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The Lancet. Haematology May 2023Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus... (Review)
Review
Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.
Topics: Humans; Consensus; Nuclear Medicine; Artificial Intelligence; Hematologic Neoplasms; Molecular Imaging
PubMed: 37142345
DOI: 10.1016/S2352-3026(23)00030-3 -
A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism.European Journal of Nuclear Medicine... Nov 2016To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism. (Review)
Review
PURPOSE
To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism.
METHODS
MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded.
RESULTS
Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABA receptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson's disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABA receptors were decreased in metabolically affected cortical and subcortical regions in PSP patients.
CONCLUSIONS
PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments.
Topics: Biomarkers; Biomedical Research; Evidence-Based Medicine; Humans; Molecular Imaging; Nerve Tissue Proteins; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 27470326
DOI: 10.1007/s00259-016-3464-8 -
BMC Medical Imaging Oct 2023We aimed to perform a qualitative synthesis of evidence on the role of Ga-Pentixafor PET in atherosclerosis.
OBJECTIVE
We aimed to perform a qualitative synthesis of evidence on the role of Ga-Pentixafor PET in atherosclerosis.
METHODS
A systematic search of the PubMed and Embase databases for studies reporting the evaluation of atherosclerotic lesions by Ga-Pentixafor PET was performed with a search time frame from database creation to 2022-12-26. The diagnostic test evaluation tool QUADAS-2 was used to evaluate the quality of the included literature and to perform descriptive analyses of relevant outcome indicators.
RESULTS
A total of 6 studies with 280 patients were included. One study reported only imaging outcome metrics, while the other five studies reported imaging outcome metrics and clinical correlation metrics. For imaging outcomes, three studies reported imaging results for Ga-Pentixafor PET only, and the other three studies reported imaging results for comparative analysis of Ga-Pentixafor PET with F-FDG PET. For clinical correlation, three studies reported the correlation between tracer uptake and cardiovascular risk factors, one study reported the correlation between tracer uptake and plaque calcification, and one study reported the correlation between all three: tracer uptake, cardiovascular risk factors, and plaque calcification.
CONCLUSION
Ga-Pentixafor PET has a good imaging effect on atherosclerotic lesions, and it is a promising imaging modality that may replace F-FDG PET for atherosclerosis imaging in the future. In patients with atherosclerosis, there is a clear clinical correlation between cardiovascular risk factors, tracer uptake, and plaque calcification.
Topics: Humans; Gallium Radioisotopes; Fluorodeoxyglucose F18; Clinical Relevance; Receptors, CXCR4; Atherosclerosis; Plaque, Atherosclerotic; Positron Emission Tomography Computed Tomography; Calcinosis
PubMed: 37884885
DOI: 10.1186/s12880-023-01134-y -
Neurosurgery Jun 2021Molecular characterization of glioma has implications for prognosis, treatment planning, and prediction of treatment response. Current histopathology is limited by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Molecular characterization of glioma has implications for prognosis, treatment planning, and prediction of treatment response. Current histopathology is limited by intratumoral heterogeneity and variability in detection methods. Advances in computational techniques have led to interest in mining quantitative imaging features to noninvasively detect genetic mutations.
OBJECTIVE
To evaluate the diagnostic accuracy of machine learning (ML) models in molecular subtyping gliomas on preoperative magnetic resonance imaging (MRI).
METHODS
A systematic search was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify studies up to April 1, 2020. Methodological quality of studies was assessed using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS)-2. Diagnostic performance estimates were obtained using a bivariate model and heterogeneity was explored using metaregression.
RESULTS
Forty-four original articles were included. The pooled sensitivity and specificity for predicting isocitrate dehydrogenase (IDH) mutation in training datasets were 0.88 (95% CI 0.83-0.91) and 0.86 (95% CI 0.79-0.91), respectively, and 0.83 to 0.85 in validation sets. Use of data augmentation and MRI sequence type were weakly associated with heterogeneity. Both O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and 1p/19q codeletion could be predicted with a pooled sensitivity and specificity between 0.76 and 0.83 in training datasets.
CONCLUSION
ML application to preoperative MRI demonstrated promising results for predicting IDH mutation, MGMT methylation, and 1p/19q codeletion in glioma. Optimized ML models could lead to a noninvasive, objective tool that captures molecular information important for clinical decision making. Future studies should use multicenter data, external validation and investigate clinical feasibility of ML models.
Topics: Brain Neoplasms; Glioma; Humans; Isocitrate Dehydrogenase; Machine Learning; Magnetic Resonance Imaging; Mutation; Retrospective Studies
PubMed: 33826716
DOI: 10.1093/neuros/nyab103 -
BMC Cancer Nov 2013Molecular imaging of breast cancer is a promising emerging technology, potentially able to improve clinical care. Valid imaging targets for molecular imaging tracer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Molecular imaging of breast cancer is a promising emerging technology, potentially able to improve clinical care. Valid imaging targets for molecular imaging tracer development are membrane-bound hypoxia-related proteins, expressed when tumor growth outpaces neo-angiogenesis. We performed a systematic literature review and meta-analysis of such hypoxia marker expression rates in human breast cancer to evaluate their potential as clinically relevant molecular imaging targets.
METHODS
We searched MEDLINE and EMBASE for articles describing membrane-bound proteins that are related to hypoxia inducible factor 1α (HIF-1α), the key regulator of the hypoxia response. We extracted expression rates of carbonic anhydrase-IX (CAIX), glucose transporter-1 (GLUT1), C-X-C chemokine receptor type-4 (CXCR4), or insulin-like growth factor-1 receptor (IGF1R) in human breast disease, evaluated by immunohistochemistry. We pooled study results using random-effects models and applied meta-regression to identify associations with clinicopathological variables.
RESULTS
Of 1,705 identified articles, 117 matched our selection criteria, totaling 30,216 immunohistochemistry results. We found substantial between-study variability in expression rates. Invasive cancer showed pooled expression rates of 35% for CAIX (95% confidence interval (CI): 26-46%), 51% for GLUT1 (CI: 40-61%), 46% for CXCR4 (CI: 33-59%), and 46% for IGF1R (CI: 35-70%). Expression rates increased with tumor grade for GLUT1, CAIX, and CXCR4 (all p < 0.001), but decreased for IGF1R (p < 0.001). GLUT1 showed the highest expression rate in grade III cancers with 58% (45-69%). CXCR4 showed the highest expression rate in small T1 tumors with 48% (CI: 28-69%), but associations with size were only significant for CAIX (p < 0.001; positive association) and IGF1R (p = 0.047; negative association). Although based on few studies, CAIX, GLUT1, and CXCR4 showed profound lower expression rates in normal breast tissue and benign breast disease (p < 0.001), and high rates in carcinoma in situ. Invasive lobular carcinoma consistently showed lower expression rates (p < 0.001).
CONCLUSIONS
Our results support the potential of hypoxia-related markers as breast cancer molecular imaging targets. Although specificity is promising, combining targets would be necessary for optimal sensitivity. These data could help guide the choice of imaging targets for tracer development depending on the envisioned clinical application.
Topics: Biomarkers; Breast Neoplasms; Female; Humans; Hypoxia; Molecular Imaging; Neoplasm Grading; Publication Bias; Tumor Burden
PubMed: 24206539
DOI: 10.1186/1471-2407-13-538 -
Translational Psychiatry Mar 2016The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence... (Meta-Analysis)
Meta-Analysis Review
The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence disease risk and pharmacological response. Numerous molecular imaging studies have tested whether common genetic variants influence D2 receptor binding potential (BP) in humans, but demonstration of robust effects has been limited by small sample sizes. We performed a systematic search of published human in vivo molecular imaging studies to estimate effect sizes of common genetic variants on striatal D2 receptor BP. We identified 21 studies examining 19 variants in 11 genes. The most commonly studied variant was a single-nucleotide polymorphism in ANKK1 (rs1800497, Glu713Lys, also called 'Taq1A'). Fixed- and random-effects meta-analyses of this variant (5 studies, 194 subjects total) revealed that striatal BP was significantly and robustly lower among carriers of the minor allele (Lys713) relative to major allele homozygotes. The weighted standardized mean difference was -0.57 under the fixed-effect model (95% confidence interval=(-0.87, -0.27), P=0.0002). The normal relationship between rs1800497 and BP was not apparent among subjects with neuropsychiatric diseases. Significant associations with baseline striatal D2 receptor BP have been reported for four DRD2 variants (rs1079597, rs1076560, rs6277 and rs1799732) and a PER2 repeat polymorphism, but none have yet been tested in more than two independent samples. Our findings resolve apparent discrepancies in the literature and establish that rs1800497 robustly influences striatal D2 receptor availability. This genetic variant is likely to contribute to important individual differences in human striatal function, neuropsychiatric disease risk and pharmacological response.
Topics: Brain; Genetic Variation; Humans; Molecular Imaging; Positron-Emission Tomography; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon
PubMed: 26926883
DOI: 10.1038/tp.2016.22 -
European Urology Jan 2024In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand...
BACKGROUND
In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.
OBJECTIVE
We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.
DESIGN, SETTING, AND PARTICIPANTS
The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.
RESULTS AND LIMITATIONS
After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [Ra]RaCl remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both []FDG and PSMA PET prior to [Lu]Lu-PSMA therapy.
CONCLUSIONS
There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.
PATIENT SUMMARY
There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.
Topics: Humans; Male; Molecular Imaging; Nuclear Medicine; Positron-Emission Tomography; Precision Medicine; Prostatic Neoplasms
PubMed: 37743194
DOI: 10.1016/j.eururo.2023.09.003 -
European Journal of Vascular and... Dec 2021Previous studies on the relationship between positron emission tomography (PET) images and abdominal aortic aneurysm (AAA) progression have shown contradictory results,...
OBJECTIVE
Previous studies on the relationship between positron emission tomography (PET) images and abdominal aortic aneurysm (AAA) progression have shown contradictory results, and the objective of this study was to systematically review the role of PET in predicting AAA prognosis.
DATA SOURCES
PubMed, Embase, and Web of Science were searched for studies evaluating the correlation between PET imaging results and AAA growth, repair, or rupture.
REVIEW METHODS
Two authors independently performed the study search, data extraction, and quality assessment following a standard method.
RESULTS
Of the 11 studies included in this review, nine used F-fluorodeoxyglucose (F-FDG) PET and computed tomography (CT) imaging, whereas the remaining two used F-sodium fluoride (F-NaF) PET/CT and F-FDG PET/magnetic resonance imaging (MRI). Findings from the F-FDG PET/CT studies were contradictory. Six studies found no significant association or correlation, and two studies found a significant negative correlation between F-FDG uptake and AAA expansion. Additionally, one study found that the F-FDG uptake was statistically positively related to the expansion rate in a specific AAA subgroup whose AAAs expanded significantly. Two studies suggested that increased F-FDG uptake was significantly associated with AAA repair, while the other studies either found no association between F-FDG uptake and AAA rupture or repair or failed to report the occurrence of clinical events. One PET/CT study that used F-NaF as a tracer showed that an increased tracer uptake was significantly associated with AAA growth and clinical events. Finally, the F-FDG PET/MRI study indicated that F-FDG uptake was not significantly correlated with AAA expansion.
CONCLUSION
A definitive role for F-FDG PET imaging for AAA prognosis awaits further investigation, and new PET tracers such as F-NaF have the potential to be a promising method for predicting AAA clinical outcomes.
Topics: Aged; Aortic Aneurysm, Abdominal; Female; Fluorodeoxyglucose F18; Humans; Male; Molecular Imaging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Sodium Fluoride
PubMed: 34696984
DOI: 10.1016/j.ejvs.2021.08.010 -
European Journal of Nuclear Medicine... Jun 2024Epidemiological and logistical reasons are slowing the clinical validation of the molecular imaging biomarkers in the initial stages of neurocognitive disorders. We... (Review)
Review
PURPOSE
Epidemiological and logistical reasons are slowing the clinical validation of the molecular imaging biomarkers in the initial stages of neurocognitive disorders. We provide an updated systematic review of the recent advances (2017-2022), highlighting methodological shortcomings.
METHODS
Studies reporting the diagnostic accuracy values of the molecular imaging techniques (i.e., amyloid-, tau-, [18F]FDG-PETs, DaT-SPECT, and cardiac [123I]-MIBG scintigraphy) in predicting progression from mild cognitive impairment (MCI) to dementia were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Main eligibility criteria were as follows: (1) ≥ 50 subjects with MCI, (2) follow-up ≥ 3 years, (3) gold standard: progression to dementia or diagnosis on pathology, and (4) measures of prospective accuracy.
RESULTS
Sensitivity (SE) and specificity (SP) in predicting progression to dementia, mainly to Alzheimer's dementia were 43-100% and 63-94% for [F]FDG-PET and 64-94% and 48-93% for amyloid-PET. Longitudinal studies were lacking for less common disorders (Dementia with Lewy bodies-DLB and Frontotemporal lobe degeneration-FTLD) and for tau-PET, DaT-SPECT, and [123I]-MIBG scintigraphy. Therefore, the accuracy values from cross-sectional studies in a smaller sample of subjects (n > 20, also including mild dementia stage) were chosen as surrogate outcomes. DaT-SPECT showed 47-100% SE and 71-100% SP in differentiating Lewy body disease (LBD) from non-LBD conditions; tau-PET: 88% SE and 100% SP in differentiating DLB from Posterior Cortical Atrophy. [I]-MIBG scintigraphy differentiated LBD from non-LBD conditions with 47-100% SE and 71-100% SP.
CONCLUSION
Molecular imaging has a moderate-to-good accuracy in predicting the progression of MCI to Alzheimer's dementia. Longitudinal studies are sparse in non-AD conditions, requiring additional efforts in these settings.
Topics: Humans; Cognitive Dysfunction; Dementia; Disease Progression; Molecular Imaging
PubMed: 38355740
DOI: 10.1007/s00259-024-06631-y -
Cancer Epidemiology, Biomarkers &... Aug 2014Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations... (Meta-Analysis)
Meta-Analysis Review
Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and human epidermal growth factor receptor type 2 (HER2) overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI), and/or [(18)F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 articles, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on five or more studies and robustness in subgroup analyses were as follows: the presence of microcalcifications on mammography [pooled odds ratio (pOR), 3.14; 95% confidence interval (CI), 2.46-4.00] or ultrasound (mass-associated pOR, 2.95; 95% CI, 2.34-3.71), branching or fine linear microcalcifications (pOR, 2.11; 95% CI, 1.07-4.14) or extremely dense breasts on mammography (pOR, 1.37; 95% CI, 1.07-1.76), and washout (pOR, 1.57; 95% CI, 1.11-2.21) or fast initial kinetics (pOR, 2.60; 95% CI, 1.43-4.73) on MRI all increased the chance of HER2 overexpression. Maximum [(18)F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference, +0.76; 95% CI, 0.10-1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up.
Topics: Breast Neoplasms; Diagnostic Imaging; Female; Humans; Phenotype; Receptor, ErbB-2
PubMed: 24807204
DOI: 10.1158/1055-9965.EPI-13-1170