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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 : Official... Jul 2024The integration of automated whole-body tumor segmentation using F-FDG PET/CT images represents a pivotal shift in oncologic diagnostics, enhancing the precision and...
The integration of automated whole-body tumor segmentation using F-FDG PET/CT images represents a pivotal shift in oncologic diagnostics, enhancing the precision and efficiency of tumor burden assessment. This editorial examines the transition toward automation, propelled by advancements in artificial intelligence, notably through deep learning techniques. We highlight the current availability of commercial tools and the academic efforts that have set the stage for these developments. Further, we comment on the challenges of data diversity, validation needs, and regulatory barriers. The role of metabolic tumor volume and total lesion glycolysis as vital metrics in cancer management underscores the significance of this evaluation. Despite promising progress, we call for increased collaboration across academia, clinical users, and industry to better realize the clinical benefits of automated segmentation, thus helping to streamline workflows and improve patient outcomes in oncology.
Topics: Humans; Fluorodeoxyglucose F18; Whole Body Imaging; Image Processing, Computer-Assisted; Neoplasms; Positron Emission Tomography Computed Tomography; Automation
PubMed: 38844359
DOI: 10.2967/jnumed.123.267183 -
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 -
Biomedicine & Pharmacotherapy =... Jul 2024Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic...
Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic switching is a hallmark of cancer cells that facilitates metastasis. Cancer cells obtain most of their energy and intermediate metabolites, which are required to proliferate and metastasize, through aerobic glycolysis. Previous work from our laboratory has shown that Caveolin-1 (CAV1) expression in cancer cells promotes glycolysis and metastasis. Here, we sought to determine if limiting glycolysis reduced CAV1-enhanced metastasis and to identify the mechanism(s) involved. We evaluated the effects of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) in metastatic melanoma and breast cancer cell lines expressing or not CAV1. Non-cytotoxic concentrations of 2-DG (1 mM) inhibited the migration of B16-F10 melanoma and MDA-MB-231 breast cancer cells. CAV1-mediated activation of Src/Akt signaling was required for CAV1-enhanced migration and was blocked in the presence of 2-DG. Moreover, inhibition of Akt reduced CAV1-enhanced lung metastasis of B16-F10 cells. Collectively, these findings highlight the importance of CAV1-induced metabolic reprogramming for metastasis and point towards possible therapeutic approaches to prevent metastatic disease by inhibiting glycolysis and Src/Akt signaling.
Topics: Caveolin 1; Glycolysis; Proto-Oncogene Proteins c-akt; Animals; Signal Transduction; src-Family Kinases; Humans; Cell Line, Tumor; Mice; Cell Movement; Deoxyglucose; Female; Neoplasm Metastasis; Melanoma, Experimental; Breast Neoplasms; Lung Neoplasms; Mice, Inbred C57BL
PubMed: 38834004
DOI: 10.1016/j.biopha.2024.116841 -
Clinical Imaging Aug 2024This meta-analysis aimed to compare the diagnostic effectiveness of [F]FDG PET/CT with that of [F]FDG PET/MRI in terms of identifying liver metastasis in patients with... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
This meta-analysis aimed to compare the diagnostic effectiveness of [F]FDG PET/CT with that of [F]FDG PET/MRI in terms of identifying liver metastasis in patients with primary cancer.
METHODS
PubMed, Embase, Web of Science, and the Cochrane Library were searched, and studies evaluating the diagnostic efficacy of [F]FDG PET/CT and [F]FDG PET/MRI in patients with liver metastasis of primary cancer were included. We used a random effects model to analyze their sensitivity and specificity. Subgroup analyses and corresponding meta-regressions focusing on race, image analysis, study design, and analysis methodologies were conducted. Cochrane Q and I statistics were used to assess intra-group and inter-group heterogeneity.
RESULTS
Seven articles with 343 patients were included in this meta-analysis. The sensitivity of [F]FDG PET/CT was 0.82 (95 % CI: 0.63-0.96), and that of [F]FDG PET/MRI was 0.91 (95 % CI: 0.82-0.98); there was no significant difference between the two methods (P = 0.32). Similarly, both methods showed equal specificity: 1.00 (95 % CI: 0.95-1.00) for [F]FDG PET/CT and 1.00 (95 % CI: 0.96-1.00) for [F]FDG PET/MRI, and thus, there was no significant difference between the methods (P = 0.41). Furthermore, the subgroup analyses revealed no differences. Meta-regression analysis revealed that race was a potential source of heterogeneity for [F]FDG PET/CT (P = 0.01), while image analysis and contrast agent were found to be potential sources of heterogeneity for [18F]FDG PET/MRI (P = 0.02).
CONCLUSIONS
[F]FDG PET/MRI has similar sensitivity and specificity to [F]FDG PET/CT for detecting liver metastasis of primary cancer in both the general population and in subgroups. [F]FDG PET/CT may be a more cost-effective option. However, the conclusions of this meta-analysis are tentative due to the limited number of studies included, and further research is necessary for validation.
Topics: Humans; Fluorodeoxyglucose F18; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Multimodal Imaging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 38833916
DOI: 10.1016/j.clinimag.2024.110209 -
Cancer Imaging : the Official... Jun 2024This study investigates the value of fluorine 18 ([F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage...
BACKGROUND
This study investigates the value of fluorine 18 ([F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC).
METHODS
From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [F]-fluorodeoxyglucose (FDG) and [F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [F]FDG and [F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated.
RESULTS
In 53 patients (median age, 64 years, range: 31-76 years), the specificity of [F]FAPI for detecting LN metastasis was significantly higher than that of [F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUV (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [F]FAPI in this circumstance improved the diagnostic value. LNs with an [F]FAPI SUV<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [F]FAPI SUV≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [F]FDG and [F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients.
CONCLUSION
In patients with stage I-IIIA NSCLC, [F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [F]FDG PET/CT. Integrating [F]FDG and [F]FAPI PET/CT resulted in more precise clinical decisions.
TRIAL REGISTRATION
The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995 ).
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Middle Aged; Male; Female; Lung Neoplasms; Prospective Studies; Fluorodeoxyglucose F18; Aged; Positron Emission Tomography Computed Tomography; Adult; Lymphatic Metastasis; Radiopharmaceuticals; Neoplasm Staging; Lymph Nodes
PubMed: 38831354
DOI: 10.1186/s40644-024-00701-y