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Science Advances Jun 2024In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity...
In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.
Topics: Positron Emission Tomography Computed Tomography; Animals; Single-Cell Analysis; Cell Tracking; Whole Body Imaging; Mice; Humans; Fluorodeoxyglucose F18; Cell Line, Tumor; Algorithms; Melanoma
PubMed: 38875333
DOI: 10.1126/sciadv.adk5747 -
Journal of Medical Imaging and... Jun 2024Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic...
18F-fluorodeoxyglucose PET-CT-guided pelvic chemoradiation therapy using helical tomotherapy for locally advanced carcinoma cervix without para-aortic nodal disease: Clinical and patient-reported outcomes from a prospective phase 2 study.
INTRODUCTION
Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic information from 18 fluro-deoxyglucose positron emission tomography combined with contrast-enhanced computerized tomography (FDG PET-CT) may potentially augment treatment decision-making for LACC. This study ascertained FDG-PET CT influence on chemoradiation therapy (CTRT) decisions in LACC. We report oncologic and patient-reported outcome measures (PROMs).
METHODS
FDG PET-CT scans were reviewed independently by two nuclear medicine specialists and two radiation oncologists. Pelvic CTRT plan digressions were documented and therapy was adapted accordingly. Pelvis radiation (50 Gy/25#/5 weeks) using tomotherapy with weekly cisplatin was used in node-negative disease. Dose-escalated simultaneous integrated boost (SIB) 60 Gy/25#/5 weeks was delivered to involved pelvic nodes. All received brachytherapy. Post-treatment PET-CT scans were at 6 months. Functional assessment of cancer therapy scores were calculated at baseline, treatment completion, 3 months, 1 year and 3 years.
RESULTS
Between November 2015 and January 2018, 85 patients were screened, and 77 consented. Extrapelvic disease was seen in 12 (16%) patients (9 para-aortic nodes, 2 distant metastases and 1 synchronous carcinoma breast); 60 patients were included in the final analysis. Decision changes were seen in 10/77 (13%) screened, 8/60 (13%) included and 32 (53.3%) received SIB. Post-treatment, 27 (45%) had grade 2 GI/GU/GYN toxicity, one (2%) had grade 3 GI and five (8.3%) had grade 3 neutropenia. At median overall survival of 54.2 months (95% CI 52.8-58.3), 5-year local failure, pelvic nodal and para-aortic nodal-free survival were 86.8% (95% CI 78.0-96.6), 85.2% (95% CI 76.1-95.3) and 85.2% (95% CI 76.2-95.4). Functional assessment of cancer therapy trial outcome index (FACT TOI) improved by 10.43 at 3 months with no further decline. Grade 3 toxicity was noted for abdominal pain in one (1.7%), cystitis in four (6.7%) and lymphoedema in one (1.7%) at 5 years.
CONCLUSION
PET-CT resulted in major decision changes in 13%. PET-adapted CTRT was associated with acceptable toxicity, encouraging long-term survival and improvement in PROMS.
PubMed: 38874192
DOI: 10.1111/1754-9485.13667 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024Cachexia-associated body composition alterations and tumor metabolic activity are both associated with survival of cancer patients. Recently, subcutaneous adipose tissue...
BACKGROUND
Cachexia-associated body composition alterations and tumor metabolic activity are both associated with survival of cancer patients. Recently, subcutaneous adipose tissue properties have emerged as particularly prognostic body composition features. We hypothesized that tumors with higher metabolic activity instigate cachexia related peripheral metabolic alterations, and investigated whether tumor metabolic activity is associated with body composition and survival in patients with non-small-cell lung cancer (NSCLC), focusing on subcutaneous adipose tissue.
METHODS
A retrospective analysis was performed on a cohort of 173 patients with NSCLC. F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans obtained before treatment were used to analyze tumor metabolic activity (standardized uptake value (SUV) and SUV normalized by lean body mass (SUL)) as well as body composition variables (subcutaneous and visceral adipose tissue radiodensity (SAT/VAT radiodensity) and area; skeletal muscle radiodensity (SM radiodensity) and area). Subjects were divided into groups with high or low SAT radiodensity based on Youden Index of Receiver Operator Characteristics (ROC). Associations between tumor metabolic activity, body composition variables, and survival were analyzed by Mann-Whitney tests, Cox regression, and Kaplan-Meier analysis.
RESULTS
The overall prevalence of high SAT radiodensity was 50.9% (88/173). Patients with high SAT radiodensity had shorter survival compared with patients with low SAT radiodensity (mean: 45.3 vs. 50.5 months, p = 0.026). High SAT radiodensity was independently associated with shorter overall survival (multivariate Cox regression HR = 1.061, 95% CI: 1.022-1.101, p = 0.002). SAT radiodensity also correlated with tumor metabolic activity (SULpeak r = 0.421, p = 0.029; SUVpeak r = 0.370, p = 0.048). In contrast, the cross-sectional areas of SM, SAT, and VAT were not associated with tumor metabolic activity or survival.
CONCLUSION
Higher SAT radiodensity is associated with higher tumor metabolic activity and shorter survival in patients with NSCLC. This may suggest that tumors with higher metabolic activity induce subcutaneous adipose tissue alterations such as decreased lipid density, increased fibrosis, or browning.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Male; Female; Retrospective Studies; Subcutaneous Fat; Lung Neoplasms; Aged; Positron Emission Tomography Computed Tomography; Middle Aged; Body Composition; Cachexia; Fluorodeoxyglucose F18; Prognosis
PubMed: 38870661
DOI: 10.1016/j.clnu.2024.05.040 -
Tuberkuloz Ve Toraks Jun 2024Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB...
Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB cases present as extrapulmonary TB. The diagnosis of extrapulmonary TB is often overlooked due to its atypical clinical and radiological manifestations. Differentiating TB from neoplastic conditions poses significant challenges. A 33-year-old female patient was admitted to the emergency clinic with shortness of breath, cough, and abdominal pain. Postero-anterior chest X-ray revealed massive pleural effusion leading to mediastinal shift. With a preliminary diagnosis of malignant pleural effusion, a pleural catheter was inserted, and the patient was referred for a positron emission tomography (PET/CT) to assess the primary site and the optimal location for a biopsy. The PET/CT revealed asymmetric soft tissue thickening on the left side of the nasopharynx, and increased fluorodeoxyglucose (FDG) uptake in the left cervical lymph nodes raised suspicion regarding primary nasopharyngeal cancer. Additionally, there was an increased FDG uptake observed in the mass lesion located in the right upper lobe, mediastinal lymph nodes, pleural surfaces in the left hemithorax, perihepatic areas, and peritoneum, indicating diffuse metastatic disease. Tuberculosis diagnosis was confirmed through biopsies demonstrating granulomatous inflammation in the lung and nasopharynx, along with culturing MTB from pleural effusion. Positron emission tomography played a crucial role in identifying sites of TB involvement. Despite its rarity, healthcare professionals should consider nasopharyngeal TB as a potential diagnosis when evaluating nasopharyngeal masses.
Topics: Humans; Female; Adult; Diagnosis, Differential; Positron Emission Tomography Computed Tomography; Tuberculosis; Fluorodeoxyglucose F18; Neoplasm Metastasis
PubMed: 38869209
DOI: 10.5578/tt.202402915 -
Breast Cancer Research and Treatment Aug 2024Breast cancer (BC) patients undergoing FDG-PET/CT scans for neoadjuvant chemotherapy (NAC) may have additional non-BC related findings. The aim of this study is to...
PURPOSE
Breast cancer (BC) patients undergoing FDG-PET/CT scans for neoadjuvant chemotherapy (NAC) may have additional non-BC related findings. The aim of this study is to describe the clinical implications of these findings.
METHODS
We included BC patients who underwent an FDG-PET/CT scan in our institute between 2011-2020 prior to NAC. We focused on patients with an additional non-BC related finding (i.e. BC metastases were excluded) for which diagnostic work-up was performed. Information about the diagnostic work-up and the clinical consequences was retrospectively gathered. A revision of all FDG-PET/CT scans was conducted by an independent physician to assess the suspicion level of the additional findings.
RESULTS
Of the 1337 patients who underwent FDG-PET/CT, 202 patients (15%) had an non-BC related additional finding for which diagnostic work-up was conducted, resulting in 318 examinations during the first year. The non-BC related findings were mostly detected in the endocrine region (26%), gastro-intestinal region (16%), or the lungs (15%). Seventeen patients (17/202: 8%, 17/1337: 1.3%) had a second primary malignancy. Only 8 patients (8/202: 4%, 8/1337: 0.6%) had a finding that was considered more prognosis-determining than their BC disease. When revising all FDG-PET/CT scans, 57 (202/57: 28%) of the patients had an additional finding categorized as low suspicious, suggesting no indication for diagnostic work-up.
CONCLUSION
FDG-PET/CT scans used for dissemination imaging in BC patients detect a high number of non-BC related additional findings, often clinically irrelevant and causing a large amount of unnecessary work-up. However, in 8% of the patients undergoing diagnostic work-up for an additional finding, a second primary malignancy was detected, warranting diagnostic attention in selected patients.
Topics: Humans; Female; Breast Neoplasms; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Neoadjuvant Therapy; Middle Aged; Retrospective Studies; Aged; Adult; Radiopharmaceuticals; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38864980
DOI: 10.1007/s10549-024-07331-9 -
Cancer Imaging : the Official... Jun 2024Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the...
BACKGROUND
Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB.
METHODS
We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC).
RESULTS
During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS.
CONCLUSION
WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.
Topics: Humans; Neuroblastoma; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Male; Female; Retrospective Studies; Prognosis; Child, Preschool; Child; Infant; Radiopharmaceuticals; Adolescent; Tumor Burden
PubMed: 38863073
DOI: 10.1186/s40644-024-00718-3 -
Journal of Translational Medicine Jun 2024The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its...
PURPOSE
The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[F]fluoro-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) parameters.
METHODS
The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription‑quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated.
RESULTS
In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUV was an independent predictor of BATF expression. With 15.96 g/cm as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854.
CONCLUSION
BATF may be an oncogene associated with F-FDG PET/CT parameters in CRC. SUV may be an independent predictor of BATF expression.
Topics: Humans; Fluorodeoxyglucose F18; Colorectal Neoplasms; Basic-Leucine Zipper Transcription Factors; Positron Emission Tomography Computed Tomography; Female; Male; Disease Progression; Cell Proliferation; Cell Line, Tumor; Middle Aged; Gene Expression Regulation, Neoplastic; Glucose Transporter Type 1; Aged
PubMed: 38862971
DOI: 10.1186/s12967-024-05367-5 -
Journal of Cellular Biochemistry Jun 2024The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via...
The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.
PubMed: 38860522
DOI: 10.1002/jcb.30613 -
The Quarterly Journal of Nuclear... Jun 2024F-fluorodeoxyglucose (F-FDG) positron-emission tomography/computed tomography (PET/CT) as an imaging modality for the whole body has shown its value in detecting...
BACKGROUND
F-fluorodeoxyglucose (F-FDG) positron-emission tomography/computed tomography (PET/CT) as an imaging modality for the whole body has shown its value in detecting incidental colorectal adenoma. In clinical practice, adenomatous polyps can be divided into three groups: low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and cancer, which can lead to different clinical management. However, the relationship between the
18 F-FDG PET/CT SUVmax and the histological grade of adenomatous polyps is still not established, which is a challenging but valuable task.METHODS
This retrospective study included 255 patients with colorectal adenoma (CRA) or colorectal adenocarcinomas (AC) who had corresponding F-FDG uptake incidentally found on PET/CT. The correlations of SUV
max with pathological characteristics and tumor size were assessed. Neoplasms were divided into LGIN, HGIN, and AC according to histological grade. Receiver operating characteristic (ROC) analysis was applied to evaluate the predictive value of the SUVmax -only model and comprehensive models which were established with imaging and clinical predictors identified by univariate and multivariate analysis.RESULTS
The SUV
max was positively correlated with histological grades (r=0.529, P<0.001). Univariate and multivariate analysis showed that SUVmax was an independent risk factor among all groups except between HGIN and AC. The area under the curves (AUCs) of the comprehensive model for distinguishing between AC and adenoma, LGIN and HIGN, LGIN and AC, and HGIN and AC were 0.886, 0.780, 0.945, 0.733, respectively, which is statistically higher than the AUCs of the SUVmax -only model with 0.812, 0.733, 0.863, and 0.688, respectively.CONCLUSIONS
As an independent risk factor, SUV
max based on F-FDG PET/CT is highly associated with the histological grade of CRA. Thus, F-FDG PET/CT can serve as a noninvasive tool for precise diagnosis and assist in the preoperative formulation of treatment strategies for patients with incidental CRA.Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Male; Colorectal Neoplasms; Female; Middle Aged; Aged; Adenoma; Incidental Findings; Retrospective Studies; Adult; Neoplasm Grading; Aged, 80 and over; Predictive Value of Tests
PubMed: 38860275
DOI: 10.23736/S1824-4785.24.03554-4 -
Theranostics 2024The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the...
The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the injury site in the brain is currently limited. Delivering drugs to neurons presents an even more formidable challenge due to their lower numbers and less phagocytic nature compared to other brain cells. Additionally, the diverse types of neurons, each performing specific functions, necessitate precise targeting of those implicated in the disease. Moreover, the complex synthetic design of drug delivery systems often hinders their clinical translation. The production of nanomaterials at an industrial scale with high reproducibility and purity is particularly challenging. However, overcoming this challenge is possible by designing nanomaterials through a straightforward, facile, and easily reproducible synthetic process. In this study, we have developed a third-generation 2-deoxy-glucose functionalized mixed layer dendrimer () utilizing biocompatible and cost-effective materials a highly facile convergent approach, employing copper-catalyzed click chemistry. We further evaluated the systemic neuronal targeting and biodistribution of , and brain delivery of a neuroprotective agent pioglitazone () in a pediatric traumatic brain injury (TBI) model. The exhibits favorable characteristics including high water solubility, biocompatibility, biological stability, nanoscale size, and a substantial number of end groups suitable for drug conjugation. Upon systemic administration in a pediatric mouse model of traumatic brain injury (TBI), the localizes in neurons at the injured brain site, clears rapidly from off-target locations, effectively delivers , ameliorates neuroinflammation, and improves behavioral outcomes. The promising results coupled with a convenient synthetic approach for the construction of makes it a potential nanoplatform for addressing brain diseases.
Topics: Animals; Dendrimers; Neurons; Drug Delivery Systems; Deoxyglucose; Neuroprotective Agents; Mice; Pioglitazone; Blood-Brain Barrier; Brain Injuries, Traumatic; Brain; Brain Diseases; Humans; Disease Models, Animal; Tissue Distribution; Male
PubMed: 38855177
DOI: 10.7150/thno.95476