Quantitative validation of Monte Carlo SPECT simulation: application to a Mediso AnyScan GATE simulation.

BACKGROUND: Monte Carlo (MC) simulations are used in nuclear medicine imaging as they provide unparalleled insight into processes that are not directly experimentally measurable, such as scatter and attenuation in an acquisition. Whilst MC is often used to provide a 'ground-truth', this is only the case if the simulation is fully validated against experimental data. This work presents a quantitative validation for a MC simulation of a single-photon emission computed tomography (SPECT) system. METHODS: An MC simulation model of the Mediso AnyScan SCP SPECT system installed at the UK National Physical Laboratory was developed in the GATE (Geant4 Application for Tomographic Emission) toolkit. Components of the detector head and two collimator configurations were modelled according to technical specifications and physical measurements. Experimental detection efficiency measurements were collected for a range of energies, permitting an energy-dependent intrinsic camera efficiency correction function to be determined and applied to the simulation on an event-by-event basis. Experimental data were collected in a range of geometries with [Formula: see text]Tc for comparison to simulation. The procedure was then repeated with [Formula: see text]Lu to determine how the validation extended to another isotope and set of collimators. RESULTS: The simulation's spatial resolution, sensitivity, energy spectra and the projection images were compared with experimental measurements. The simulation and experimental uncertainties were determined and propagated to all calculations, permitting the quantitative agreement between simulated and experimental SPECT acquisitions to be determined. Statistical agreement was seen in sinograms and projection images of both [Formula: see text]Tc and [Formula: see text]Lu data. Average simulated and experimental sensitivity ratios of ([Formula: see text]) were seen for emission and scatter windows of [Formula: see text]Tc, and ([Formula: see text]) and ([Formula: see text]) for the 113 and 208 keV emissions of [Formula: see text]Lu, respectively. CONCLUSIONS: MC simulations will always be an approximation of a physical system and the level of agreement should be assessed. A validation method is presented to quantify the level of agreement between a simulation model and a physical SPECT system.

EFOMP's protocol quality controls in PET/CT and PET/MR.

This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks.

Guidance on medical physics expert support for nuclear medicine.

The Ionising Radiation (Medical Exposure) Regulations require employers to appoint suitable medical physics experts (MPE) for nuclear medicine services, and they also define the areas where MPEs are required to provide advice and specify matters that they must contribute towards. Applications for employer licences under IR(ME)R require employers to specify the level of MPE support available and if this is provided by onsite MPEs or remotely. Assessment of these applications by the Administration of Radioactive Substances Advisory Committee (ARSAC) has highlighted variability in the levels of MPE support being provided for similar services across the UK. A working party including representatives from IPEM, ARSAC, BIR and BNMS was formed and has produced these recommendations on MPE support. Nuclear medicine services were divided into seven broad categories and MPE support for each category has been considered. However, some services that differ from the scenarios provided in this guidance may require different levels of MPE support. Positron emission tomography (PET)/CT and gamma camera imaging have been considered separately here, although it is recognised that both PET/CT and gamma cameras are often sited within the same department in many centres. The separation has been done for pragmatic purposes, as there are felt to be sufficient differences in the MPE role requirements. This guidance sets out recommendations for MPE support, and broader physics support, to run a safe nuclear medicine service and defines the responsibilities of these staff for a range of clinical nuclear medicine services. The recommendations on MPE support made are advice, but will assist employers in meeting regulatory requirements.

Radioguided Surgery for Gastroenteropancreatic Neuroendocrine Tumours: a Systematic Literature Review.

BACKGROUND: Radioguided surgery (RGS) for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has been suggested as a way to improve intraoperative lesion detection. This systematic literature review of reports of the use of RGS for GEP-NETs was performed to determine if there is a benefit. METHODS: A literature search was conducted using Google Scholar and PubMed, and snowballing from any relevant literature. Full-text studies were included if they were published in the English language and reported outcomes of RGS on human subjects with GEP-NETs. Qualitative data synthesis was performed. RESULTS: Twenty-six papers including a total of 209 patients were included. The tracers used were predominantly indium-111 pentetreotide, gallium-68 DOTA-peptides, and technetium-99m EDDA/HYNIC-peptides. Heterogeneous protocols make comparisons difficult, but most papers reported a benefit from the use of RGS in tumours in the gastrointestinal tract; utility in localisation of pancreatic tumours was less clear. Time between tracer administration and operation varied: from 16 h to 8 days with indium-111, 0-24 h with technetium-99m, and 19-193 min with gallium-68. Eight teams reported the thresholding technique used for discrimination-four used a ratio, four statistical methods, and one looked at the sensitivity and specificity of different cut-offs. Six teams performed follow-up of 24 patients (three pancreas, eight gastrinoma, 13 gastrointestinal tract) for between 3 months and 3 years. Two patients relapsed (one pancreas, one gastrinoma) between 6 and 12 months post-surgery. CONCLUSIONS: RGS appears to aid in localisation of gastrointestinal NETs, but the benefit is more equivocal in pancreatic NETs. Further work into outcomes is warranted.

Safety, tolerability and clinical implementation of 'ready-to-use' 68gallium-DOTA0-Tyr3-octreotide (68Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

BACKGROUND: 68Ga-DOTA0-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography-CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT-CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation of 68Ga-DOTATOC using a new 'ready-to-use' 68Ga-DOTATOC formulation for injection has been developed (68Ga-DOTATOC (SomaKIT TOC)). OBJECTIVES: This study aimed to assess the safety and tolerability of 68Ga-DOTATOC (SomaKIT TOC) and evaluate the feasibility and robustness of implementing it in a NET clinical imaging service. METHODS: A first-in-human phase I/II multicentre, open-label study of a single dose of 68Ga-DOTATOC (SomaKIT TOC) 2 MBq/kg±10% (range 100-200 MBq) in patients with biopsy-proven grade 1-2 GEP-NETs. PET-CT was performed post injection. Patients were followed up for 28 days. We next implemented this new synthesis methodology in a clinical service assessed over 11 months. RESULTS: Twenty consenting patients were recruited; 14 males, 6 females; mean (SD) age 58 years (12); NET grade 1 (70%), grade 2 (30%); and 75% with stage IV disease. Twelve patients experienced at least one adverse event (AE) during the study with no grade 3-4 toxicities. Only four AEs were classified as possibly (headache (n=1; 4%), nausea (1; 4%)) or probably (dysgeusia (1; 4%), paraesthesia (1; 4%)) related to the study preparation. One hundred thirteen vials of 68Ga-DOTATOC (SomaKIT TOC) were synthesised with the 'kit' over a period of 11 months for clinical utility. Only 2/113 vials (1.77%) were rejected. CONCLUSIONS: The new ready-to-use preparation of 68Ga-DOTATOC (SomaKIT TOC) for injection was safe and well tolerated. This has led to the world's first (EMA) licensed 68Ga-DOTATOC (SomaKIT TOC) radiopharmaceutical for the utility of PET imaging in patients with NETs. This preparation can be robustly implemented into routine clinical practice.

[18F]fluorothymidine and [18F]fluorodeoxyglucose PET Imaging Demonstrates Uptake and Differentiates Growth in Neurofibromatosis 2 Related Vestibular Schwannoma.

OBJECTIVE: To investigate whether [F]fluorothymidine (FLT) and/or [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) can differentiate growth in neurofibromatosis 2 (NF2) related vestibular schwannomas (VS) and to evaluate the importance of PET scanner spatial resolution on measured tumor uptake. METHODS: Six NF2 patients with 11 VS (4 rapidly growing, 7 indolent), were scanned with FLT and FDG using a high-resolution research tomograph (HRRT, Siemens) and a Siemens Biograph TrueV PET-CT, with and without resolution modeling image reconstruction. Mean, maximum, and peak standardised uptake values (SUV) for each tumor were derived and the intertumor correlation between FDG and FLT uptake was compared. The ability of FDG and FLT SUV values to discriminate between rapidly growing and slow growing (indolent) tumors was assessed using receiver operator characteristic (ROC) analysis. RESULTS: Tumor uptake was seen with both tracers, using both scanners, with and without resolution modeling. FDG and FLT uptake was correlated (R = 0.67-0.86, p < 0.01) and rapidly growing tumors displayed significantly higher uptake (SUVmean and SUVpeak) of both tracers (p < 0.05, one tailed t test). All of the PET analyses performed demonstrated better discriminatory power (AUCROC range = 0.71-0.86) than tumor size alone (AUCROC = 0.61). The use of standard resolution scanner with standard reconstruction did not result in a notable deterioration of discrimination accuracy. CONCLUSION: NF2 related VS demonstrate uptake of both FLT and FDG, which is significantly increased in rapidly growing tumors. A short static FDG PET scan with standard clinical resolution and reconstruction can provide relevant information on tumor growth to aid clinical decision making.

18F-Fludeoxyglucose PET/CT in SCLC: Analysis of the CONVERT Randomized Controlled Trial.

INTRODUCTION: We used phase-3 CONVERT trial data to investigate the impact of fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in SCLC. METHODS: CONVERT randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) chemoradiotherapy. Patients were divided into two groups in this unplanned analysis: those staged with conventional imaging (contrast-enhanced thorax and abdomen CT and brain imaging with or without bone scintigraphy) and those staged with 18F-FDG PET/CT in addition. RESULTS: Data on a total of 540 patients were analyzed. Compared with patients who underwent conventional imaging (n = 231), patients also staged with 18F-FDG PET/CT (n = 309) had a smaller gross tumor volume (p = 0.003), were less likely to have an increased pretreatment serum lactate dehydrogenase level (p = 0.035), and received more chemotherapy (p = 0.026). There were no significant differences in overall (hazard ratio = 0.87, 95% confidence interval: 0.70-1.08, p = 0.192) and progression-free survival (hazard ratio = 0.87, 95% confidence interval: 0.71-1.07], p = 0.198) between patients staged with or without 18F-FDG PET/CT. In the conventional imaging group, we found no survival difference between patients staged with or without bone scintigraphy. Although there were no differences in delivered radiotherapy dose, 18F-FDG PET/CT-staged patients received lower normal tissue (lung, heart, and esophagus) radiation doses. Apart from a higher incidence of late esophagitis in patients staged with conventional imaging (for grade ≥1, 19% versus 11%; [p = 0.012]), the incidence of acute and late radiotherapy-related toxicities was not different between the two groups. CONCLUSION: In CONVERT, survival outcomes were not significantly different in patients staged with or without 18F-FDG PET/CT. However, this analysis cannot support the use or omission of 18F-FDG PET/CT owing to study limitations.

Experimental validation of estimated spatially variant radioisotope-specific point spread functions using published positron range simulations and fluorine-18 measurements.

In this work we compare spatially variant radioisotope-specific point spread functions (PSFs) derived from published positron range data with measured data using a high resolution research tomograph (HRRT). Spatially variant PSFs were measured on a HRRT for fluorine-18, carbon-11 and gallium-68 using an array of printed point sources. For gallium-68, this required modification of the original design to handle its longer positron range. Using the fluorine-18 measurements and previously published data from Monte-Carlo simulations of positron range, estimated PSFs for carbon-11 and gallium-68 were calculated and compared with experimental data. A double 3D Gaussian function was fitted to the estimated and measured data and used to model the spatially varying PSFs over the scanner field of view (FOV). Differences between the measured and estimated PSFs were quantified using the full-width-at-half-maximum (FWHM) and full-width-at-tenth-maximum (FWTM) in the tangential, radial and axial directions. While estimated PSFs were generally in agreement with the measured PSFs over the entire FOV better agreement was observed (FWHM and FWTM differences of less than 10%) when using one of the two sets of positron range simulations, especially for gallium-68 and for the FWTM. Spatially variant radioisotope specific PSFs can be accurately estimated from fluorine-18 measurements and published positron range data. We have experimentally validated this approach for carbon-11 and gallium-68, and such an approach may be applicable to other radioisotopes such as oxygen-15 for which measurements are not practical.

Comparison of SUVmax and SUVpeak based segmentation to determine primary lung tumour volume on FDG PET-CT correlated with pathology data.

PURPOSE: The aim of the study was to compare simple SUVmax and SUVpeak based segmentation methods for calculating the lung tumour volume, compared to a pathology ground truth. METHODS: Thirty patients diagnosed with early stage Non-Small Cell lung cancer (NSCLC) underwent surgical resection in the Netherlands between 2006 and 2008. FDG PET-CT scans for these patients were acquired within a median of 20 days before surgery. The tumour volume for each percentage SUVmax and SUVpeak threshold, with and without background correction, was calculated for each patient. The percentage threshold that provided the tumour volume that corresponded best with the pathology volume was considered to be the optimal threshold. The optimal thresholds were plotted as a function of tumour volume using a power law function and cross validated using the leave-one-out technique. RESULTS: The mean optimal percentage threshold was 50% ±â€¯10% and 62% ±â€¯15% for the SUVmax and SUVpeak without background correction respectively and 47% ±â€¯10% and 60 ±â€¯15% for the SUVmax and SUVpeak with background correction respectively. The optimal threshold curves could be fitted well with power law function. After cross validation the correlation between the effective tumour diameter in pathology and autosegmentation was 0.900 and 0.905 for the SUVmax and SUVpeak without background correction respectively and 0.913 and 0.908 for the SUVmax and SUVpeak with background correction respectively. CONCLUSION: No benefit was shown on clinical data for the SUVpeak based segmentation method over a SUVmax based one. Both methods can be used to determine the tumour volumes in resected NSCLC tumours.

A national survey of computed tomography doses in hybrid PET-CT and SPECT-CT examinations in the UK.

OBJECTIVES: The aim of this study was to conduct a nationwide survey of computed tomography (CT) doses for a wide range of PET-CT and single photon emission computed tomography-computed tomography (SPECT-CT) imaging procedures, with the aim of generating proposed UK national diagnostic reference levels (NDRLs). METHODS: CT protocol and dosimetry data for three PET-CT and seven SPECT-CT examinations were gathered from centres across the UK. Data were divided according to CT purpose (attenuation correction, localization or diagnostic) and third quartile values of scanner average dose metrics were used to generate suggested NDRLs for a range of examination and CT purpose combinations. Achievable doses were also established from the median of the dose distributions. RESULTS: Data were obtained from 47 centres, allowing suggested NDRLs to be produced for fluorine-18-fluorodeoxyglucose half-body PET-CT, and parathyroid, post-thyroid ablation, meta-iodobenzylguanidine/octreotide, cardiac and bone SPECT-CT examinations.Variations in dose of up to a factor of 35 were observed for a given examination/CT purpose combination. For fluorine-18-fluorodeoxyglucose half-body PET-CT examination dose levels for the three CT purposes overlapped, which highlights the variability in the way in which CT purposes are interpreted across the UK. This lack of standardization is believed to be the largest contributor to the dose variations that were observed. The survey highlighted the need for targeted optimization work in many centres. CONCLUSION: Suggested UK NDRLs and achievable doses for six common PET-CT and SPECT-CT examinations have been established as a result of this study.

Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients.

BACKGROUND AND PURPOSE: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. METHODS: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. RESULTS: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. CONCLUSION: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

[18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.

PURPOSE: Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [(18)F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [(18)F]DPA-714, it was compared directly to [(11)C]PK11195 in experimental cerebral ischaemia in rats. METHODS: Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [(11)C]PK11195 and/or [(18)F]DPA-714 under anaesthesia. RESULTS: Uptake of [(11)C]PK11195 vs [(18)F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [(11)C]PK11195 or with [(18)F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [(11)C]PK11195 and [(18)F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [(11)C]PK11195 vs [(18)F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3-1.9, 95%CI) fold by linear regression) for [(18)F]DPA-714. CONCLUSIONS: In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [(18)F]DPA-714 displayed a higher signal-to-noise ratio than [(11)C]PK11195. Our results suggest that, with the longer half-life of [(18)F] which facilitates distribution of the tracer across PET centre, [(18)F]DPA-714 is a good alternative for TSPO imaging.

Comparative study with new accuracy metrics for target volume contouring in PET image guided radiation therapy.

The impact of PET on radiation therapy is held back by poor methods of defining functional volumes of interest. Many new software tools are being proposed for contouring target volumes but the different approaches are not adequately compared and their accuracy is poorly evaluated due to the illdefinition of ground truth. This paper compares the largest cohort to date of established, emerging and proposed PET contouring methods, in terms of accuracy and variability. We emphasise spatial accuracy and present a new metric that addresses the lack of unique ground truth. 30 methods are used at 13 different institutions to contour functional VOIs in clinical PET/CT and a custom-built PET phantom representing typical problems in image guided radiotherapy. Contouring methods are grouped according to algorithmic type, level of interactivity and how they exploit structural information in hybrid images. Experiments reveal benefits of high levels of user interaction, as well as simultaneous visualisation of CT images and PET gradients to guide interactive procedures. Method-wise evaluation identifies the danger of over-automation and the value of prior knowledge built into an algorithm.

Brain inflammation is induced by co-morbidities and risk factors for stroke.

Chronic systemic inflammatory conditions, such as atherosclerosis, diabetes and obesity are associated with increased risk of stroke, which suggests that systemic inflammation may contribute to the development of stroke in humans. The hypothesis that systemic inflammation may induce brain pathology can be tested in animals, and this was the key objective of the present study. First, we assessed inflammatory changes in the brain in rodent models of chronic, systemic inflammation. PET imaging revealed increased microglia activation in the brain of JCR-LA (corpulent) rats, which develop atherosclerosis and obesity, compared to the control lean strain. Immunostaining against Iba1 confirmed reactive microgliosis in these animals. An atherogenic diet in apolipoprotein E knock-out (ApoE(-/-)) mice induced microglial activation in the brain parenchyma within 8 weeks and increased expression of vascular adhesion molecules. Focal lipid deposition and neuroinflammation in periventricular and cortical areas and profound recruitment of activated myeloid phagocytes, T cells and granulocytes into the choroid plexus were also observed. In a small, preliminary study, patients at risk of stroke (multiple risk factors for stroke, with chronically elevated C-reactive protein, but negative MRI for brain pathology) exhibited increased inflammation in the brain, as indicated by PET imaging. These findings show that brain inflammation occurs in animals, and tentatively in humans, harbouring risk factors for stroke associated with elevated systemic inflammation. Thus a "primed" inflammatory environment in the brain may exist in individuals at risk of stroke and this can be adequately recapitulated in appropriate co-morbid animal models.

Optimization of the injected activity in dynamic 3D PET: a generalized approach using patient-specific NECs as demonstrated by a series of 15O-H2O scans.

UNLABELLED: The magnitude of the injected activity (A(0)) has a direct impact on the statistical quality of PET images. This study aimed to develop a generalized method for maximizing the statistical quality of dynamic PET images by optimizing A(0). METHODS: Patient-specific noise-equivalent counts (PS-NECs) were used as a metric of the statistical quality of each time frame of a dynamic PET image. Previous methodology developed to extrapolate the NEC as a function of A(0) was extended to dynamic PET, enabling the NEC to be extrapolated as a function of both A(0) and the time after injection. This method allowed A(0) to be optimized after a single scan (at a single A(0)), by maximizing the NEC within the time interval for which the parameter estimation is most sensitive. The extrapolation method was validated by a series of (15)O-H(2)O scans of the body acquired in 3-dimensional mode. Each patient (n = 6) underwent between 3 and 6 scans at 1 bed position. The injected activities were varied over a wide range (140-840 MBq). Noise-equivalent counting rate (NECR) versus A(0) curves and the optimal injected activities were calculated from each injection. RESULTS: PS-NECR versus A(0) curves as extrapolated from different injected activities were consistent (coefficient of variation, typically <5%). The optimal injected activities for an individual, as derived from these curves, were also consistent (maximum coefficient of variation, 4.3%). For abdominal (n = 4) and chest (n = 1) scans, we found optimal injected activities of (15)O-H(2)O in the range of 220-350 MBq for estimating blood perfusion (F) and 660-1,070 MBq for estimating the volume of distribution (V(T)). Higher optimal injected activities were found in the case of a pelvic scan (n = 1; 570 MBq for F and 1,530 MBq for V(T)). CONCLUSION: PS-NECs are a valid and generic method for optimizing the injected activity in PET, allowing scanning protocols to be improved after the collection of an initial, single dynamic dataset. This generic method can be used to estimate the optimal injected activity, which is specific to the patient, tracer, PET scanner, and body region being scanned.

Neural plasticity in blind cochlear implant users.

This study, using positron emission tomography, investigates the cortical activation generated by auditory stimulation in two congenitally blind cochlear implant users. In the patient with a relatively short history of deafness, activity increased in both auditory cortices and fell in the visual cortices. The patient with a longer period of deafness had greater activation of the visual cortices than the auditory cortices. A similar pattern of activity was seen when this patient subsequently had a second cochlear implant inserted into the opposite ear. The neural pathways formed after the restoration of auditory input in the congenitally blind can activate either the auditory or visual cortices. We suggest that the visual cortical activation demonstrated is of functional significance.

Phase I evaluation of a fully human anti-alphav integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors.

PURPOSE: A fully human monoclonal antibody to anti-alpha(v) integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical studies. We assessed the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors. EXPERIMENTAL DESIGN: In this phase I trial, CNTO 95 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) was infused on days 0, 28, 35, and 42, and clinical assessments, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and [(18)F]-2-fluorodeoxyglucose positron emission tomography (FDG-PET) were done. Patients achieving stable disease or better were eligible for extended dosing every 3 weeks for up to 12 months. RESULTS: Among the 24 enrolled patients, CNTO 95 was associated with one episode of grade III and four episodes of grade II infusion-related fever (all responded to acetaminophen). Of the six patients who received extended dosing, one patient (10.0 mg/kg), with cutaneous angiosarcoma, had a 9-month partial response. Pre- and post-treatment lesion biopsies confirmed tumor cell alpha(v) integrin expression, as well as CNTO 95 penetration of the tumor and localization to tumor cells in association with reduced bcl-2 expression. A lesion in one patient (10.0 mg/kg) with stable ovarian carcinosarcoma was no longer detectable by FDG-PET by day 49. Exposure to CNTO 95 seemed to increase in a greater-than-dose-proportional manner; dose-dependent mean half-life ranged from 0.26 to 6.7 days. CONCLUSIONS: CNTO 95 was generally well tolerated. Six patients received extended therapy, including one patient with a prolonged response. Biopsy data confirmed tumor localization and pharmacodynamic activity.

A comparison of PET imaging characteristics of various copper radioisotopes.

PURPOSE: PET radiotracers which incorporate longer-lived radionuclides enable biological processes to be studied over many hours, at centres remote from a cyclotron. This paper examines the radioisotope characteristics, imaging performance, radiation dosimetry and production modes of the four copper radioisotopes, ( 60)Cu,( 61)Cu,( 62)Cu and( 64)Cu, to assess their merits for different PET imaging applications. METHODS: Spatial resolution, sensitivity, scatter fraction and noise-equivalent count rate (NEC) are predicted for( 60)Cu,( 61)Cu,( 62)Cu and( 64)Cu using a model incorporating radionuclide decay properties and scanner parameters for the GE Advance scanner. Dosimetry for( 60)Cu,( 61)Cu and( 64)Cu is performed using the MIRD model and published biodistribution data for copper(II) pyruvaldehyde bis(N(4)-methyl)thiosemicarbazone (Cu-PTSM). RESULTS: (60)Cu and( 62)Cu are characterised by shorter half-lives and higher sensitivity and NEC, making them more suitable for studying the faster kinetics of small molecules, such as Cu-PTSM.( 61)Cu and( 64)Cu have longer half-lives, enabling studies of the slower kinetics of cells and peptides and prolonged imaging to compensate for lower sensitivity, together with better spatial resolution, which partially compensates for loss of image contrast.( 61)Cu-PTSM and( 64)Cu-PTSM are associated with radiation doses similar to [(18)F]-fluorodeoxyglucose, whilst the doses for( 60)Cu-PTSM and( 62)Cu-PTSM are lower and more comparable with H(2) (15)O. CONCLUSION: The physical and radiochemical characteristics of the four copper isotopes make each more suited to some imaging tasks than others. The results presented here assist in selecting the preferred radioisotope for a given imaging application, and illustrate a strategy which can be extended to the majority of novel PET tracers.

Auditory cortical activation and speech perception in cochlear implant users: effects of implant experience and duration of deafness.

This study aimed to investigate the relationship between outcome following cochlear implantation and auditory cortical activation. It also studied the effects of length of implant use and duration of deafness on the auditory cortical activations. Cortical activity resulting from auditory stimulation was measured using [(18)F]FDG positron emission tomography. In a group of 18 experienced adult cochlear implant users, we found a positive correlation between speech perception and activations in both the primary and association auditory cortices. This correlation was present in a subgroup of experienced implant users but absent in a group of new implant users with similar speech perception abilities. There was a significant negative correlation between duration of deafness and auditory cortical activation. This study gives insights into the relationship between implant speech perception and auditory cortical activation and the influence of duration of preceding deafness and implant experience.