estimating the standard deviation of voxels with large activity concentrations within a PET image using replicate imaging that is immediately available for use in the clinic. To do this, ensembles of voxels in the averaged replicate images were compared to the corresponding ensembles in images derived from summed sinograms. In addition, the replicate imaging noise estimate was compared to a noise estimate based on an ensemble of voxels within a region. To make this comparison two phantoms were used. The first phantom was a seven-chamber phantom constructed of 1 liter plastic bottles. Each chamber of this phantom was filled with a different activity concentration relative to the lowest activity concentration with ratios of 1:1, 1:1, 2:1, 2:1, 4:1, 8:1 and 16:1. The second phantom was a GE Well-Counter phantom. These phantoms were imaged and reconstructed on a GE DSTE PET/CT scanner with 2D and 3D reprojection filtered backprojection (FBP), and with 2D- and 3D-ordered subset expectation maximization (OSEM). A series of tests were applied to the resulting images that showed that the region and replicate imaging methods for estimating standard deviation were equivalent for backprojection reconstructions. Furthermore, the noise properties of the FBP algorithms allowed scaling the replicate estimates of the standard deviation by a factor of 1/square root N, where N is the number of replicate images, to obtain the standard deviation of the full data image. This was not the case for OSEM image reconstruction. Due to nonlinearity of the OSEM algorithm, the noise is shown to be both position and activity concentration dependent in such a way that no simple scaling factor can be used to extrapolate noise as a function of counts. The use of the Well-Counter phantom contributed to the development of a heuristic extrapolation of the noise as a function of radius in FBP. In addition, the signal-to-noise ratio for high uptake objects was confirmed to be higher with backprojection image reconstruction methods. These techniques were applied to several patient data sets acquired in either 2D or 3D mode, with (18)F (FLT and FDG). Images of the standard deviation and signal-to-noise ratios were constructed and the standard deviations of the tumors' uptake were determined. Finally, a radial noise extrapolation relationship deduced in this paper was applied to patient data.

Evaluation of the Cockroft-Gault, Jelliffe and Wright formulae in estimating renal function in elderly cancer patients.

BACKGROUND: More elderly patients are being treated with chemotherapy. Reliable and accurate measures of renal function are needed to obtain predictable, safe and effective exposure to renally excreted drugs. The Jelliffe, Cockroft-Gault and Wright formulae have been used to evaluate renal function, although they have not been validated in elderly oncology patients. We performed a retrospective evaluation of these formulae using the [51Cr]-ethylenediamine tetraacetic acid ([51Cr]-EDTA) method of measuring glomerular filtration rate (GFR) as the 'gold standard'. PATIENTS AND METHODS: Inclusion criteria were age > or = 70 years and serum creatinine <250 micromol/l, performed within 4 weeks of glomerular filtration rate (GFR) measurement. Creatinine clearance was calculated using the Cockroft-Gault, Jelliffe and Wright formulae. The precision and accuracy of the three formulae were compared with the gold standard. RESULTS: Two hundred and twenty-five patients were evaluated: median age, 74 years (range 70-89); males, 108; females, 117; median creatinine, 84 micromol/l (range 44-186). Correlation coefficients of the Jelliffe, Cockroft-Gault and Wright formulae were similar. In the specific GFR ranges of 50-70, 70-90 and 90-120 ml/min, the bias [mean percentage error (MPE)] was +8%, -4% and -13%, respectively. The degree of bias was greater with the Cockroft-Gault and Jelliffe formulae across the same range of GFR with the MPE being -15%, -25%, -32% and -12%, -19% and -23%, respectively. All three formulae have reduced precision and greater bias at the extremes of GFR. CONCLUSIONS: The Wright formula is the most accurate, precise and least biased formula for the calculation of GFR in elderly patients with a GFR >50 ml/min. These results allow the physician to make a decision regarding the use of the formula based on an expected degree of bias.

Regional mucociliary clearance in patients with cystic fibrosis.

This paper reports on a large retrospective analysis of mucociliary clearance (MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age-matched healthy subjects. As many of the CF patients were studied on multiple occasions, a total of 184 patient studies are presented. MCC was measured using a radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC was measured from the central, intermediate, peripheral, basal, mid and apical regions of the lung. MCC was markedly decreased in the CF patient group. Not only was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7 +/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid (14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors that may have influenced MCC in both the normal subjects and CF patients. Age, gender, body mass index, patient genotype, penetration index, spontaneous cough, and various lung function parameters were entered into a stepwise multiple regression model, but none of the factors proved to be statistically important in determining MCC. Both intrasubject repeatability and intersubject variability estimates are presented for the patients and normal subjects that had multiple studies. The values were found to be remarkably similar for both CF patients and normal subjects and for both intra- and intersubject repeatability. With marked deviation from normal ranges and good repeatability, the measurement of MCC in CF patients would seem to be a valuable outcome measure for clinical trials involving new pharmaceuticals and physical therapy designed to improve removal of secretions from the airways.

Parametric image reconstruction using spectral analysis of PET projection data.

Spectral analysis is a general modelling approach that enables calculation of parametric images from reconstructed tracer kinetic data independent of an assumed compartmental structure. We investigated the validity of applying spectral analysis directly to projection data motivated by the advantages that: (i) the number of reconstructions is reduced by an order of magnitude and (ii) iterative reconstruction becomes practical which may improve signal-to-noise ratio (SNR). A dynamic software phantom with typical 2-[11C]thymidine kinetics was used to compare projection-based and image-based methods and to assess bias-variance trade-offs using iterative expectation maximization (EM) reconstruction. We found that the two approaches are not exactly equivalent due to properties of the non-negative least-squares algorithm. However, the differences are small (< 5%) and mainly affect parameters related to early and late time points on the impulse response function (K1 and, to a lesser extent, VD). The optimal number of EM iteration was 15-30 with up to a two-fold improvement in SNR over filtered back projection. We conclude that projection-based spectral analysis with EM reconstruction yields accurate parametric images with high SNR and has potential application to a wide range of positron emission tomography ligands.

Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline. METHODS: Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl. RESULTS: There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1. CONCLUSIONS: Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.

ECAT ART - a continuously rotating PET camera: performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department.

Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameterx20 cm long cylindrical phantom, no scatter correction) is 11400 cps.kBq-1.ml-1. This compares with 5800 and 40500 cps.kBq-1.ml-1 in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350-650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of approximately 15 kBq.ml-1 in the cylinder. Spatial resolution is approximately 6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 microSv. h-1 for a typical fluorine-18 fluorodeoxyglucose (18F-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with18F-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging.

The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice.

The MRL lpr/lpr mouse strain is an animal model for the autoimmune disorder systemic lupus erythematosus (SLE). Pathologic changes in the mice include a severe proliferative glomerulonephritis, lymph node and spleen enlargement, increase in autoantibody titers, and shortened life spans. In the present investigation, female MRL lpr/lpr mice have been dosed po daily for 7 months with the selective estrogen receptor modulator (SERM) LY139478 (4 mg/kg) or 17alpha-ethinylestradiol (EE2, 1 mg/kg) and compared to vehicle control animals. The LY139478 group had an increase in survival (73% survival at 7 months, P = 0.02) but the EE2-treated animals did not (53% survival at 7 months, P = 0.4) when compared to the control group (32% survival at 7 months). Although there were no reductions in autoantibody levels as determined by anti-DNA antibody ELISA, histological analysis of kidney tissue indicated that both LY139478 and EE2 mitigated the progression of glomerular nephritis which was evident in the controls. In contrast, there were no significant differences in lymph node size although the LY139478 and EE2 groups retained a well-defined sinusoidal region. Finally, flow cytometric analysis documented that thymuses from animals treated for 7 months with LY139478 but not with EE2 contained predominantly CD4+/CD+ T cells consistent with a normal thymic phenotype observed in non-MRL lpr/lpr mouse strains. These studies demonstrate that SERMs may be potentially useful for the treatment of autoimmune disorders.

Effect of hypertonic saline, amiloride, and cough on mucociliary clearance in patients with cystic fibrosis.

In patients with cystic fibrosis (CF), dehydration of airway secretions leads to a decrease in mucociliary clearance (MCC). We examined the acute effect of MCC of a single administration by aerosolization of hypertonic saline (7%) (HS), amiloride (0.3% in 0.12% NaCl) (AML) and a combination of AML and HS (AML + HS) in 12 patients with CF using a radioaerosol technique. Isotonic saline [0.9%] (IS) was used as a control solution. As both the AML and HS solutions induced cough in some patients, the last nine patients studied also underwent a cough clearance day. This was to eliminate the possible confounding effect of cough on MCC measurement. Patients ranged from 18 to 28 yr (mean +/- SD, 22 +/- 3) with an FEV1 of 27 to 112% predicted (61 +/- 30%). Following deposition of the radioaerosol, baseline clearance was assessed for 30 min. This was followed by a 30-min intervention period. Assessment of post-intervention clearance for a further 30 min was then performed. Comparison of the amount of radioaerosol cleared from the right lung was made at 60 min (%C60) and 90 min (%C90) using repeated measures ANOVA. The percent cleared at 60 and 90 min was significantly increased with HS (%C60 = 26.5%, %C90 = 29.4%) and the combination of AML + HS (%C60 = 23.1%, %C90 = 27.4%) compared with both IS (%C60 = 14.7%, %C90 = 17.5%) and COUGH (%C60 = 18.0%, %C90 = 19.5%), p < 0.01. Inhalation of hypertonic saline is a potentially useful treatment in patients with cystic fibrosis.

Simultaneous emission and transmission measurements for attenuation correction in whole-body PET.

UNLABELLED: We describe a methodology for measuring and correcting for attenuation in whole-body PET using simultaneous emission and transmission (SET) measurements. METHODS: The main components of the methodology are: (a) sinogram windowing of low activity (< or = 50 MBq) rotating 68Ge/Ga rod sources, (b) segmented attenuation correction (SAC) and (c) maximum likelihood reconstruction using the ordered subsets EM (OS-EM) algorithm. The methods were implemented on a whole-body positron emission tomograph. Quantitative accuracy and the signal-to-noise ratio (SNR) were measured for a thorax-tumor phantom as functions of acquisition time (range: 2-20 min per position). RESULTS: When a typical rod source activity (200 MBq 68Ge/Ga) was used, emission SNR was 60% lower in simultaneous than in separate measurements. The difference was only 14% when the rods contained 45 MBq 68Ge/Ga. The SNR was further improved by SAC in conjunction with OS-EM reconstruction and the relative gain increased with increasing acquisition time. Quantitative estimates of tumor, liver and lung radioactivity agreed with values obtained from a separate high count measurement to within 8%, independent of acquisition time. CONCLUSION: Attenuation correction of whole-body PET images is feasible using SET measurements. There is good quantitative agreement with conventional methods and increased noise is offset by the use of SAC and OS-EM reconstruction.