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Breast Cancer Research : BCR Jun 2024Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune...
Evaluating the immunologically "cold" tumor microenvironment after treatment with immune checkpoint inhibitors utilizing PET imaging of CD4 + and CD8 + T cells in breast cancer mouse models.
BACKGROUND
Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune checkpoint blockade (ICB) in immunologically "hot" tumors. However, immune dynamics in the low T-cell infiltrating "cold" tumor immune microenvironment during ICB remain poorly understood. This study uses molecular imaging to evaluate changes in CD4 + T cells and CD8 + T cells during ICB in breast cancer models and examines biomarkers of response.
METHODS
[Zr]Zr-DFO-CD4 and [Zr]Zr-DFO-CD8 radiotracers were used to quantify changes in intratumoral and splenic CD4 T cells and CD8 T cells in response to ICB treatment in 4T1 and MMTV-HER2 mouse models, which represent immunologically "cold" tumors. A correlation between PET quantification metrics and long-term anti-tumor response was observed. Further biological validation was obtained by autoradiography and immunofluorescence.
RESULTS
Following ICB treatment, an increase in the CD8-specific PET signal was observed within 6 days, and an increase in the CD4-specific PET signal was observed within 2 days in tumors that eventually responded to immunotherapy, while no significant differences in CD4 or CD8 were found at the baseline of treatment that differentiated responders from nonresponders. Furthermore, mice whose tumors responded to ICB had a lower CD8 PET signal in the spleen and a higher CD4 PET signal in the spleen compared to non-responders. Intratumoral spatial heterogeneity of the CD8 and CD4-specific PET signals was lower in responders compared to non-responders. Finally, PET imaging, autoradiography, and immunofluorescence signals were correlated when comparing in vivo imaging to ex vivo validations.
CONCLUSIONS
CD4- and CD8-specific immuno-PET imaging can be used to characterize the in vivo distribution of CD4 + and CD8 + T cells in response to immune checkpoint blockade. Imaging metrics that describe the overall levels and distribution of CD8 + T cells and CD4 + T cells can provide insight into immunological alterations, predict biomarkers of response to immunotherapy, and guide clinical decision-making in those tumors where the kinetics of the response differ.
PubMed: 38918836
DOI: 10.1186/s13058-024-01844-3 -
Scientific Reports Jun 2024Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with...
Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with mediastinal involvement from the EuroNet-PHL-C1 trial and explored correlations of HDV with patient characteristics, mediastinal tumor volume and progression-free survival. HDV occurred in 350 of 1178 patients (29.7%), typically in larger mediastinal volumes. There were different patterns in appearance with single lesions found in 243 patients (69.4%), multiple lesions in 107 patients (30.6%). Well delineated lesions were found in 248 cases (70.1%), diffuse lesions were seen in 102 cases (29.1%). Clinically, B symptoms occurred more often in patients with HDV (47.7% compared to 35.0% without HDV (p = 0.039)) and patients with HDV tended to be in higher risk groups. Inadequate overall early-F-FDG-PET-response was strongly correlated with the occurrence of hypodense lesions (p < 0.001). Patients with total HDV > 40 ml (n = 80) had a 5 year PFS of 79.6% compared to 89.7% (p = 0.01) in patients with HDV < 40 ml or no HDV. This difference in PFS is not caused by treatment group alone. HDV is a common phenomenon in HL with mediastinal involvement.
Topics: Humans; Male; Female; Hodgkin Disease; Adult; Mediastinal Neoplasms; Middle Aged; Tomography, X-Ray Computed; Young Adult; Aged; Adolescent; Mediastinum; Fluorodeoxyglucose F18; Positron-Emission Tomography; Progression-Free Survival
PubMed: 38918503
DOI: 10.1038/s41598-024-64253-8 -
Neurocritical Care Jun 2024To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission...
BACKGROUND
To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better.
METHODS
We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5 T or 3 T. Healthy controls were investigated with both 1.5 T and 3 T ASL-MRI.
RESULTS
We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56 years, range 18-82 years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50 years, range 21-77 years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2 mL/100 g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant.
CONCLUSIONS
CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.
PubMed: 38918338
DOI: 10.1007/s12028-024-02031-0 -
European Journal of Obstetrics,... Jun 2024Despite the profound impact of endometriosis worldwide, delays in diagnosis and suboptimal surveillance techniques are well-recognised issues. Case studies have reported... (Review)
Review
Despite the profound impact of endometriosis worldwide, delays in diagnosis and suboptimal surveillance techniques are well-recognised issues. Case studies have reported incidental uptake of F-FDG PET tracer in endometriotic lesions. However, the utility of PET imaging as a non-invasive diagnostic tool for endometriosis is currently unclear. The purpose of this systematic review was to summarise the existing evidence and determine the value of available PET scanning techniques in the detection and monitoring of endometriosis. MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science were searched from conception to 05/03/23. Eligible studies included participants with a history of known or suspected endometriosis who underwent a PET scan for any indication. All PET tracers and protocols were eligible. Outcomes included correlation of PET tracer uptake with the presence of endometriosis seen at laparoscopy or confirmed on histology, sensitivity of tracer uptake, specificity of tracer uptake, site of lesions with tracer uptake, stage of lesions with tracer uptake, SUV of endometriosis lesions and adverse reactions to PET imaging. The protocol for this review was registered with PROSPERO (ID: CRD42023405260). Eight studies describing 110 participants were eligible for inclusion. Six studies assessed F-FDG with combined PET-CT, one study assessed F-FDG PET alone, and the remaining study assessed PET-CT with an alternative tracer, Ga-DOTATATE. For F-FDG imaging, the correlation of PET avidity with lesions or sites of endometriosis ranged from 0-55 %. Pre-operative Ga-DOTATATE PET-CT detected endometriosis in 33 % of cases. All included studies were cohort studies, six were assessed to have low risk of bias, one with moderate risk and one with high risk of bias. Overall, F-FDG PET scanning does not appear to consistently identify endometriotic lesions, and therefore its reliability and usefulness in endometriosis diagnosis is limited. The utility of Ga-DOTATATE PET-CT remains uncertain. Findings are constrained by limited available evidence reporting outcomes of PET imaging for endometriosis. Other existing PET tracers with biological plausibility in the detection or monitoring of endometriosis warrant further investigation.
PubMed: 38917749
DOI: 10.1016/j.ejogrb.2024.06.017 -
Radiography (London, England : 1995) Jun 2024Artificial intelligence (AI) in positron emission tomography/computed tomography (PET/CT) can be used to improve image quality when it is useful to reduce the injected...
PURPOSE
Artificial intelligence (AI) in positron emission tomography/computed tomography (PET/CT) can be used to improve image quality when it is useful to reduce the injected activity or the acquisition time. Particular attention must be paid to ensure that users adopt this technological innovation when outcomes can be improved by its use. The aim of this study was to identify the aspects that need to be analysed and discussed to implement an AI denoising PET/CT algorithm in clinical practice, based on the representations of Nuclear Medicine Technologists (NMT) from Western-Switzerland, highlighting the barriers and facilitators associated.
METHODS
Two focus groups were organised in June and September 2023, involving ten voluntary participants recruited from all types of medical imaging departments, forming a diverse sample of NMT. The interview guide followed the first stage of the revised model of Ottawa of Research Use. A content analysis was performed following the three-stage approach described by Wanlin. Ethics cleared the study.
RESULTS
Clinical practice, workload, knowledge and resources were de 4 themes identified as necessary to be thought before implementing an AI denoising PET/CT algorithm by ten NMT participants (aged 31-60), not familiar with this AI tool. The main barriers to implement this algorithm included workflow challenges, resistance from professionals and lack of education; while the main facilitators were explanations and the availability of support to ask questions such as a "local champion".
CONCLUSION
To implement a denoising algorithm in PET/CT, several aspects of clinical practice need to be thought to reduce the barriers to its implementation such as the procedures, the workload and the available resources. Participants emphasised also the importance of clear explanations, education, and support for successful implementation.
IMPLICATIONS FOR PRACTICE
To facilitate the implementation of AI tools in clinical practice, it is important to identify the barriers and propose strategies that can mitigate it.
PubMed: 38917681
DOI: 10.1016/j.radi.2024.06.010 -
Applied Radiation and Isotopes :... Jun 2024This study aimed to determine the optimal injection dose for non-human primate positron emission tomography (PET). We first used a monkey brain phantom with a volume of...
This study aimed to determine the optimal injection dose for non-human primate positron emission tomography (PET). We first used a monkey brain phantom with a volume of 80,000 mm containing 250 MBq of [F]FDG. Next, we compared the radioactivity difference between the PET images and the actual radioactivity from the dose calibrator to determine the low-error range. We then evaluated the image quality using the NEMA-NU phantom. Finally, [F]FP-CIT PET images were obtained from two monkeys with middle and high doses. As a result, PET images with a middle injected dose generated reasonable image quality and showed a high signal-to-noise ratio in monkey brain PET with [F]FP-CIT. These results are expected to be actively applied in PET research using non-human primates.
PubMed: 38917619
DOI: 10.1016/j.apradiso.2024.111404 -
European Journal of Endocrinology Jun 2024Brown adipose tissue (BAT) is a therapeutic target for obesity. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is commonly used to quantify human BAT...
OBJECTIVE
Brown adipose tissue (BAT) is a therapeutic target for obesity. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is commonly used to quantify human BAT mass and activity. Detectable 18F-FDG uptake by BAT is associated with reduced prevalence of cardiometabolic disease. However, 18F-FDG uptake may not always be a reliable marker of BAT thermogenesis, for example insulin resistance may reduce glucose uptake. Uncoupling protein 1 (UCP1) is the key thermogenic protein in BAT. Therefore, we hypothesized that UCP1 expression may be altered in individuals with cardiometabolic risk factors.
METHODS
We quantified UCP1 expression as an alternative marker of thermogenic capacity in BAT and white adipose tissue (WAT) samples (n = 53) and in differentiated brown and white pre-adipocytes (n = 85).
RESULTS
UCP1 expression in BAT, but not in WAT or brown/white differentiated pre-adipocytes, was reduced with increasing age, obesity and adverse cardiometabolic risk factors such as fasting glucose, insulin and blood pressure. However, UCP1 expression in BAT was preserved in obese subjects of <40 years of age. To determine if BAT activity was also preserved in vivo, we undertook a case-control study, performing 18F-FDG scanning during mild cold exposure in young (mean age ∼22y) normal weight and obese volunteers. 18F-FDG uptake by BAT and BAT volume were similar between groups, despite increased insulin resistance.
CONCLUSION
18F-FDG uptake by BAT and UCP1 expression are preserved in young obese adults. Older subjects retain precursor cells with the capacity to form new thermogenic adipocytes. These data highlight the therapeutic potential of BAT mass expansion and activation in obesity.
PubMed: 38917410
DOI: 10.1093/ejendo/lvae074 -
Giornale Italiano Di Cardiologia (2006) Jul 2024Lymphoma patients are at high risk of cardiovascular events due to anthracycline cardiotoxicity and, in rare cases, related to heart infiltration. The presence of...
Lymphoma patients are at high risk of cardiovascular events due to anthracycline cardiotoxicity and, in rare cases, related to heart infiltration. The presence of cardiac masses adds further complexity to the management of lymphoma patients beyond myocardial chemotherapy-related toxicity, given possible unpredictable acute complications such as arrhythmias, atrioventricular block, myocardial ischemia, pericardial effusion and cardiac tamponade. Here we describe the clinical presentation and successful multidisciplinary management of diffuse large B-cell lymphoma with multifocal cardiac involvement identified by total body 18FDG positron emission tomography performed at disease staging.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Heart Neoplasms; Positron-Emission Tomography; Fluorodeoxyglucose F18; Male; Radiopharmaceuticals; Middle Aged; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols; Female; Aged
PubMed: 38916468
DOI: 10.1714/4282.42640 -
Expert Review of Hematology Jun 2024Despite clear advancements in the management of classical Hodgkin lymphoma (cHL) over the past decade including better risk stratification, the usage of... (Review)
Review
INTRODUCTION
Despite clear advancements in the management of classical Hodgkin lymphoma (cHL) over the past decade including better risk stratification, the usage of 18F-flurodeoxyglucose positron emission tomography (FDG-PET) guided approaches and incorporation of novel agents, approximately one third of patients will relapse. Important themes have been recently explored in the first salvage setting including the recognition of the positive prognostic value of a negative pre-autologous stem cell transplantation (ASCT) FDG-PET response and the incorporation of novel agents such as brentuximab vedotin (BV) and immune checkpoint inhibitors (CPIs) as salvage regimens to improve patient outcomes.
AREAS COVERED
The evolving treatment paradigm in optimizing salvage therapy in relapsed refractory cHL (RR-cHL) is discussed, including a vision to the future. The methodology included a literature search on pubmed using keywords. Selected articles were screened and evaluated by the authors of this review.
EXPERT OPINION
Achieving a complete remission by FDG-PET pre-ASCT is the most important prognostic factor in obtaining disease control and subsequent cure, and therefore should be a key goal of any salvage regimen. Although data from randomized controlled trials are currently lacking, retrospective evidence demonstrate superior event free survival with CPI-based regimens compared to conventional chemotherapy or BV based therapy.
PubMed: 38916254
DOI: 10.1080/17474086.2024.2372325 -
Frontiers in Medicine 2024Immunotherapy targeted to immune checkpoint inhibitors, such as the program cell death receptor (PD-1) and its ligand (PD-L1), has revolutionized cancer treatment.... (Review)
Review
Immunotherapy targeted to immune checkpoint inhibitors, such as the program cell death receptor (PD-1) and its ligand (PD-L1), has revolutionized cancer treatment. However, it is now well-known that PD-1/PD-L1 immunotherapy response is inconsistent among patients. The current challenge is to customize treatment regimens per patient, which could be possible if the PD-1/PD-L1 expression and dynamic landscape are known. With positron emission tomography (PET) imaging, it is possible to image these immune targets non-invasively and system-wide during therapy. A successful PET imaging tracer should meet specific criteria concerning target affinity, specificity, clearance rate and target-specific uptake, to name a few. The structural profile of such a tracer will define its properties and can be used to optimize tracers in development and design new ones. Currently, a range of PD-1/PD-L1-targeting PET tracers are available from different molecular categories that have shown impressive preclinical and clinical results, each with its own advantages and disadvantages. This review will provide an overview of current PET tracers targeting the PD-1/PD-L1 axis. Antibody, peptide, and antibody fragment tracers will be discussed with respect to their molecular characteristics and binding properties and ways to optimize them.
PubMed: 38915766
DOI: 10.3389/fmed.2024.1401515