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Keywords = total metabolic tumor volume

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19 pages, 2456 KiB  
Article
Subtherapeutic Dose of Ionizing Radiation Reprograms the Pre-Metastatic Lung Niche, Accelerating Its Formation and Promoting Metastasis
by Paula de Oliveira, Inês Sofia Vala, Pedro Faísca, Joao C Guimaraes, Filomena Pina, Esmeralda Poli, Isabel Diegues, Hugo Osório, Rune Matthiesen, Karine Serre and Susana Constantino Rosa Santos
Int. J. Mol. Sci. 2025, 26(13), 6145; https://doi.org/10.3390/ijms26136145 - 26 Jun 2025
Viewed by 425
Abstract
Pre-metastatic niche (PMN) formation is a critical step in metastatic progression. However, the biological effects of subtherapeutic doses of ionizing radiation (SDIRs) following radiotherapy on this process remain unclear. Using a 4T1 breast cancer mouse model, we investigated the effects of SDIRs (3 [...] Read more.
Pre-metastatic niche (PMN) formation is a critical step in metastatic progression. However, the biological effects of subtherapeutic doses of ionizing radiation (SDIRs) following radiotherapy on this process remain unclear. Using a 4T1 breast cancer mouse model, we investigated the effects of SDIRs (3 × 0.3 Gy) on lung PMN development and metastasis upon SDIR exposure on days 8–10 post-tumor injection, followed by mastectomy and analyzed on day 24. SDIRs significantly increased the total metastatic volume (TMV) in lungs, suggesting an accelerated PMN formation. Mechanistically, the SDIR acted as an early catalyst for niche priming, upregulating Bv8 expression, enhancing neutrophil recruitment, and increasing MMP9, S100A8, and Il6 production in the PMN by day 11. Moreover, SDIR drives metastasis through distinct mechanisms. Proteomic analysis revealed SDIR-driven metabolic reprogramming, with a shift away from fatty acid metabolism toward glycolysis and lipid accumulation within the PMN. This shift contributes to extracellular matrix (ECM) remodeling, immune modulation, and the upregulation of adhesion-related pathways, shaping a microenvironment that accelerates metastatic outgrowth. By reprogramming the pre-metastatic lung, the SDIR highlights the need to integrate organ-specific radiation exposure into metastasis models. Metabolic and immune-stromal pathways emerge as potential therapeutic targets, underscoring the importance of refining radiotherapy strategies to mitigate unintended pro-metastatic effects. Full article
(This article belongs to the Special Issue New Insight into Radiation Biology and Radiation Exposure)
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18 pages, 2660 KiB  
Article
The Biochemical–Imaging Connection: Urinary Noradrenaline and Fluorodeoxyglucose-Positron Emission Tomography in Unresectable or Metastatic Pheochromocytomas and Paragangliomas
by Junki Takenaka, Shiro Watanabe, Takashige Abe, Satoshi Takeuchi, Kenji Hirata, Rina Kimura, Hiroshi Ishii, Naoto Wakabayashi, Mungunkhuyag Majigsuren and Kohsuke Kudo
Diagnostics 2025, 15(11), 1305; https://doi.org/10.3390/diagnostics15111305 - 22 May 2025
Viewed by 585
Abstract
Background/Objectives: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of neural crest origin that secrete varying levels of catecholamines. [18F]Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable tool for the detection of metastases and the prediction of prognoses. However, varying FDG avidities [...] Read more.
Background/Objectives: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of neural crest origin that secrete varying levels of catecholamines. [18F]Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable tool for the detection of metastases and the prediction of prognoses. However, varying FDG avidities in PPGLs raise concerns regarding cost-effectiveness and unnecessary radiation exposure. Catecholamine secretion patterns are associated with metastasis and clinical outcomes. This study aimed to explore the relationships among FDG avidity, catecholamine levels, and clinical factors in patients with PPGLs. Methods: This retrospective study included 25 patients with unresectable or metastatic PPGLs scheduled for [131I]metaiodobenzylguanidine therapy with FDG-PET data available within 40 days of urine catecholamine measurements. FDG avidity was assessed using semiquantitative parameters such as the maximum standardized uptake value (SUVmax), total metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Urine catecholamine levels were quantified. Logistic regression and Spearman’s correlation were performed to evaluate the relationship between FDG parameters and urinary catecholamine levels. Results: Urinary noradrenaline levels were significantly higher in patients with FDG-avid lesions than in those without (726.25 μg/day vs. 166.3 μg/day, p = 0.001). Noradrenaline levels showed significant positive correlations with SUVmax, MTV, and TLG (ρ = 0.527, 0.541, and 0.557, respectively; all p < 0.01). Urinary noradrenaline levels predicted FDG avidity with an AUC of 0.849; a cutoff value of 647.5 μg/day achieved 55.6% sensitivity and 100% specificity. Conclusions: Urinary noradrenaline levels were significantly associated with FDG avidity in PPGLs, suggesting their potential utility in predicting FDG-PET outcomes. Therefore, FDG-PET may be unnecessary in PPGL patients with low urinary noradrenaline levels. These findings may help optimize imaging strategies for patients with PPGLs. Full article
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13 pages, 891 KiB  
Article
The Role of [18F]FDG PET/CT Prior to and During Neoadjuvant Chemotherapy for Soft Tissue Sarcomas
by Stijn J.C. van der Burg, Bernies van der Hiel, Lotte Heimans, J. Martijn Kerst, Michel W.J.M. Wouters, Petur Snaebjornsson, Yvonne M. Schrage, Winette T.A. van der Graaf and Winan J. van Houdt
Curr. Oncol. 2025, 32(5), 257; https://doi.org/10.3390/curroncol32050257 - 28 Apr 2025
Viewed by 565
Abstract
This retrospective, single-center study investigates the association between PET parameters and pathological response or disease recurrence in patients with soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy (NACT). The maximum standardized uptake value (SUVmaxBL), metabolic tumor volume (MTVBL), and [...] Read more.
This retrospective, single-center study investigates the association between PET parameters and pathological response or disease recurrence in patients with soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy (NACT). The maximum standardized uptake value (SUVmaxBL), metabolic tumor volume (MTVBL), and total lesion glycolysis (TLGBL) were measured at baseline [18F]FDG PET/CT and the change in percentage (ΔSUVmax, ΔMTV, ΔTLG) from baseline to early evaluation [18F]FDG PET/CT was calculated. The optimal cutoff values of the different PET parameters for pathological response, defined as <10% residual viable tumor (RVT) or >15% fibrosis/hyalinization, and recurrence-free survival were obtained for analysis. Forty-two patients who underwent baseline [18F]FDG PET/CT and NACT followed by surgery were included between January 2015 and January 2023. The primary diagnoses were angiosarcoma (n = 15), leiomyosarcoma (n = 15), sarcoma not otherwise specified (n = 9) and synovial sarcoma (n = 3). Twenty-eight (66.6%) patients underwent an early evaluation PET/CT. MTVBL, TLGBL, and ΔSUVmax (p = 0.024; p = 0.042, p = 0.009, respectively) values above the cutoff were associated with a pathological response based on RVT. ΔSUVmax, ΔMTV, and ΔTLG (p = 0.002; p = 0.019; p = 0.039, respectively) values above the cutoff were positively related to >15% fibrosis/hyalinization. MTVBL, TLGBL, and ΔMTV (p = 0.014; p = 0.022; p = 0.034, respectively) values above the cutoff were prognostic for the recurrence of disease. [18F]FDG PET/CT has a promising role in STS patients treated with NACT. Full article
(This article belongs to the Special Issue Sarcoma Surgeries: Oncological Outcomes and Prognostic Factors)
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12 pages, 1953 KiB  
Article
[68Ga]-DOTATOC PET/CT Volumetric Parameters Reflect Metastatic Potential in Pancreatic Neuroendocrine Tumors
by So Jeong Kim, Jongtae Cha, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Si Young Song, Arthur Cho and Jung Hyun Jo
Cancers 2025, 17(9), 1487; https://doi.org/10.3390/cancers17091487 - 28 Apr 2025
Viewed by 504
Abstract
Background: [68Ga]-DOTATOC PET/CT is a valuable technique for identifying neuroendocrine tumors overexpressing somatostatin receptors; however, its diagnostic and prognostic utility for WHO low-grade pancreatic neuroendocrine tumors remains unclear. Therefore, we aimed to evaluate [68Ga]-DOTATOC uptake in well-differentiated pancreatic neuroendocrine [...] Read more.
Background: [68Ga]-DOTATOC PET/CT is a valuable technique for identifying neuroendocrine tumors overexpressing somatostatin receptors; however, its diagnostic and prognostic utility for WHO low-grade pancreatic neuroendocrine tumors remains unclear. Therefore, we aimed to evaluate [68Ga]-DOTATOC uptake in well-differentiated pancreatic neuroendocrine tumors and determine its predictive capability for metastasis. Methods: Patients with pathologically diagnosed well-differentiated, non-functional pancreatic neuroendocrine tumors who underwent [68Ga]-DOTATOC PET/CT between 2015 and 2021 were included. Medical records and [68Ga]-DOTATOC PET/CT indices (maximal and mean standardized uptake values, somatostatin receptor-expressing tumor volume, and total lesion somatostatin receptor expression in pancreatic tumors) were retrospectively reviewed. Correlations between indices were analyzed to determine their collective diagnostic significance. Results: Among 93 patients who were pathologically diagnosed with pancreatic neuroendocrine tumors and underwent [68Ga]-DOTATOC PET/CT, 48 with well-differentiated, non-functional pancreatic neuroendocrine tumors without accompanying genetic syndromes were included. The pancreatic neuroendocrine tumors were classified as WHO grade 1 (n = 30, 62.5%) and grade 2 (n = 18, 37.5%), with tumors in 25% of the patients exhibiting initial metastases. A higher incidence of metastasis was observed in larger metabolically active tumors (somatostatin receptor-expressing tumor volume, p < 0.001; total lesion somatostatin receptor expression, p < 0.001). Conclusions: Volumetric parameters derived from [68Ga]-DOTATOC PET/CT correlates with initial metastasis in well-differentiated pancreatic neuroendocrine tumors. Full article
(This article belongs to the Section Clinical Research of Cancer)
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10 pages, 1074 KiB  
Article
Prognostic Value of Very Early Interim FDG PET/CT After Single Cycle of Chemotherapy for 10-Year Survival in Diffuse Large B-Cell Lymphoma
by Eun Ji Han, Hye Lim Park, Seung-Ah Yahng, Gi-June Min, Byung-Ock Choi, Gyeongsin Park, Joo Hyun O and Seok-Goo Cho
Cancers 2025, 17(6), 926; https://doi.org/10.3390/cancers17060926 - 8 Mar 2025
Viewed by 1386
Abstract
Background/Objectives This study aimed to evaluate whether very early interim 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after a single cycle of first-line chemotherapy predicts long-term survival outcome in patients with diffuse large B-cell lymphoma (DLBCL). Methods A total of 51 [...] Read more.
Background/Objectives This study aimed to evaluate whether very early interim 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after a single cycle of first-line chemotherapy predicts long-term survival outcome in patients with diffuse large B-cell lymphoma (DLBCL). Methods A total of 51 patients (31 males and 20 females; mean age 55 years) had four FDG PET/CT studies, at baseline and after one, three, and six cycles of chemotherapy (PET0, PET1, PET3, and PET6). Visually and quantitatively assessed PET parameters were analyzed for associations with long-term survival. Results The estimated 10-year progression-free survival (PFS) and overall survival (OS) was 48% and 61%, respectively. During a median follow-up of 63 months (range 9–134), 17 patients (33%) exhibited disease progression and 15 (29%) died. On PET1, all but one showed decreased FDG uptake, and all showed decreased metabolic tumor volume. None of the PET1 or PET3 parameters were associated with survival. The PET6 parameters retained independent predictive value for OS after adjustment for the International Prognostic Index. Negative PET6 was associated with longer PFS (mean 99 vs. 50 mo, p = 0.04) and OS (mean 107 vs. 57 mo, p = 0.02). Con-clusions The FDG PET/CT parameters obtained after a single cycle of chemotherapy were not associated with long-term survival in DLBCL, while negative end-of-therapy FDG PET/CT was associated with longer PFS and OS. Tumor regression very early into first-line chemotherapy was not as clinically relevant as the presence of viable tumor on FDG PET/CT at the end of therapy for predicting long-term outcomes. Full article
(This article belongs to the Collection Imaging Biomarker in Oncology)
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23 pages, 9726 KiB  
Article
Comparing 68Ga-Pentixafor,18F-FDG PET/CT and Chemokine Receptor 4 Immunohistochemistry Staining in Breast Cancer: A Prospective Cross Sectional Study
by Bawinile Hadebe, Lerwine Harry, Lerato Gabela, Thembelihle Nxasana, Nontobeko Ndlovu, Venesen Pillay, Siphelele Masikane, Maryam Patel, Dineo Mpanya, Ines Buccimaza, Mpumelelo Msimang, Colleen Aldous, Mike Sathekge and Mariza Vorster
Cancers 2025, 17(5), 763; https://doi.org/10.3390/cancers17050763 - 24 Feb 2025
Cited by 1 | Viewed by 1002
Abstract
Background. CXCR4 is a chemokine receptor that is frequently overexpressed in invasive breast cancer and plays a major role in tumor proliferation, aggressiveness and metastasis. The aim of this prospective study was to establish the value of CXCR4-directed PET imaging in patients [...] Read more.
Background. CXCR4 is a chemokine receptor that is frequently overexpressed in invasive breast cancer and plays a major role in tumor proliferation, aggressiveness and metastasis. The aim of this prospective study was to establish the value of CXCR4-directed PET imaging in patients with breast cancer using the novel CXCR4-targeted PET probe 68Ga-Pentixafor by comparing it with 18F-FDG PET/CT (n = 40). Materials and methods. In this prospective cross-sectional study, fifty-one patients with breast cancer aged 36–81 (median (Q1-Q3) 51 (42.5–63)), n = 47 (92%) with initially diagnosed and n = 4 (8%) patients with recurrent breast cancer, underwent CXCR4-targeted PET imaging using 68Ga-Pentixafor. Maximum standardized uptake values (SUVmax), total lesion glycolysis (TLG) or total lesion uptake (TLU), metabolic tumor volume (MTV) and tumor-to-background ratios (TBR) of tumor lesions were measured and correlated with pathological prognostic factors, molecular subtypes and CXCR4 immunohistochemistry (IHC) staining. 18F-FDG PET/CT images were available in 40 of 51 cases (82%) and were compared semi-quantitatively. The patients were followed up for a median of 11 months (range 4–80 months) to determine whether CXCR4 expression correlated with survival. Results. 68Ga-Pentixafor-PET/CT was visually positive in 49/51 (96%) of the cases; in addition, [18F]FDG demonstrated a higher SUVmax compared to 68Ga-Pentixafor. The mean SUVmax was 7.26 ± 2.84 and 18.8 ± 9.1 for 68Ga-Pentixafor and [18F]FDG, respectively. Thirty-seven percent (18/51) of patients had triple-negative breast cancer and 25/51 (49%) had estrogen receptor (ER+) disease. There was a statistically significant correlation between tumor grade, proliferative index (Ki-67) and SUVmax obtained from 68Ga-Pentixafor PET p = 0.002. There was no correlation between the SUVmax obtained from 68Ga-Pentixafor and PET molecular subtypes, estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status; however, triple-negative breast cancers had more avid 68Ga-Pentixafor accumulation compared to luminals A and B. The median (Q1–Q3) 68Ga-Pentixafor TLU was significantly higher in HIV-positive (376 (219–881)) compared to HIV-negative (174 (105–557)) breast cancer patients. Conclusions. In conclusion, 68Ga-Pentixafor had a sensitivity of 96% and a specificity of 100% for detecting primary breast cancer; in addition, 68Ga-Pentixafor exhibited significantly higher uptake in patients with higher tumor grade, high proliferative index and triple-negative breast cancer (TNBC), as well as HIV-infected breast cancer patients, highlighting the potential clinical utility and prognostic role of CXCR4-targeted PET imaging in aggressive breast cancer. Notably, 68Ga-Pentixafor complements 18F-FDG by detecting more metastasis in the brain and the skull where FDG has limitations, while 18F-FDG remains superior for detecting skeletal metastasis. Future research should further explore the potential of CXCR4-targeted PET imaging in selecting patients with triple-negative breast cancer and high-grade breast cancer who may benefit from CXCR4-targeted therapies, particularly in the context of HIV co-infection. Full article
(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)
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13 pages, 2166 KiB  
Article
Prognostic Value of Pretreatment 18F-FDG-PET/CT Metabolic Parameters in Advanced High-Grade Serous Ovarian Cancer
by Daniela Travaglio Morales, Mónica Coronado Poggio, Carlos Huerga Cabrerizo, Itsaso Losantos García, Cristina Escabias del Pozo, Carmen Lancha Hernández, Sonia Rodado Marina and Luis Domínguez Gadea
Cancers 2025, 17(4), 698; https://doi.org/10.3390/cancers17040698 - 19 Feb 2025
Viewed by 802
Abstract
Aim: To assess the prognostic value of pretreatment 18F-FDG-PET/CT quantitative metabolic parameters in patients with advanced high-grade serous ovarian cancer (HGSOC). Methods: A review of 47 patients diagnosed with advanced HGSOC between 2012 and 2020 in our center was performed, evaluating pretreatment [...] Read more.
Aim: To assess the prognostic value of pretreatment 18F-FDG-PET/CT quantitative metabolic parameters in patients with advanced high-grade serous ovarian cancer (HGSOC). Methods: A review of 47 patients diagnosed with advanced HGSOC between 2012 and 2020 in our center was performed, evaluating pretreatment 18F-FDG-PET/CT metabolic parameters: maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and metabolic tumoral volume (MTV). Two experienced nuclear medicine physicians evaluated the images, thereby obtaining quantitative parameters semiautomatically classifying the volume of interest (VOI) as the target (t): VOI with the highest SUVmax normalized by lean body mass (SUVmax(lbm)), non target (nt) and total (sum of target and non-target VOIs). The disease-free survival (DFS) and overall survival (OS) were calculated. Optimal cutoff values with ROC curves/median values were used. The Correlation between metabolic parameters and DFS/OS was determined using univariate and survival-curves analysis. Results: The median DFS was 18 months (2.5–55) and the OS 33.6 months (2.5–92). The MTVtotal, MTV(t), TLGtotal and TLG(t) were significantly associated with DFS (p = 0.005, 0.01, 0.04 and 0.04, respectively). The patients with MTVtotal > 427.8 cm3 and MTVtarget > 434 cm3 had shorter DFS than the patients with lower values (18.8 versus 31 months and 15.6 versus 30, p = 0.02 and 0.01, respectively). The patients with higher TLGtotal and TLG(t) values tended to have worse DFS (p = 0.26 and 0.31, respectively). In a multivariate analysis, the MTVtotal was statistically significantly associated with DFS (p = 0.003). No correlation was found with OS. Conclusions: Pretreatment MTVtotal and MTV(t) appear to be predictive of relapse in patients with advanced HGSOC. Full article
(This article belongs to the Special Issue Recent Updates on Imaging and Staging of Gynecologic Cancers)
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24 pages, 3097 KiB  
Systematic Review
A Systematic Review of the Applications of Deep Learning for the Interpretation of Positron Emission Tomography Images of Patients with Lymphoma
by Theofilos Kanavos, Effrosyni Birbas and Theodoros P. Zanos
Cancers 2025, 17(1), 69; https://doi.org/10.3390/cancers17010069 - 29 Dec 2024
Cited by 1 | Viewed by 1871
Abstract
Background: Positron emission tomography (PET) is a valuable tool for the assessment of lymphoma, while artificial intelligence (AI) holds promise as a reliable resource for the analysis of medical images. In this context, we systematically reviewed the applications of deep learning (DL) [...] Read more.
Background: Positron emission tomography (PET) is a valuable tool for the assessment of lymphoma, while artificial intelligence (AI) holds promise as a reliable resource for the analysis of medical images. In this context, we systematically reviewed the applications of deep learning (DL) for the interpretation of lymphoma PET images. Methods: We searched PubMed until 11 September 2024 for studies developing DL models for the evaluation of PET images of patients with lymphoma. The risk of bias and applicability concerns were assessed using the prediction model risk of bias assessment tool (PROBAST). The articles included were categorized and presented based on the task performed by the proposed models. Our study was registered with the international prospective register of systematic reviews, PROSPERO, as CRD42024600026. Results: From 71 papers initially retrieved, 21 studies with a total of 9402 participants were ultimately included in our review. The proposed models achieved a promising performance in diverse medical tasks, namely, the detection and histological classification of lesions, the differential diagnosis of lymphoma from other conditions, the quantification of metabolic tumor volume, and the prediction of treatment response and survival with areas under the curve, F1-scores, and R2 values of up to 0.963, 87.49%, and 0.94, respectively. Discussion: The primary limitations of several studies were the small number of participants and the absence of external validation. In conclusion, the interpretation of lymphoma PET images can reliably be aided by DL models, which are not designed to replace physicians but to assist them in managing large volumes of scans through rapid and accurate calculations, alleviate their workload, and provide them with decision support tools for precise care and improved outcomes. Full article
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17 pages, 3465 KiB  
Article
The Impact of Bone Marrow Involvement on Prognosis in Diffuse Large B-Cell Lymphoma: An 18F-FDG PET/CT Volumetric Segmentation Study
by Andrej Doma, Andrej Studen and Barbara Jezeršek Novaković
Cancers 2024, 16(22), 3762; https://doi.org/10.3390/cancers16223762 - 7 Nov 2024
Cited by 2 | Viewed by 1579
Abstract
Background: This study assessed the prognostic value of tumor burden in bone marrow (BM) and total disease (TD), as depicted on 18F-FDG PET/CT in 140 DLBCL patients, for complete remission after first-line systemic treatment (iCR) and 3- and 5-year overall survival (OS3 and [...] Read more.
Background: This study assessed the prognostic value of tumor burden in bone marrow (BM) and total disease (TD), as depicted on 18F-FDG PET/CT in 140 DLBCL patients, for complete remission after first-line systemic treatment (iCR) and 3- and 5-year overall survival (OS3 and OS5). Methods: Baseline 18F-FDG PET/CT scans of 140 DLBCL patients were segmented to quantify metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax in BMI, findings elsewhere (XL), and TD. Results: Bone marrow involvement (BMI) presented in 35 (25%) patients. Median follow-up time was 47 months; 79 patients (56%) achieved iCR. iCR was significantly associated with TD MTV, XL MTV, BM PET positivity, and International Prognostic Index (IPI). OS3 was significantly worse with TD MTV, XL MTV, IPI, and age. OS5 was significantly associated with IPI, but not with MTVs and TLGs. Univariate factors predicting OS3 were XL MTV (hazard ratio [HR] = 1.29), BMI SUVmax (HR = 0.56), and IPI (HR = 1.92). By multivariate analysis, higher IPI (HR = 2.26) and BMI SUVmax (HR = 0.91) were significant independent predictors for OS3. BMI SUVmax resulted in a negative coefficient and hence indicated a protective effect. Conclusions: Baseline 18F-FDG PET/CT MTV is significantly associated with survival. BMI identified on 18F-FDG PET/CT allows appropriate treatment that may improve survival. Full article
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23 pages, 5248 KiB  
Article
Preclinical Multi-Omic Assessment of Pioglitazone in Skeletal Muscles of Mice Implanted with Human HER2/neu Overexpressing Breast Cancer Xenografts
by Stuart A. Clayton, Alan D. Mizener, Marcella A. Whetsell, Lauren E. Rentz, Ethan M. Meadows, Werner J. Geldenhuys and Emidio E. Pistilli
Cancers 2024, 16(21), 3640; https://doi.org/10.3390/cancers16213640 - 29 Oct 2024
Cited by 1 | Viewed by 1898
Abstract
Background/Objectives: Breast cancer (BC) is the second most commonly diagnosed cancer worldwide and is accompanied by fatigue during both active disease and remission in the majority of cases. Our lab has measured fatigue in isolated muscles from treatment-naive BC patient-derived orthotopic xenograft [...] Read more.
Background/Objectives: Breast cancer (BC) is the second most commonly diagnosed cancer worldwide and is accompanied by fatigue during both active disease and remission in the majority of cases. Our lab has measured fatigue in isolated muscles from treatment-naive BC patient-derived orthotopic xenograft (BC-PDOX) mice. Here, we conducted a preclinical trial of pioglitazone in BC-PDOX mice to determine its efficacy in ameliorating BC-induced muscle fatigue, as well as its effects on transcriptomic, metabolomic, and lipidomic profiles in skeletal muscle. Methods: The pioglitazone and vehicle groups were treated orally for 4 weeks upon reaching a tumor volume of 600 mm3. Whole-animal indirect calorimetry was used to evaluate systemic metabolic states. The transcriptome was profiled using short-read bulk RNA sequencing (RNA-seq). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to profile the metabolome and lipidome. Fast and slow skeletal muscle function were evaluated using isolated ex vivo testing. Results: Pioglitazone was associated with a 16.634% lower average O2 consumption (mL∙h−1, p = 0.035), 16.309% lower average CO2 production (mL∙h−1, p = 0.022), and 16.4% lower cumulative energy expenditure (EE) (kcal∙h−1, p = 0.035), with no changes in substrate utilization. RNA-seq supported the downstream effects of pioglitazone on target genes and displayed considerable upregulation of mitochondrial bioenergetic pathways. K-means cluster 5 showed enrichment of the PPAR signaling pathway (adj. p < 0.05, Log2FC = 2.58). Skeletal muscle metabolomic and lipidomic profiles exhibited dysregulation in response to BC, which was partially restored in pioglitazone-treated mice compared to vehicle-treated BC-PDOX mice. In particular, the overall abundance of total ceramide levels was significantly lower in the PioTx group (−46.327%, p = 0.048). Despite molecular support for pioglitazone’s efficacy, isolated muscle function was not affected by pioglitazone treatment. No significant difference in the area under the fatigue curve (AUC) was found between the pioglitazone and vehicle groups (p = 0.596). Conclusions: BC induces multi-omic dysregulation in skeletal muscle, which pioglitazone partially ameliorates. Future research should focus on profiling systemic metabolic dysfunction, identifying molecular biomarkers of fatigue, and testing alternative pioglitazone treatment regimens. Full article
(This article belongs to the Collection Oncology: State-of-the-Art Research in the USA)
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12 pages, 2042 KiB  
Article
Analysis of Molecular Imaging Biomarkers Derived from [18F]FDG PET/CT in mCRPC: Whole-Body Total Lesion Glycolysis (TLG) Predicts Overall Survival in Patients Undergoing [225Ac]Ac-PSMA-617-Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy
by Caroline Burgard, Fadi Khreish, Lukas Dahlmanns, Arne Blickle, Moritz B. Bastian, Tilman Speicher, Stephan Maus, Andrea Schaefer-Schuler, Mark Bartholomä, Sven Petto, Samer Ezziddin and Florian Rosar
Cancers 2024, 16(20), 3532; https://doi.org/10.3390/cancers16203532 - 19 Oct 2024
Viewed by 1671
Abstract
Background/Objectives: The augmentation of [177Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [225Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [18F]FDG PET/CT-derived molecular [...] Read more.
Background/Objectives: The augmentation of [177Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [225Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [18F]FDG PET/CT-derived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT in n = 33 patients with insufficient response on [177Lu]Lu-PSMA-617 monotherapy. Methods: Six different molecular imaging parameters at baseline, i.e., before initiation of PSMA tandem RLT with respect to SUVmax, SUVpeak, SUV5, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were tested for association with response and overall survival (OS). Results: After the initiation of augmentation, 24.2% of patients with a previously insufficient response experienced partial remission, and 39.4% experienced stable disease. The median OS was 7 months (95% CI: 4–11 months). None of the tested parameters were able to predict the response (all p > 0.529). In contrast, the [18F]FDG PET/CT-derived whole-body molecular imaging parameter TLG was significantly (p = 0.029) associated with OS of patients undergoing [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT after insufficient response to [177Lu]Lu-PSMA-617 monotherapy. Conclusion: Implementing [18F]FDG PET/CT in the management of PSMA-RLT in clinical practice may contribute to outcome prediction and provide a route to more individualized management in mCRPC. Full article
(This article belongs to the Collection Imaging Biomarker in Oncology)
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17 pages, 2260 KiB  
Article
From Phantoms to Patients: Improved Fusion and Voxel-Wise Analysis of Diffusion-Weighted Imaging and FDG-Positron Emission Tomography in Positron Emission Tomography/Magnetic Resonance Imaging for Combined Metabolic–Diffusivity Index (cDMI)
by Katharina Deininger, Patrick Korf, Leonard Lauber, Robert Grimm, Ralph Strecker, Jochen Steinacker, Catharina S. Lisson, Bernd M. Mühling, Gerlinde Schmidtke-Schrezenmeier, Volker Rasche, Tobias Speidel, Gerhard Glatting, Meinrad Beer, Ambros J. Beer and Wolfgang Thaiss
Diagnostics 2024, 14(16), 1787; https://doi.org/10.3390/diagnostics14161787 - 16 Aug 2024
Viewed by 1490
Abstract
Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially [...] Read more.
Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially in diffusion-weighted imaging (DWI), which would be, however, crucial to derive biologically meaningful information. Thus, our aim was to optimize fusion and voxel-wise analyses of DWI and standardized uptake values (SUVs) using a novel software for m2p analyses. Using research software, we evaluated the precision of image co-registration and voxel-wise analyses including the rigid and elastic 3D registration of DWI and [18F]-Fluorodeoxyglucose (FDG)-PET from an integrated PET/MR system. We analyzed DWI distortions with a volume-preserving constraint in three different 3D-printed phantom models. A total of 12 PET/MR-DWI clinical datasets (bronchial carcinoma patients) were referenced to the T1 weighted-DIXON sequence. Back mapping of scatterplots and voxel-wise registration was performed and compared to the non-optimized datasets. Fusion was rated using a 5-point Likert scale. Using the 3D-elastic co-registration algorithm, geometric shapes were restored in phantom measurements; the measured ADC values did not change significantly (F = 1.12, p = 0.34). Reader assessment showed a significant improvement in fusion precision for DWI and morphological landmarks in the 3D-registered datasets (4.3 ± 0.2 vs. 4.6 ± 0.2, p = 0.009). Most pronounced differences were noted for the chest wall (p = 0.006), tumor (p = 0.007), and skin contour (p = 0.014). Co-registration increased the number of plausible ADC and SUV combinations by 25%. The volume-preserving elastic 3D registration of DWI significantly improved the precision of fusion with anatomical sequences in phantom and clinical datasets. The research software allowed for a voxel-wise analysis and visualization of [18F]FDG-PET/MR data as a “combined diffusivity–metabolic index” (cDMI). The clinical value of the optimized PET/MR biomarker can thus be tested in future PET/MR studies. Full article
(This article belongs to the Special Issue New Trends and Advances of MRI and PET Hybrid Imaging in Diagnostics)
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9 pages, 1560 KiB  
Article
Deciphering Tumor Response: The Role of Fluoro-18-d-Glucose Uptake in Evaluating Targeted Therapies with Tyrosine Kinase Inhibitors
by Kalevi Kairemo, Mohamed Gouda, Hubert H. Chuang, Homer A. Macapinlac and Vivek Subbiah
J. Clin. Med. 2024, 13(11), 3269; https://doi.org/10.3390/jcm13113269 - 31 May 2024
Cited by 1 | Viewed by 1192
Abstract
Background/Objectives: 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 [ [...] Read more.
Background/Objectives: 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 [18F]FDG-PET monitoring of tumor response in patients. Methods: 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 [18F]FDG-PET/CT imaging. Notably, our patients harbored alterations in BRAFV600, RET, and c-KIT and exhibited positive responses to the targeted treatment. Results: Our analysis revealed that FDG data derived from SUVmax, TLG, and MTV offered quantifiable outcomes that were consistent with the measurements of tumor size. Conclusions: These findings lend support to the notion that the inhibition of GLUT-1, as a consequence of treatment efficacy, could be indirectly gauged through [18F] FDG-PET/CT imaging in cancer patients undergoing TKI therapy. Full article
(This article belongs to the Special Issue PET Imaging in the Evaluation of Cancer Treatment)
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14 pages, 3239 KiB  
Systematic Review
The Diagnostic Performance of 2-[18F]FDG PET/CT in Identifying Richter Transformation in Chronic Lymphocytic Leukemia: An Updated Systematic Review and Bivariate Meta-Analysis
by Domenico Albano, Alessio Rizzo, Manuela Racca, Barbara Muoio, Francesco Bertagna and Giorgio Treglia
Cancers 2024, 16(9), 1778; https://doi.org/10.3390/cancers16091778 - 5 May 2024
Cited by 5 | Viewed by 1966
Abstract
Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission [...] Read more.
Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5–93.3), a pooled specificity of 48.1% (95% CI: 27–69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence. Full article
(This article belongs to the Special Issue Clinical Research Advances in Chronic Lymphocytic Leukemia (CLL))
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13 pages, 3265 KiB  
Review
Pre-Treatment and Post-Treatment I-131 Imaging in Differentiated Thyroid Carcinoma
by Jasna Mihailović
J. Clin. Med. 2024, 13(7), 1984; https://doi.org/10.3390/jcm13071984 - 29 Mar 2024
Cited by 4 | Viewed by 5126
Abstract
Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, [...] Read more.
Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, is controversial. Dx WBI has been abandoned in most nuclear medicine centers long ago. Planar low-dose dxWBI provides the volume of postoperative thyroid remnants, but it cannot detect occult metastatic foci in the neck. The modern integrated multimodality, i.e., SPECT/CT imaging, provides three dimensional images and accurate anatomic/metabolic data. This hybrid technology offers better spatial resolution but not better sensitivity. Dx WBI has low theranostic power because of the radioiodine indifference and low detection sensitivity for small-volume nodal disease in the neck. Since dx WBI cannot clarify the paratracheal cervical uptake, thyroid remnants may be easily misinterpreted as nodal disease, leading to a false N upstaging (from N0 stage to N1 stage) in DTC patients. Post-ablation I-131 imaging has a significant role in the initial staging of radioiodine-avid DTC and in the identification of non-radioiodine avid tumors. Additionally, SPECT/CT in the post-treatment setting provides more accurate initial TNM staging and better risk stratification of DTC patients. Post-treatment I-131 imaging is obligatory and must be performed in all DTC patients who receive radioiodine treatment. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
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