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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 -
BMC Cancer Jun 2024The axillary lymph-node metastatic burden is closely associated with treatment decisions and prognosis in breast cancer patients. This study aimed to explore the value...
BACKGROUND
The axillary lymph-node metastatic burden is closely associated with treatment decisions and prognosis in breast cancer patients. This study aimed to explore the value of F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT)-based radiomics in combination with ultrasound and clinical pathological features for predicting axillary lymph-node metastatic burden in breast cancer.
METHODS
A retrospective analysis was conducted and involved 124 patients with pathologically confirmed early-stage breast cancer who had undergone F-FDG PET/CT examination. The ultrasound, PET/CT, and clinical pathological features of all patients were analysed, and radiomic features from PET images were extracted to establish a multi-parameter predictive model.
RESULTS
The ultrasound lymph-node positivity rate and PET lymph-node positivity rate in the high nodal burden group were significantly higher than those in the low nodal burden group (χ = 19.867, p < 0.001; χ = 33.025, p < 0.001). There was a statistically significant difference in the PET-based radiomics score (RS) for predicting axillary lymph-node burden between the high and low lymph-node burden groups. (-1.04 ± 0.41 vs. -1.47 ± 0.41, t = -4.775, p < 0.001). The ultrasound lymph-node positivity (US_LNM) (odds ratio [OR] = 3.264, 95% confidence interval [CI] = 1.022-10.423), PET lymph-node positivity (PET_LNM) (OR = 14.242, 95% CI = 2.960-68.524), and RS (OR = 5.244, 95% CI = 3.16-20.896) are all independent factors associated with high lymph-node burden (p < 0.05). The area under the curve (AUC) of the multi-parameter (MultiP) model was 0.895, which was superior to those of US_LNM, PET_LNM, and RS models (AUC = 0.703, 0.814, 0.773, respectively), with statistically significant differences (Z = 2.888, 3.208, 3.804, respectively; p = 0.004, 0.002, < 0.001, respectively). Decision curve analysis indicated that the MultiP model provided a higher net benefit for all patients.
CONCLUSION
A MultiP model based on PET-based radiomics was able to effectively predict axillary lymph-node metastatic burden in breast cancer.
TRIAL REGISTRATION
This study was registered with ClinicalTrials.gov (registration number: NCT05826197) on May 7, 2023.
Topics: Humans; Female; Breast Neoplasms; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Middle Aged; Lymphatic Metastasis; Retrospective Studies; Axilla; Adult; Aged; Lymph Nodes; Radiopharmaceuticals; Prognosis; Neoplasm Staging; Radiomics
PubMed: 38849770
DOI: 10.1186/s12885-024-12476-3 -
BMC Cancer Jun 2024[F]Fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [F]FDG PET has several inherent...
BACKGROUND
[F]Fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [Ga]Ga-FAPI-46 PET/CT and [F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.
METHODS AND DESIGN
Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [F]FDG PET/CT). Study subjects in Group B will undergo an additional [Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.
DISCUSSION
To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.
TRIAL REGISTRATION
clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.
Topics: Humans; Female; Positron Emission Tomography Computed Tomography; Ovarian Neoplasms; Prospective Studies; Neoplasm Staging; Fluorodeoxyglucose F18; Gallium Radioisotopes; Radiopharmaceuticals; Middle Aged; Adult; Aged; Quinolines
PubMed: 38849741
DOI: 10.1186/s12885-024-12461-w -
Journal of Nuclear Medicine Technology Jun 2024The esophagus is rarely affected by A 75-y-old man presented with upper abdominal pain and significant weight loss for 2 mo. Contrast-enhanced CT, upper...
The esophagus is rarely affected by A 75-y-old man presented with upper abdominal pain and significant weight loss for 2 mo. Contrast-enhanced CT, upper gastrointestinal endoscopy, and abdominal vessel angiography gave normal results. To clarify the facts, F-FDG PET/CT was performed, revealing an F-FDG-avid lesion in the posterior wall of the lower thoracic esophagus. On endoscopic ultrasound-guided fine-needle aspiration of this lesion, puslike material was released. On microscopic examination, acid-fast bacilli were noted. The patient then began receiving standard antitubercular therapy.
Topics: Humans; Male; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Aged; Abdominal Pain; Esophageal Diseases; Tuberculosis
PubMed: 38839125
DOI: 10.2967/jnmt.123.266428 -
Journal of Nuclear Medicine Technology Jun 2024In a 32-y-old man with neurofibromatosis type 1, F-FDG PET/CT incidentally revealed a vesicourachal diverticulum, a rare anatomic variant. The PET/CT, performed for...
In a 32-y-old man with neurofibromatosis type 1, F-FDG PET/CT incidentally revealed a vesicourachal diverticulum, a rare anatomic variant. The PET/CT, performed for staging a malignant peripheral nerve sheath tumor, highlighted a distinctive F-FDG-avid pattern crucial for accurate diagnosis. Recognizing such features enhances disease assessment and clarifies distinctions between benign urogenital anomalies and malignancies in F-FDG PET/CT staging.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Incidental Findings; Male; Adult; Diverticulum; Cell Transformation, Neoplastic; Neoplasm Staging; Neurofibromatosis 1; Urinary Bladder
PubMed: 38839116
DOI: 10.2967/jnmt.123.266570 -
Journal of Nuclear Medicine Technology Jun 2024Brown fat can present challenges in patients with cancer who undergo F-FDG PET scans. Uptake of F-FDG by brown fat can obscure or appear similar to active oncologic...
Brown fat can present challenges in patients with cancer who undergo F-FDG PET scans. Uptake of F-FDG by brown fat can obscure or appear similar to active oncologic lesions, causing clinical challenges in PET interpretation. Small, retrospective studies have reported environmental and pharmacologic interventions for suppressing brown fat uptake on PET; however, there is no clear consensus on best practices. We sought to characterize practice patterns for strategies to mitigate brown fat uptake of F-FDG during PET scanning. A survey was developed and distributed via e-mail LISTSERV to members of the Children's Oncology Group diagnostic imaging committee, the Society for Nuclear Medicine and Molecular Imaging pediatric imaging council, and the Society of Chiefs of Radiology at Children's Hospitals between April 2022 and February 2023. Responses were stored anonymously in REDCap, aggregated, and summarized using descriptive statistics. Fifty-five complete responses were submitted: 51 (93%) faculty and fellow-level physicians, 2 (4%) technologists, and 2 (4%) respondents not reporting their rank. There were 43 unique institutions represented, including 5 (12%) outside the United States. Thirty-eight of 41 (93%) institutions that responded on environmental interventions reported using warm blankets in the infusion and scanning rooms. Less than a third ( = 13, 30%) of institutions reported use of a pharmacologic intervention, with propranolol ( = 5, 38%) being most common, followed by fentanyl ( = 4, 31%), diazepam ( = 2, 15%), and diazepam plus propranolol ( = 2, 15%). Selection criteria for pharmacologic intervention varied, with the most common criterion being brown fat uptake on a prior scan ( = 6, 45%). Clinical practices to mitigate brown fat uptake on pediatric F-FDG PET vary widely. Simple environmental interventions including warm blankets or increasing the temperature of the injection and scanning rooms were not universally reported. Less than a third of institutions use pharmacologic agents for brown fat mitigation.
Topics: Fluorodeoxyglucose F18; Humans; Positron Emission Tomography Computed Tomography; Adipose Tissue, Brown; Hospitals, Pediatric; Surveys and Questionnaires; Internationality; Biological Transport; Child
PubMed: 38839114
DOI: 10.2967/jnmt.123.266536