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- Adamczuk, Katarzyna, et al.
(author)
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Amyloid imaging in cognitively normal older adults : comparison between F-18-flutemetamol and C-11-Pittsburgh compound B
- 2016
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:1, s. 142-151
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Journal article (peer-reviewed)abstract
- Purpose Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: F-18-flutemetamol and C-11-Pittsburgh compound B (PIB). Methods In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on F-18-flutemetamol versus C-11-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between F-18-flutemetamol and C-11-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. Results Binary classification based on semiquantitative assessment was concordant between F-18-flutemetamol and C-11-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between F-18-flutemetamol and C-11-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. Conclusion For the definition of preclinical AD based on F-18-flutemetamol, concordance with C-11-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region.
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- Altai, Mohamed, et al.
(author)
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Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with 188-Re
- 2013
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:Suppl. 2, s. S219-S220
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Journal article (other academic/artistic)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1±0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172±32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
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- Andersson, JLR, et al.
(author)
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A multivariate approach to registration of dissimilar tomographic images
- 1999
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In: European Journal of Nuclear Medicine. - : SPRINGER VERLAG. - 0340-6997 .- 1432-105X .- 1619-7070 .- 1619-7089. ; 26:7, s. 718-733
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Journal article (peer-reviewed)abstract
- We devised a method to allow for retrospective registration of tomographic images with very different information content, the main emphasis being on sets of positron emission tomography images obtained with different tracers. A multivariate cost-function
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- Andersson, M., et al.
(author)
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Dynamic absorbed dose calculations to the urinary bladder wall for the ICRP compartmental models of iodide and technetium
- 2019
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:SUPPL 1, s. S281-S282
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Journal article (other academic/artistic)abstract
- Aim/Introduction: The urinary bladder wall is a radiosensitive organ that can receive a high absorbed dose from radiopharmaceuticals used even in diagnostic nuclear medicine. The commonly used method to calculate the absorbed dose to the urinary bladder wall is to apply absorbed fractions or S-values derived for a static volume of the content e.g. 200 mL for adult males. However, there are some dynamic models to estimate the photon and electron absorbed dose contributions to the inner surface or the mean absorbed dose to the bladder wall. These models have only been applied on adults and use descriptive biokinetic models for the transfer of radionuclides. The aim of this work is to estimate the absorbed dose, based on Monte Carlo-simulated dynamic urinary bladders and the ICRP compartmental biokinetic models of iodide and pertechnetate. The calculations include sex specific absorbeddose and estimations for preadults of 15- 10- 5- 1-year and newborn.Materials and Methods: S-values were calculated for different volumes of the content with a fix mass of the wall. As an approximation a spherical shape was assumed. Calculations were based on anatomical and physiological data of the reference sets of values given in ICRP Publication 89. The reference values were given for both male and female subjects of six different ages: newborn, 1-, 5-, 10-, 15-years, and adult. The elemental compositions of the urinary bladder wall and content were taken from the ICRP Publication 110.Results: For adult male assuming a urinary flow rate of 1600 ml/day, an initial urine volume of 100 ml, a voiding volume at 300 ml and a residual volume of 30 ml, the cumulated activity will for intravenously administered activity of Tc-99m pertechnetate be 30 % lower than assuming a 3.5 hour voiding interwall. The absorbed dose to the urinary bladder wall will be 64% lower also applying the dynamic S-values on the dynamic case. Using the same biological parameters for intravenous intake of I-131 iodide, the cumulated activity will be 60 % higher for the dynamic case and the mean absorbed dose to the urinary bladder wall 30 % lower.Conclusion: This project aims to perform more realistic calculation of absorbed dose to the urinary bladder calculations. This is done by tracking the activity in the urinary content at each time on compartment models and applying the time dependent activity to urinary flow and Monte Carlo simulated S-values.
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- Ashton, Nicholas J., et al.
(author)
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The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers
- 2021
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48, s. 2140-2156
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Journal article (peer-reviewed)abstract
- Purpose The development of blood biomarkers that reflect Alzheimer's disease (AD) pathophysiology (phosphorylated tau and amyloid-beta) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. Methods A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Results Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for A beta remains to be partially achieved. Full and partial achievement has been assigned to p-tau and A beta, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. Conclusions Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 - with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.
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- Badoud, Simon, et al.
(author)
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Distinct spatiotemporal patterns for disease duration and stage in Parkinson's disease
- 2016
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:3, s. 509-516
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Journal article (peer-reviewed)abstract
- Purpose To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson's disease (PD). Methods This retrospective study included 970 consecutive patients undergoing I-123-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 +/- 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 +/- 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other. Results Increasing disease stage was associated with an exponential decrease in I-123-ioflupane uptake (R (2) = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p < 0.0001), whereas increasing disease duration was associated with a linear decrease in I-123-ioflupane uptake (p < 0.0001; R (2) = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001). Conclusion We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 I-123-ioflupane SPECT scans can be used for clinical and research applications.
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- Bajc, Marika, et al.
(author)
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EANM guidelines for ventilation/perfusion scintigraphy : Part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography.
- 2009
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:8, s. 1356-1370
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Journal article (peer-reviewed)abstract
- Pulmonary embolism (PE) can only be diagnosed with imaging techniques, which in practice is performed using ventilation/perfusion scintigraphy (V/P(SCAN)) or multidetector computed tomography of the pulmonary arteries (MDCT). The epidemiology, natural history, pathophysiology and clinical presentation of PE are briefly reviewed. The primary objective of Part 1 of the Task Group's report was to develop a methodological approach to and interpretation criteria for PE. The basic principle for the diagnosis of PE based upon V/P(SCAN) is to recognize lung segments or subsegments without perfusion but preserved ventilation, i.e. mismatch. Ventilation studies are in general performed after inhalation of Krypton or technetium-labelled aerosol of diethylene triamine pentaacetic acid (DTPA) or Technegas. Perfusion studies are performed after intravenous injection of macroaggregated human albumin. Radiation exposure using documented isotope doses is 1.2-2 mSv. Planar and tomographic techniques (V/P(PLANAR) and V/P(SPECT)) are analysed. V/P(SPECT) has higher sensitivity and specificity than V/P(PLANAR). The interpretation of either V/P(PLANAR) or V/P(SPECT) should follow holistic principles rather than obsolete probabilistic rules. PE should be reported when mismatch of more than one subsegment is found. For the diagnosis of chronic PE, V/P(SCAN) is of value. The additional diagnostic yield from V/P(SCAN) includes chronic obstructive lung disease (COPD), heart failure and pneumonia. Pitfalls in V/P(SCAN) interpretation are considered. V/P(SPECT) is strongly preferred to V/P(PLANAR) as the former permits the accurate diagnosis of PE even in the presence of comorbid diseases such as COPD and pneumonia. Technegas is preferred to DTPA in patients with COPD.
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- Bajc, Marika, et al.
(author)
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EANM guidelines for ventilation/perfusion scintigraphy : Part 2. Algorithms and clinical considerations for diagnosis of pulmonary emboli with V/P(SPECT) and MDCT.
- 2009
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089.
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Journal article (peer-reviewed)abstract
- As emphasized in Part 1 of these guidelines, the diagnosis of pulmonary embolism (PE) is confirmed or refuted using ventilation/perfusion scintigraphy (V/P(SCAN)) or multidetector computed tomography of the pulmonary arteries (MDCT). To reduce the costs, the risks associated with false-negative and false-positive diagnoses, and unnecessary radiation exposure, preimaging assessment of clinical probability is recommended. Diagnostic accuracy is approximately equal for MDCT and planar V/P(SCAN) and better for tomography (V/P(SPECT)). V/P(SPECT) is feasible in about 99% of patients, while MDCT is often contraindicated. As MDCT is more readily available, access to both techniques is vital for the diagnosis of PE. V/P(SPECT) gives an effective radiation dose of 1.2-2 mSv. For V/P(SPECT), the effective dose is about 35-40% and the absorbed dose to the female breast 4% of the dose from MDCT performed with a dose-saving protocol. V/P(SPECT) is recommended as a first-line procedure in patients with suspected PE. It is particularly favoured in young patients, especially females, during pregnancy, and for follow-up and research.
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- Bajc, Marika, et al.
(author)
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Letter to editor
- 2020
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 47, s. 1643-1644
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Journal article (other academic/artistic)
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38. |
- Bajc, Marika, et al.
(author)
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Perfusion SPECT in patients with suspected pulmonary embolism.
- 2013
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:9, s. 1432-1437
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Journal article (peer-reviewed)abstract
- PURPOSE: Ventilation/perfusion tomography (V/PSPECT), with new interpretation criteria and newer tracers for ventilation imaging, has markedly improved the diagnostic yield in acute pulmonary embolism (PE). Here, we evaluated the diagnostic performance of perfusion SPECT (PSPECT) without ventilation imaging. METHODS: We studied 152 patients with clinically suspected PE who had been examined with both V/PSPECT and multidetector computed tomographic angiography (MD-CTA). The diagnosis or exclusion of PE was decided by the referring clinician based on both the V/PSPECT and/or MD-CTA findings in combination with the clinical findings. PSPECT images were retrospectively examined by a physician with experience in the interpretation of planar perfusion scans who was blinded to clinical, V/PSPECT and MD-CTA data. PSPECT images were interpreted without the aid of chest radiography. All the patients who were deemed to have PE were given anticoagulant therapy. RESULTS: Of the 152 patients, 59 (39 %) received a final diagnosis of PE, and 19 (32 %) had associated cardiopulmonary diseases such as pneumonia, COPD, or left heart failure. PSPECT correctly identified 53 (90 %) of the 59 patients with PE. The specificity was 88 of 93 (95 %). None of the PSPECT images was rated nondiagnostic. PSPECT yielded an overall diagnostic accuracy of 93 % (95 % confidence interval, CI, 87-96 %). At the observed PE prevalence of 39 %, the positive and negative predictive values of PSPECT were 91 % (95 % CI, 80-97 %) and 94 % (95 % CI, 86-97 %), respectively. CONCLUSION: In managing critically ill patients, PSPECT might be a valid alternative to V/PSPECT or MD-CTA since it was able to identify most patients with PE with a low false-positive rate and no inconclusive results.
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- Bajc, Marika, et al.
(author)
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V/P SPECT as a diagnostic tool for pregnant women with suspected pulmonary embolism.
- 2015
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 42:8, s. 1325-1330
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Journal article (peer-reviewed)abstract
- The purpose of the study was to assess the prevalence of pulmonary embolism (PE) and other lung diseases among pregnant women with suspected PE and to calculate the radiation exposure to patient and fetus in this population. As a secondary aim, we evaluated the negative predictive value of a normal ventilation/perfusion single photon emission computed tomography (V/P SPECT) examination in pregnancy.
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- Bar-Sever, Zvi, et al.
(author)
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Guidelines on nuclear medicine imaging in neuroblastoma
- 2018
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 45:11, s. 2009-2024
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Journal article (peer-reviewed)abstract
- Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on I-123-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with F-18-FDG, F-18-DOPA and Ga-68-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.
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- Barrington, Sally F., et al.
(author)
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Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma
- 2010
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 37:10, s. 1824-1833
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Journal article (peer-reviewed)abstract
- To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries. Four centres reported scans from 50 patients with stage II-IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using 'normal' mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading). There was agreement that the response scan was 'positive' or 'negative' for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74-0.96) for conservative reading and 0.79 (95% CI 0.67-0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively. The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.
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- Benjegård, S A, et al.
(author)
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Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.
- 2001
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In: European journal of nuclear medicine. - : Springer Science and Business Media LLC. - 0340-6997 .- 1619-7070 .- 1619-7089. ; 28:10, s. 1456-62
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Journal article (peer-reviewed)abstract
- Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(T1) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(T1) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(T1) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.
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- Berglund, Hanna, et al.
(author)
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p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts
- 2023
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089.
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Journal article (peer-reviewed)abstract
- PurposeMolecular radiotherapy is a treatment modality that is highly suitable for targeting micrometastases and [177Lu]Lu-DOTATATE is currently being explored as a potential novel treatment option for high-risk neuroblastoma. p53 is a key player in the proapoptotic signalling in response to radiation-induced DNA damage and is therefore a potential target for radiosensitisation.MethodsThis study investigated the use of the p53 stabilising peptide VIP116 and [177Lu]Lu-DOTATATE, either alone or in combination, for treatment of neuroblastoma tumour xenografts in mice. Initially, the uptake of [177Lu]Lu-DOTATATE in the tumours was confirmed, and the efficacy of VIP116 as a monotherapy was evaluated. Subsequently, mice with neuroblastoma tumour xenografts were treated with placebo, VIP116, [177Lu]Lu-DOTATATE or a combination of both agents.ResultsThe results demonstrated that monotherapy with either VIP116 or [177Lu]Lu-DOTATATE significantly prolonged median survival compared to the placebo group (90 and 96.5 days vs. 50.5 days, respectively). Notably, the combination treatment further improved median survival to over 120 days. Furthermore, the combination group exhibited the highest percentage of complete remission, corresponding to a twofold increase compared to the placebo group. Importantly, none of the treatments induced significant nephrotoxicity. Additionally, the therapies affected various molecular targets involved in critical processes such as apoptosis, hypoxia and angiogenesis.ConclusionIn conclusion, the combination of VIP116 and [177Lu]Lu-DOTATATE presents a promising novel treatment approach for neuroblastoma. These findings hold potential to advance research efforts towards a potential cure for this vulnerable patient population.
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