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Journal of Clinical Medicine May 2024: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented....
: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented. Thus, our research aimed to explore the potential impact of various TKIs of GLUT-1 on the standard [F]FDG-PET monitoring of tumor response in patients. : To achieve this, we conducted an analysis on three patients who were undergoing treatment with different TKIs and harbored actionable alterations. Alongside the assessment of FDG data (including SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV)), we also examined the changes in tumor sizes through follow-up [F]FDG-PET/CT imaging. Notably, our patients harbored alterations in BRAFV600, RET, and c-KIT and exhibited positive responses to the targeted treatment. : Our analysis revealed that FDG data derived from SUVmax, TLG, and MTV offered quantifiable outcomes that were consistent with the measurements of tumor size. : These findings lend support to the notion that the inhibition of GLUT-1, as a consequence of treatment efficacy, could be indirectly gauged through [F] FDG-PET/CT imaging in cancer patients undergoing TKI therapy.
PubMed: 38892979
DOI: 10.3390/jcm13113269 -
International Journal of Molecular... May 2024One aspect of ovarian tumorigenesis which is still poorly understood is the tumor-stroma interaction, which plays a major role in chemoresistance and tumor progression....
One aspect of ovarian tumorigenesis which is still poorly understood is the tumor-stroma interaction, which plays a major role in chemoresistance and tumor progression. Cancer-associated fibroblasts (CAFs), the most abundant stromal cell type in the tumor microenvironment, influence tumor growth, metabolism, metastasis, and response to therapy, making them attractive targets for anti-cancer treatment. Unraveling the mechanisms involved in CAFs activation and maintenance is therefore crucial for the improvement of therapy efficacy. Here, we report that CAFs phenoconversion relies on the glucose-dependent inhibition of autophagy. We show that ovarian cancer cell-conditioning medium induces a metabolic reprogramming towards the CAF-phenotype that requires the autophagy-dependent glycolytic shift. In fact, 2-deoxy-D-glucose (2DG) strongly hampers such phenoconversion and, most importantly, induces the phenoreversion of CAFs into quiescent fibroblasts. Moreover, pharmacological inhibition (by proline) or autophagy gene knockdown (by siBECN1 or siATG7) promotes, while autophagy induction (by either 2DG or rapamycin) counteracts, the metabolic rewiring induced by the ovarian cancer cell secretome. Notably, the nutraceutical resveratrol (RV), known to inhibit glucose metabolism and to induce autophagy, promotes the phenoreversion of CAFs into normal fibroblasts even in the presence of ovarian cancer cell-conditioning medium. Overall, our data support the view of testing autophagy inducers for targeting the tumor-promoting stroma as an adjuvant strategy to improve therapy success rates, especially for tumors with a highly desmoplastic stroma, like ovarian cancer.
Topics: Humans; Female; Autophagy; Cancer-Associated Fibroblasts; Ovarian Neoplasms; Glucose; Cell Line, Tumor; Tumor Microenvironment; Resveratrol; Culture Media, Conditioned; Deoxyglucose; Glycolysis
PubMed: 38891879
DOI: 10.3390/ijms25115691 -
Radiology Jun 2024Background Human epidermal growth factor receptor 2 (HER2) affibody-based tracers could be an alternative to nonspecific radiotracers for noninvasive detection of HER2... (Comparative Study)
Comparative Study
Background Human epidermal growth factor receptor 2 (HER2) affibody-based tracers could be an alternative to nonspecific radiotracers for noninvasive detection of HER2 expression in breast cancer lesions at PET/CT. Purpose To compare an affibody-based tracer, AlF-NOTA-HER2-BCH, and fluorine 18 (F) fluorodeoxyglucose (FDG) for detecting HER2-positive breast cancer lesions on PET/CT images. Materials and Methods In this prospective study conducted from June 2020 to July 2023, participants with HER2-positive breast cancer underwent both AlF-NOTA-HER2-BCH and F-FDG PET/CT. HER2 positivity was confirmed with pathologic assessment (immunohistochemistry test results of 3+, or 2+ followed by fluorescence in situ hybridization, indicated HER2 amplification). Two independent readers visually assessed the uptake of tracers on images. Lesion uptake was quantified using the maximum standardized uptake value (SUV) and target to background ratio (TBR) and compared using a general linear mixed model. Results A total of 42 participants (mean age, 56.3 years ± 10.1 [SD]; 41 female) with HER2-positive breast cancer were included; 42 (100%) had tumors that were detected with AlF-NOTA-HER2-BCH PET/CT and 40 (95.2%) had tumors detected with F-FDG PET/CT. Primary tumors in two of 21 participants, lymph node metastases in four of 21 participants, bone metastases in four of 15 participants, and liver metastases in three of nine participants were visualized only with AlF-NOTA-HER2-BCH. Lung metastasis in one of nine participants was visualized only with F-FDG. AlF-NOTA-HER2-BCH enabled depiction of more suspected HER2-positive primary tumors (26 vs 21) and lymph node (170 vs 130), bone (92 vs 66), and liver (55 vs 27) metastases than F-FDG. The SUV and TBR values of primary tumors and lymph node, bone, and liver metastases were all higher on AlF-NOTA-HER2-BCH images than on F-FDG images (median SUV range, 10.4-13.5 vs 3.4-6.2; value range, <.001 to .02; median TBR range, 2.7-17.6 vs 1.2-7.8; value range, <.001 to .001). No evidence of differences in the SUV and TBR for chest wall or lung metastases was observed between AlF-NOTA-HER2-BCH and F-FDG ( value range, .06 to .53). Conclusion PET/CT with the affibody-based tracer AlF-NOTA-HER2-BCH enabled detection of more primary lesions and lymph node, bone, and liver metastases than PET/CT using F-FDG. ClinicalTrials.gov Identifier: NCT04547309 © RSNA, 2024 See also the editorial by Ulaner in this issue.
Topics: Humans; Fluorodeoxyglucose F18; Female; Breast Neoplasms; Positron Emission Tomography Computed Tomography; Middle Aged; Receptor, ErbB-2; Prospective Studies; Radiopharmaceuticals; Aged; Adult; Recombinant Fusion Proteins
PubMed: 38888484
DOI: 10.1148/radiol.232209 -
Nuclear Medicine Review. Central &... 2024Muir-Torre syndrome (MTS) is a rare genetic disorder, considered a subtype of Lynch syndrome, that causes sebaceous cutaneous tumors and increases the risk of internal...
Muir-Torre syndrome (MTS) is a rare genetic disorder, considered a subtype of Lynch syndrome, that causes sebaceous cutaneous tumors and increases the risk of internal visceral tumors. We present a case of a 63-year-old male with a history of MTS with sebaceous tumors, colorectal, and urothelial cancers who underwent fluorine-18-deoxyglucose positron emission tomography/ computed tomography [18F]FDG PET/CT to follow-up on multiple [18F]FDG avid skin lesions and right pelvic lymph nodes. Although few reports are available detailing the utility of [18F]FDG PET/CT in this rare disease, this modality appears useful, and superior, to computed tomography in the diagnosis and follow-up of MTS.
Topics: Humans; Fluorodeoxyglucose F18; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Muir-Torre Syndrome
PubMed: 38887062
DOI: 10.5603/nmr.99686 -
BMC Pulmonary Medicine Jun 2024The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of...
BACKGROUND
The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare.
CASE PRESENTATION
A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant F-FDG uptake on F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis.
CONCLUSION
Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.
Topics: Humans; Female; Middle Aged; Thymoma; Lymphocytosis; Pleural Neoplasms; Bone Neoplasms; Positron Emission Tomography Computed Tomography; Thymus Neoplasms; T-Lymphocytes; Fluorodeoxyglucose F18; Diagnosis, Differential; Pleura
PubMed: 38877486
DOI: 10.1186/s12890-024-03090-x -
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