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Seminars in Musculoskeletal Radiology Dec 2023The diagnosis and understanding of pain is challenging in clinical practice. Assessing pain relies heavily on self-reporting by patients, rendering it inherently... (Review)
Review
The diagnosis and understanding of pain is challenging in clinical practice. Assessing pain relies heavily on self-reporting by patients, rendering it inherently subjective. Traditional clinical imaging methods such as computed tomography and magnetic resonance imaging can only detect anatomical abnormalities, offering limited sensitivity and specificity in identifying pain-causing conditions. Radiotracers play a vital role in molecular imaging that aims to identify abnormal biological processes at the cellular level, even in apparently normal anatomical structures. Therefore, molecular imaging is an important area of research as a prospective diagnostic modality for pain-causing pathophysiology. We present a mini review of the current knowledge base regarding radiotracers for identification of pain in vivo. We also describe radiocaine, a novel positron emission tomography imaging agent for sodium channels that has shown great potential for identifying/labeling pain-producing nerves and producing an objectively measurable pain intensity signal.
Topics: Humans; Prospective Studies; Positron-Emission Tomography; Tomography, X-Ray Computed; Radiopharmaceuticals; Pain
PubMed: 37935212
DOI: 10.1055/s-0043-1775743 -
American Journal of Rhinology & Allergy Sep 2023Positron emission tomography (PET) scan is a valuable imaging modality widely used in the management of cancers. Its usage is well defined for most head and neck... (Review)
Review
BACKGROUND
Positron emission tomography (PET) scan is a valuable imaging modality widely used in the management of cancers. Its usage is well defined for most head and neck malignancies. However, there is a lack of consensus regarding the utility of PET scan for sinonasal malignancies. This is highlighted by the latest international consensus statement on endoscopic skull base surgery.
OBJECTIVE
This systematic review aims to clarify the role of PET scan in the management of sinonasal malignancies.
METHODS
We conducted a comprehensive literature search using PubMed, MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane databases for research studies of interest. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) updated statement was used to guide the review.
RESULTS
In total, 1807 articles were assessed for eligibility. Thirty-nine original papers, published between 2004 and 2021, met inclusion criteria. Seven articles focused on the role of PET scan for inverted papilloma, 23 for sinonasal carcinoma, 4 for melanoma, and 3 for lymphoma, and finally, 3 articles focused on the use of specific PET scan tracers for sinonasal malignancies. Qualitative summaries for each potential role of PET scans were provided. In general, included studies were retrospective in nature with low level of evidence.
CONCLUSIONS
In general, and across all types of sinonasal malignancies, PET scan yielded positive results regarding detection and initial staging. It was also considered as the modality of choice for detection of distant metastases, except in the case of sinonasal lymphoma. PET scan's main limit resides in its inability to detect lesions in or close to the metabolic activity of the brain.
Topics: Humans; Positron Emission Tomography Computed Tomography; Retrospective Studies; Positron-Emission Tomography; Paranasal Sinus Neoplasms; Lymphoma
PubMed: 37229633
DOI: 10.1177/19458924231177854 -
Atherosclerosis Nov 2023Asymptomatic atherosclerosis begins early in life and may progress in a sex-specific manner to become the major cause of cardiovascular morbidity and death. As... (Review)
Review
Asymptomatic atherosclerosis begins early in life and may progress in a sex-specific manner to become the major cause of cardiovascular morbidity and death. As diagnostic tools to evaluate atherosclerosis in the macrocirculation, we discuss imaging methods (in terms of computed tomography, positron emission tomography, intravascular ultrasound, magnetic resonance imaging, and optical coherence tomography), along with derived scores (Agatston, Gensini, Leaman, Syntax), and also hemodynamic indices of vascular stiffness (including flow-mediated dilation, shear stress, pulse pressure, augmentation index, arterial distensibility), assessment of plaque properties (composition, erosion, rupture), stenosis measures such as fractional flow reserve. Moreover, biomarkers including matrix metalloproteinases, vascular endothelial growth factors and miRNAs, as well as the impact of machine learning support, are described. Special attention is given to age-related aspects and sex-specific characteristics, along with clinical implications. Knowledge gaps are identified and directions for future research formulated.
Topics: Female; Humans; Male; Fractional Flow Reserve, Myocardial; Sex Characteristics; Atherosclerosis; Plaque, Atherosclerotic; Positron-Emission Tomography
PubMed: 37783644
DOI: 10.1016/j.atherosclerosis.2023.117275 -
Nuclear Medicine and Biology 2023Cell death is fundamental in health and disease and resisting cell death is a hallmark of cancer. Treatment of malignancy aims to cause cancer cell death, however... (Review)
Review
Cell death is fundamental in health and disease and resisting cell death is a hallmark of cancer. Treatment of malignancy aims to cause cancer cell death, however current clinical imaging of treatment response does not specifically image cancer cell death but assesses this indirectly either by changes in tumor size (using x-ray computed tomography) or metabolic activity (using 2-[F]fluoro-2-deoxy-glucose positron emission tomography). The ability to directly image tumor cell death soon after commencement of therapy would enable personalised response adapted approaches to cancer treatment that is presently not possible with current imaging, which is in many circumstances neither sufficiently accurate nor timely. Several cell death pathways have now been identified and characterised that present multiple potential targets for imaging cell death including externalisation of phosphatidylserine and phosphatidylethanolamine, caspase activation and La autoantigen redistribution. However, targeting one specific cell death pathway carries the risk of not detecting cell death by other pathways and it is now understood that cancer treatment induces cell death by different and sometimes multiple pathways. An alternative approach is targeting the cell death phenotype that is "agnostic" of the death pathway. Cell death phenotypes that have been targeted for cell death imaging include loss of plasma membrane integrity and dissipation of the mitochondrial membrane potential. Targeting the cell death phenotype may have the advantage of being a more sensitive and generalisable approach to cancer cell death imaging. This review describes and summarises the approaches and radiopharmaceuticals investigated for imaging cell death by targeting cell death pathways or cell death phenotype.
Topics: Humans; Fluorodeoxyglucose F18; Neoplasms; Positron-Emission Tomography; Tomography, X-Ray Computed; Radiopharmaceuticals
PubMed: 37598518
DOI: 10.1016/j.nucmedbio.2023.108380 -
Scientific Reports Oct 2023Primary mediastinal germ cell tumor (MGCT) is an uncommon tumor. Although it has histology similar to that of gonadal germ cell tumor (GCT), the prognosis for MGCT is...
Primary mediastinal germ cell tumor (MGCT) is an uncommon tumor. Although it has histology similar to that of gonadal germ cell tumor (GCT), the prognosis for MGCT is generally worse than that for gonadal GCT. We performed visual assessment and quantitative analysis of [F]fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG PET/CT) for MGCTs. A total of 35 MGCT patients (age = 33.1 ± 16.8 years, F:M = 16:19) who underwent preoperative PET/CT were retrospectively reviewed. The pathologic diagnosis of MGCTs identified 24 mature teratomas, 4 seminomas, 5 yolk sac tumors, and 2 mixed germ cell tumors. Visual assessment was performed by categorizing the uptake intensity, distribution, and contour of primary MGCTs. Quantitative parameters including the maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter were compared between benign and malignant MGCTs. On visual assessment, the uptake intensity was the only significant parameter for differentiating between benign and malignant MGCTs (p = 0.040). In quantitative analysis, the SUVmax (p < 0.001), TBR (p < 0.001), MTV (p = 0.033), and TLG (p < 0.001) showed significantly higher values for malignant MGCTs compared with benign MGCTs. In receiver operating characteristic (ROC) curve analysis of these quantitative parameters, the SUVmax had the highest area under the curve (AUC) (AUC = 0.947, p < 0.001). Furthermore, the SUVmax could differentiate between seminomas and nonseminomatous germ cell tumors (p = 0.042) and reflect serum alpha fetoprotein (AFP) levels (p = 0.012). The visual uptake intensity and SUVmax on [F]FDG PET/CT showed discriminative ability for benign and malignant MGCTs. Moreover, the SUVmax may associate with AFP levels.
Topics: Male; Humans; Adolescent; Young Adult; Adult; Middle Aged; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Radiopharmaceuticals; Retrospective Studies; Seminoma; alpha-Fetoproteins; Positron-Emission Tomography; Prognosis; Testicular Neoplasms; Tumor Burden; Glycolysis
PubMed: 37848723
DOI: 10.1038/s41598-023-44913-x -
International Journal of Molecular... Dec 2023Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and... (Review)
Review
Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, autoimmune diseases, pulmonary and cancer. Inflammation in the brain is marked by the upregulation of translocator protein (TSPO) in microglia. High TSPO levels are also found, for example, in macrophages in cases of rheumatoid arthritis and in malignant tumor cells compared to their relatively low physiological expression. The same applies for cyclooxgenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable the monitoring of the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers, not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases such as rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.
Topics: Humans; Cyclooxygenase 2; Noncommunicable Diseases; Positron-Emission Tomography; Brain; Biomarkers; Arthritis, Rheumatoid; Inflammation; Receptors, GABA; Carrier Proteins
PubMed: 38139248
DOI: 10.3390/ijms242417419 -
Pain Oct 2023This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as... (Observational Study)
Observational Study
This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as measured with positron emission tomography using [ 18 F]DPA-714, a second-generation radioligand for the translocator protein (TSPO). Fifteen women with FM and 10 HCs underwent neuroimaging. Distribution volume (V T ) was calculated for in 28 regions of interest (ROIs) using Logan graphical analysis and compared between groups using multiple linear regressions. Group (FM vs HC) was the main predictor of interest and TSPO binding status (high- vs mixed-affinity) was added as a covariate. The FM group had higher V T in the right postcentral gyrus ( b = 0.477, P = 0.033), right occipital gray matter (GM; b = 0.438, P = 0.039), and the right temporal GM ( b = 0.466, P = 0.042). The FM group also had lower V T than HCs in the left isthmus of the cingulate gyrus ( b = -0.553, P = 0.014). In the subgroup of high-affinity binders, the FM group had higher V T in the bilateral precuneus, postcentral gyrus, parietal GM, occipital GM, and supramarginal gyrus. Group differences in the right parietal GM were associated with decreased quality of life, higher pain severity and interference, and cognitive problems. In support of our hypothesis, we found increased radioligand binding (V T ) in the FM group compared with HCs in several brain regions regardless of participants' TSPO binding status. The ROIs overlapped with prior reports of increased TSPO binding in FM. Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain.
Topics: Humans; Female; Fibromyalgia; Neuroinflammatory Diseases; Quality of Life; Positron-Emission Tomography; Brain; Receptors, GABA
PubMed: 37326674
DOI: 10.1097/j.pain.0000000000002927 -
Journal of Nuclear Medicine : Official... Jul 2023Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC)...
Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC) accounts for 80% of primary liver cancer cases. Glypican-3 (GPC3) is a heparan sulfate proteoglycan that histopathologically defines HCC and represents an attractive tumor-selective marker for radiopharmaceutical imaging and therapy for this disease. Single-domain antibodies are a promising scaffold for imaging because of their favorable pharmacokinetic properties, good tumor penetration, and renal clearance. Although conventional lysine-directed bioconjugation can be used to yield conjugates for radiolabeling full-length antibodies, this stochastic approach risks negatively affecting target binding of the smaller single-domain antibodies. To address this challenge, site-specific approaches have been explored. Here, we used conventional and sortase-based site-specific conjugation methods to engineer GPC3-specific human single-domain antibody (HN3) PET probes. Bifunctional deferoxamine (DFO) isothiocyanate was used to synthesize native HN3 (nHN3)-DFO. Site-specifically modified HN3 (ssHN3)-DFO was engineered using sortase-mediated conjugation of triglycine-DFO chelator and HN3 containing an LPETG C-terminal tag. Both conjugates were radiolabeled with Zr, and their binding affinity in vitro and target engagement of GPC3-positive (GPC3) tumors in vivo were determined. Both Zr-ssHN3 and Zr-nHN3 displayed nanomolar affinity for GPC3 in vitro. Biodistribution and PET/CT image analysis in mice bearing isogenic A431 and A431-GPC3 xenografts, as well as in HepG2 liver cancer xenografts, showed that both conjugates specifically identify GPC3 tumors. Zr-ssHN3 exhibited more favorable biodistribution and pharmacokinetic properties, including higher tumor uptake and lower liver accumulation. Comparative PET/CT studies on mice imaged with both F-FDG and Zr-ssHN3 showed more consistent tumor accumulation for the single-domain antibody conjugate, further establishing its potential for PET imaging. Zr-ssHN3 showed clear advantages in tumor uptake and tumor-to-liver signal ratio over the conventionally modified Zr-nHN3 in xenograft models. Our results establish the potential of HN3-based single-domain antibody probes for GPC3-directed PET imaging of liver cancers.
Topics: Humans; Animals; Mice; Liver Neoplasms; Carcinoma, Hepatocellular; Single-Domain Antibodies; Radioisotopes; Glypicans; Positron Emission Tomography Computed Tomography; Antibodies, Monoclonal; Tissue Distribution; Cell Line, Tumor; Positron-Emission Tomography; Zirconium
PubMed: 36997331
DOI: 10.2967/jnumed.122.265171 -
Ga-FAPI-04 Positron Emission Tomography Distinguishes Malignancy From F-FDG-Avid Colorectal Lesions.International Journal of Radiation... Jan 2024Lesions with a high uptake of F-fluorodeoxyglucose (F-FDG) on positron emission tomography-computed tomography (PET-CT) can be benign and malignant. New radiotracers,...
PURPOSE
Lesions with a high uptake of F-fluorodeoxyglucose (F-FDG) on positron emission tomography-computed tomography (PET-CT) can be benign and malignant. New radiotracers, such as the gallium 68 (Ga)-labeled fibroblast activation protein inhibitor 4 (FAPI-04), could be used to diagnose colorectal carcinoma. This study aimed to evaluate the efficacy of Ga-FAPI-04 PET in differentiating benign from malignant F-FDG-avid colorectal lesions.
METHODS AND MATERIALS
An azoxymethane/dextran sodium sulfate (AOM/DSS)-induced rat colorectal tumor model was developed. Double-tracer Ga-FAPI-04 and F-FDG PET-CT were applied in the rat model and 22 patients. The PET-CT data were analyzed with enteroscopy, histopathologic observations, immunohistochemistry (IHC) staining, and radioautography results. One hundred seventy-two patients with pathologically confirmed colorectal lesions were enrolled in FAP IHC staining.
RESULTS
We found that Ga-FAPI-04 PET-CT imaging accurately distinguished the malignant from benign inflammatory lesions in an AOM/DSS-induced rat colorectal tumor model. Of 22 patients with gastric cancer but without colorectal carcinoma, 8 had F-FDG uptake in the colorectum, but Ga-FAPI-04 PET was negative in these sites. An inflammatory lesion or adenoma did not interfere with Ga-FAPI-04 PET imaging. Among the F-FDG-avid colorectal lesions, 80 of 94 pathologically malignant lesions (85.1%) were FAP-positive, and only 16 of the 78 premalignant or benign lesions (20.5%) had a weak Ga-FAPI-04 uptake.
CONCLUSIONS
Ga-FAPI-04 PET-CT could be used to distinguish between benign and malignant F-FDG-avid colorectal lesions.
Topics: Humans; Animals; Rats; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes; Positron-Emission Tomography; Quinolines; Colorectal Neoplasms; Azoxymethane
PubMed: 37634891
DOI: 10.1016/j.ijrobp.2023.08.019 -
Scientific Reports Aug 2023Convolutional neural networks (CNNs) may improve response prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to investigate the feasibility...
Convolutional neural networks (CNNs) may improve response prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to investigate the feasibility of a CNN using maximum intensity projection (MIP) images from F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) baseline scans to predict the probability of time-to-progression (TTP) within 2 years and compare it with the International Prognostic Index (IPI), i.e. a clinically used score. 296 DLBCL F-FDG PET/CT baseline scans collected from a prospective clinical trial (HOVON-84) were analysed. Cross-validation was performed using coronal and sagittal MIPs. An external dataset (340 DLBCL patients) was used to validate the model. Association between the probabilities, metabolic tumour volume and Dmax was assessed. Probabilities for PET scans with synthetically removed tumors were also assessed. The CNN provided a 2-year TTP prediction with an area under the curve (AUC) of 0.74, outperforming the IPI-based model (AUC = 0.68). Furthermore, high probabilities (> 0.6) of the original MIPs were considerably decreased after removing the tumours (< 0.4, generally). These findings suggest that MIP-based CNNs are able to predict treatment outcome in DLBCL.
Topics: Humans; Artificial Intelligence; Fluorodeoxyglucose F18; Lymphoma, Large B-Cell, Diffuse; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prognosis; Prospective Studies; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Clinical Trials as Topic
PubMed: 37573446
DOI: 10.1038/s41598-023-40218-1