ABSTRACT
68Ga-DOTA NOC PET-CT imaging has been shown to have high accuracy for the evaluation of neuroendocrine tumours. We present the case of a 59-year-old male with well differentiated gastric neuroendocrine tumour (grade II) treated with surgery. 68Ga-DOTA NOC PET/CT was performed to rule out metastasis. 68Ga-DOTA NOC showed physiological uptake in the bilateral adrenal and horseshoe kidney appearing as the famous character Super Mario. There is no evidence of any abnormal somatostatin avid lesion.
Subject(s)
Neuroendocrine Tumors , Positron Emission Tomography Computed Tomography , Receptors, Somatostatin , Stomach Neoplasms , Humans , Male , Middle Aged , Positron Emission Tomography Computed Tomography/methods , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Receptors, Somatostatin/metabolism , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Radiopharmaceuticals , Organometallic Compounds , Adrenal Glands/diagnostic imaging , Adrenal Glands/pathologyABSTRACT
Purpose: This study aims to elucidate the role of quantitative SSTR-PET metrics and clinicopathological biomarkers in the progression-free survival (PFS) and overall survival (OS) of neuroendocrine tumors (NETs) treated with peptide receptor radionuclide therapy (PRRT). Methods: A retrospective analysis including 91 NET patients (M47/F44; age 66 years, range 34-90 years) who completed four cycles of standard 177Lu-DOTATATE was conducted. SSTR-avid tumors were segmented from pretherapy SSTR-PET images using a semiautomatic workflow with the tumors labeled based on the anatomical regions. Multiple image-based features including total and organ-specific tumor volume and SSTR density along with clinicopathological biomarkers including Ki-67, chromogranin A (CgA) and alkaline phosphatase (ALP) were analyzed with respect to the PRRT response. Results: The median OS was 39.4 months (95% CI: 33.1-NA months), while the median PFS was 23.9 months (95% CI: 19.3-32.4 months). Total SSTR-avid tumor volume (HR = 3.6; P = 0.07) and bone tumor volume (HR = 1.5; P = 0.003) were associated with shorter OS. Also, total tumor volume (HR = 4.3; P = 0.01), liver tumor volume (HR = 1.8; P = 0.05) and bone tumor volume (HR = 1.4; P = 0.01) were associated with shorter PFS. Furthermore, the presence of large lesion volume with low SSTR uptake was correlated with worse OS (HR = 1.4; P = 0.03) and PFS (HR = 1.5; P = 0.003). Among the biomarkers, elevated baseline CgA and ALP showed a negative association with both OS (CgA: HR = 4.9; P = 0.003, ALP: HR = 52.6; P = 0.004) and PFS (CgA: HR = 4.2; P = 0.002, ALP: HR = 9.4; P = 0.06). Similarly, number of prior systemic treatments was associated with shorter OS (HR = 1.4; P = 0.003) and PFS (HR = 1.2; P = 0.05). Additionally, tumors originating from the midgut primary site demonstrated longer PFS, compared to the pancreas (HR = 1.6; P = 0.16), and those categorized as unknown primary (HR = 3.0; P = 0.002). Conclusion: Image-based features such as SSTR-avid tumor volume, bone tumor involvement, and the presence of large tumors with low SSTR expression demonstrated significant predictive value for PFS, suggesting potential clinical utility in NETs management. Moreover, elevated CgA and ALP, along with an increased number of prior systemic treatments, emerged as significant factors associated with worse PRRT outcomes.
Subject(s)
Biomarkers, Tumor , Neuroendocrine Tumors , Octreotide , Organometallic Compounds , Humans , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/metabolism , Aged , Middle Aged , Organometallic Compounds/therapeutic use , Male , Female , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Adult , Retrospective Studies , Aged, 80 and over , Biomarkers, Tumor/metabolism , Positron-Emission Tomography/methods , Receptors, Somatostatin/metabolism , Radiopharmaceuticals , Treatment Outcome , Chromogranin A/metabolism , Alkaline Phosphatase/metabolism , Ki-67 Antigen/metabolism , Progression-Free Survival , Tumor BurdenABSTRACT
Background: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.
Subject(s)
Indoles , Isoindoles , Multimodal Imaging , Nanoparticles , Photochemotherapy , Photosensitizing Agents , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Multimodal Imaging/methods , Animals , Humans , Indoles/chemistry , Indoles/pharmacology , Photochemotherapy/methods , Nanoparticles/chemistry , Mice , Zinc Compounds/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Cell Line, Tumor , Photoacoustic Techniques/methods , Photothermal Therapy/methods , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/drug therapy , Mice, Inbred BALB C , Phototherapy/methods , FemaleABSTRACT
Metal-organic frameworks (MOFs) are materials with potential applications in fields such as gas adsorption and separation, catalysis, and biomedicine. Attempts to enhance the utility of MOFs have involved the preparation of various composites, including polymer-grafted MOFs. By directly grafting polymers to the external surface of MOFs, issues of incompatibility between polymers and MOFs can be overcome. Polymer brushes grafted from the surface of MOFs can serve to stabilize the MOF while enabling particle assembly into self-assembled metal-organic framework monolayers (SAMMs) via polymer-polymer interactions. Control over the chemical composition and molecular weight of the grafted polymer can allow for tuning of the SAMM characteristics. In this work, instructions are provided on how to immobilize a chain transfer agent (CTA) onto the surface of the MOF UiO-66 (UiO = Universitetet i Oslo). The CTA serves as initiation sites for the growth of polymers. Once polymer chains are grown from the MOF surface, the formation of SAMMs is achieved through self-assembly at an air-water interface. The resulting SAMMs are characterized and shown to be freestanding by scanning electron microscopy imaging. The methods presented in this paper are expected to make the preparation of SAMMs more accessible to the research community and thereby expand their potential use as a MOF-polymer composite.
Subject(s)
Polymers , Polymers/chemistry , Organometallic Compounds/chemistry , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/chemical synthesis , Phthalic AcidsABSTRACT
A patient with a neuroendocrine tumor and history of coronary artery disease underwent PET with 68Ga-DOTATATE PET tracer for tumor visualization. Analysis of the scan showed uptake of 68Ga-DOTATATE in the left ventricle corresponding to previous myocardial infarct. 68Ga-DOTATATE binds by somatostatin receptors (SSTR) and it has been proposed that it may be useful for the detection of cardiac inflammatory lesions. We aimed to test whether SSTR could be upregulated in cardiac fibrotic scar. We analyzed SSTR in cardiac samples from patients with end-stage ischemic cardiomyopathy (ICM, n = 8) and control hearts (n = 5). In mature ICM tissue, SSTR1 and SSTR2 expression was unchanged and SSTR5 expression was significantly decreased in ICM samples vs. control. Immunohistochemistry showed increased SSTR1 and SSTR2 in ICM. Areas with SSTR1 or SSTR2 staining were often adjacent to fibrotic areas. The majority of SSTR1 and SSTR2 staining localized in cardiomyocytes in fibrotic scar-rich areas where CD68 macrophage staining was not present. SSTR are occasionally upregulated in cardiac fibrotic areas. When using 68Ga-DOTATATE PET tracer to detect cardiac sarcoidosis or atherosclerotic plaque, the possibility of tracer uptake in fibrotic areas should be considered.
Subject(s)
Fibrosis , Myocardium , Organometallic Compounds , Receptors, Somatostatin , Humans , Receptors, Somatostatin/metabolism , Fibrosis/metabolism , Myocardium/metabolism , Myocardium/pathology , Male , Middle Aged , Female , Aged , Positron-Emission TomographyABSTRACT
177Lu-DOTATATE therapy is an effective treatment for advanced neuroendocrine tumors, despite its dose-limiting hematotoxicity. Herein, the significance of off-target splenic irradiation is unknown. Our study aims to identify predictive markers of peptide receptor radionuclide therapy-induced leukopenia. Methods: We retrospectively analyzed blood counts and imaging data of 88 patients with histologically confirmed, unresectable metastatic neuroendocrine tumors who received 177Lu-DOTATATE treatment at our institution from February 2009 to July 2021. Inclusion criterium was a tumor uptake equivalent to or greater than that in the liver on baseline receptor imaging. We excluded patients with less than 24 mo of follow-up and those patients who received fewer than 4 treatment cycles, additional therapies, or blood transfusions during follow-up. Results: Our study revealed absolute and relative white blood cell counts and relative spleen volume reduction as independent predictors of radiation-induced leukopenia at 24 mo. However, a 30% decline in spleen volume 12 mo after treatment most accurately predicted patients proceeding to leukopenia at 24 mo (receiver operating characteristic area under the curve of 0.91, sensitivity of 0.93, and specificity of 0.90), outperforming all other parameters by far. Conclusion: Automated splenic volume assessments demonstrated superior predictive capabilities for the development of leukopenia in patients undergoing 177Lu-DOTATATE treatment compared with conventional laboratory parameters. The reduction in spleen size proves to be a valuable, routinely available, and quantitative imaging-based biomarker for predicting radiation-induced leukopenia. This suggests potential clinical applications for risk assessment and management.
Subject(s)
Leukopenia , Neuroendocrine Tumors , Octreotide , Organometallic Compounds , Receptors, Peptide , Spleen , Humans , Female , Leukopenia/etiology , Male , Spleen/diagnostic imaging , Spleen/radiation effects , Middle Aged , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Octreotide/adverse effects , Retrospective Studies , Aged , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/diagnostic imaging , Receptors, Peptide/metabolism , Organometallic Compounds/adverse effects , Organometallic Compounds/therapeutic use , Organ Size , Adult , Biomarkers , Aged, 80 and overABSTRACT
Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.
Subject(s)
Antineoplastic Agents , Indoles , Isoindoles , Photochemotherapy , Photosensitizing Agents , Humans , Indoles/chemistry , Indoles/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Iridium/chemistry , Iridium/pharmacology , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Zinc Compounds/chemistry , Reactive Oxygen Species/metabolism , Nanocapsules/chemistry , Cell Line, Tumor , Cell Survival/drug effectsABSTRACT
PURPOSE: To evaluate the performance of hepatobiliary MRI parameters as predictors of clinical response to chemotherapy in patients with initially unresectable colorectal cancer liver metastases (CRLM). METHODS: Eighty-five patients with initially unresectable CRLM were retrospectively enrolled from two hospitals and scanned using gadobenate dimeglumine-enhanced MRI before treatment. Therapy response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Conventional parameters (i.e., signal intensity [SI]) and radiomics features of portal venous phase (PVP) and hepatobiliary phase (HBP) images were analyzed between the responders and non-responders. Next, the combined model was constructed, and the area under the receiver operating characteristic (ROC) curve (AUC) was calculated. The relationship between the combined model and progression-free survival (PFS) was analyzed using Cox regression. RESULTS: Of the 85 patients from two hospitals, 42 were in the response group, and 43 were in the non-response group. Upon conducting five-fold cross-validation, the normalized relative enhancement (NRE) of CRLM during the PVP yielded an AUC of 0.625. Additionally, a radiomics feature derived from the tumor area in the HBP achieved an AUC of 0.698, while a separate feature extracted from the peritumoral region in the HBP recorded an AUC of 0.709. The model that integrated these three features outperformed the individual features, achieving an AUC of 0.818. Furthermore, the combined model exhibited a significant correlation with PFS (P < 0.001). CONCLUSION: The combined model, based on baseline hepatobiliary MRI, aids in predicting chemotherapeutic response and PFS in patients with initially unresectable CRLM.
Subject(s)
Colorectal Neoplasms , Contrast Media , Liver Neoplasms , Magnetic Resonance Imaging , Organometallic Compounds , Humans , Female , Male , Colorectal Neoplasms/pathology , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/drug therapy , Liver Neoplasms/secondary , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Magnetic Resonance Imaging/methods , Middle Aged , Retrospective Studies , Prognosis , Aged , Meglumine/analogs & derivatives , Adult , Predictive Value of Tests , Response Evaluation Criteria in Solid Tumors , Treatment Outcome , Aged, 80 and overABSTRACT
ABSTRACT: A 76-year-old woman with liver and bone metastasis of a duodenal neuroendocrine tumor received peptide receptor radionuclide therapy with 177 Lu-DOTATATE. Scintigraphy with SPECT/CT performed 4 days after the treatment demonstrated 177 Lu-DOTATATE uptake as multifocal ground glass opacities in the bilateral lungs. This uptake was considered to be due to COVID-19 pneumonia because the patient was infected with the virus 7 days prior to the treatment. The lung opacities became smaller, showing a decreased uptake, 2 months later, after the second treatment. 177 Lu-DOTATATE may be taken up during the active phase of COVID-19 pneumonia.
Subject(s)
COVID-19 , Lung , Octreotide , Organometallic Compounds , Pneumonia, Viral , Humans , COVID-19/diagnostic imaging , COVID-19/complications , Aged , Female , Lung/diagnostic imaging , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/complications , Pandemics , Single Photon Emission Computed Tomography Computed Tomography , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/complications , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/radiotherapyABSTRACT
Gas sensors based on ambipolar materials offer significant advantages in reducing the size of the analytical system and enhancing its efficiency. Here, bilayer heterojunction devices are constructed using different octafluorinated phthalocyanine complexes, with Zn and Co as metal centers, combined with a lutetium bisphthalocyanine complex (LuPc2). Stable p-type behavior is observed for the ZnF8Pc/LuPc2 device under both electron-donating (NH3) and -oxidizing (NO2 and O3) gaseous species, while the CoF8Pc/LuPc2 device exhibits n-type behavior under reducing gases and p-type behavior under oxidizing gases. The nature of majority of the charge carriers of Co-based devices varies depending on the nature of target gases, displaying an ambipolar behavior. Both heterojunction devices demonstrate stable and observable response toward all three toxic gases in the sub-ppm range. Remarkably, the Co-based device is highly sensitive toward ammonia with a limit of detection (LOD) of 200 ppb, whereas the Zn-based device demonstrates exceptional sensitivity toward oxidizing gases, with excellent LOD values of 4.9 and 0.75 ppb toward NO2 and O3, respectively, which makes it one of the most effective organic heterojunction sensors reported so far for oxidizing gases.
Subject(s)
Gases , Indoles , Zinc , Indoles/chemistry , Gases/analysis , Gases/chemistry , Zinc/chemistry , Zinc/analysis , Isoindoles , Limit of Detection , Cobalt/chemistry , Lutetium/chemistry , Ammonia/analysis , Nitrogen Dioxide/analysis , Nitrogen Dioxide/chemistry , Organometallic Compounds/chemistry , Air Pollutants/analysisABSTRACT
Neuroinflammation is one of the main mechanisms involved in the progression of neurodegenerative diseases (NDs), and microglial activation is the main feature of neuroinflammation. Polaprezinc (Pol), a chelator of L-carnosine and zinc, is widely used as a clinical drug for gastric ulcers. However, its potential effects on NDs remain unexplored. In LPS-induced BV-2 microglia, we found that Pol reduced the generation of NO and ROS and revealed inhibited expression of iNOS, COX-2, and inflammatory factors such as IL-6, TNF-α, and 1L-1ß by Pol using qRT-PCR and Western blotting. These effects were found to be associated with the suppression of the NF-κB signaling pathway. Moreover, we evaluated the potential synergistic effects of aspergillusidone G (Asp G) when combined with Pol. Remarkably, co-treatment with low doses of Asp G enhanced the NO inhibition by Pol from approximately 30% to 80% in LPS-induced BV2 microglia, indicating a synergistic anti-inflammatory effect. A bioinformatics analysis suggested that the synergistic mechanism of Asp G and Pol might be attributed to several targets, including NFκB1, NRF2, ABL1, TLR4, and PPARα. These findings highlight the anti-neuroinflammatory properties of Pol and its enhanced efficacy when combined with Asp G, proposing a novel therapeutic strategy for managing neuroinflammation in NDs.
Subject(s)
Anti-Inflammatory Agents , Carnosine , Lipopolysaccharides , Microglia , NF-kappa B , Organometallic Compounds , Microglia/drug effects , Microglia/metabolism , Animals , Mice , Lipopolysaccharides/pharmacology , Carnosine/pharmacology , Carnosine/analogs & derivatives , Anti-Inflammatory Agents/pharmacology , NF-kappa B/metabolism , Organometallic Compounds/pharmacology , Zinc Compounds/pharmacology , Computational Biology , Cell Line , Signal Transduction/drug effects , Neuroinflammatory Diseases/drug therapy , Drug Synergism , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolism , Nitric Oxide Synthase Type II/metabolismABSTRACT
Myocardial somatostatin PET uptake is observed not only in most patients with acute myocarditis (AM) but also in some oncology patients referred for routine somatostatin PET. This raises concerns about the specificity of somatostatin PET for detecting myocarditis. The current study aims to identify factors associated with the detection of myocardial uptake on somatostatin PET scans recorded for oncology indications and differential PET criteria that characterize myocardial uptake in AM patients. Methods: We analyzed factors associated with the detection of myocardial [68Ga]Ga-DOTATOC uptake in 508 [68Ga]Ga-DOTATOC PET scans from 178 patients, performed for confirmed or suspected oncologic disease (Onc-PET) and PET criteria that could differentiate myocardial [68Ga]Ga-DOTATOC uptake in 31 patients with MRI-ascertained AM (AM-PET) from that in the Onc-PET group. Results: Significant myocardial uptake was detected in 137 (26.9%) Onc-PET scans and was independently associated with somatostatin analog treatment (exp(ß), 0.805; 95% CI, 0.728-0.890; P < 0.001) and age (exp(ß), 1.005; 95% CI, 1.001-1.009; P = 0.012). A comparable model was selected for predicting the myocardial-to-blood SUVmax ratio using somatostatin analog treatment (P < 0.001) and history of coronary artery disease (P = 0.022). Myocardial uptake was detected in 12.9% (25/193) of Onc-PET scans from patients treated with somatostatin analogs but in 43.4% (59/136) of untreated patients over the median age of 64 y. Myocardial uptake was apparent in all 31 AM-PET scans, with volume and intensity of uptake dramatically higher than in the 137 Onc-PET scans showing myocardial uptake. A myocardial-to-blood SUVmax ratio threshold of 2.20 provided a sensitivity of 87% (27/31) and a specificity of 88% (44/50) for differentiating myocardial uptake between the AM-PET group and an Onc-PET group restricted to patients with clinical characteristics comparable to those of patients in the AM-PET group (≤64 y of age, no coronary artery disease history, and no somatostatin agonists). A myocardial uptake volume threshold of 18 cm3 provided comparable diagnostic accuracy (sensitivity, 84% [26/31]; specificity, 94% [47/50]). Conclusion: Myocardial uptake was detected in 26.9% of somatostatin PET scans recorded for oncology indications. This rate was decreased by somatostatin analog treatments and increased in older individuals. However, somatostatin PET scans, analyzed with the quantitative criterion of uptake intensity or volume, are able to identify AM and to differentiate it from myocardial uptake of other origins.
Subject(s)
Myocarditis , Myocardium , Octreotide , Somatostatin , Adult , Aged , Female , Humans , Male , Middle Aged , Acute Disease , Biological Transport , Diagnosis, Differential , Heart/diagnostic imaging , Myocarditis/diagnostic imaging , Myocarditis/metabolism , Myocardium/metabolism , Neoplasms/diagnostic imaging , Neoplasms/metabolism , Octreotide/analogs & derivatives , Octreotide/metabolism , Octreotide/pharmacokinetics , Organometallic Compounds/pharmacokinetics , Organometallic Compounds/metabolism , Positron-Emission Tomography , Radiopharmaceuticals/pharmacokinetics , Retrospective Studies , Somatostatin/analogs & derivatives , Somatostatin/metabolismABSTRACT
OBJECTIVE: We investigated metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on pre-treatment FDG-PET as prognostic markers for survival in patients with metastatic neuroendocrine neoplasms (NENs) receiving peptide receptor radionuclide therapy (PRRT). METHODS: A retrospective review of patients with metastatic NENs receiving PRRT was undertaken. Pre-treatment FDG-PET images were analyzed and variables collected included MTV and TLG (dichotomized by median into high vs low). Main Outcomes were overall survival (OS) and progression-free survival (PFS) by MTV and TLG (high vs low). RESULTS: One hundred five patients were included. Median age was 64 years (50% male). Main primary NEN sites were small bowel (43.8%) and pancreas (40.0%). Median MTV was 3.8 mL and median TLG was 19.9. Dichotomization formed identical cohorts regardless of whether MTV or TLG were used. Median OS was 72 months; OS did not differ based on MTV/TLG high versus low (47.4 months vs not reached; hazard ratio, 0.43; 95% confidence interval [CI], 0.18-1.04; P = 0.0594). Median PFS was 30.4 months; PFS differed based on MTV/TLG high versus low (21.6 months vs 45.7 months; hazard ratio, 0.35; 95% CI, 0.19-0.64; P = 0.007). CONCLUSIONS: Low MTV/TLG on pre-treatment FDG-PET was associated with longer PFS in metastatic NEN patients receiving PRRT.
Subject(s)
Fluorodeoxyglucose F18 , Neuroendocrine Tumors , Octreotide , Organometallic Compounds , Positron-Emission Tomography , Radiopharmaceuticals , Tumor Burden , Humans , Male , Middle Aged , Female , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/mortality , Retrospective Studies , Aged , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Positron-Emission Tomography/methods , Prognosis , Organometallic Compounds/therapeutic use , Adult , Receptors, Peptide/metabolism , Glycolysis , Aged, 80 and over , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/mortality , Progression-Free Survival , Treatment OutcomeABSTRACT
BACKGROUND: Exposure of humans and animals to heavy metals is increasing day-by-day; thus, lead even today remains of significant public health concern. According to CDC, blood lead reference value (BLRV) ranges from 3.5 µg/dl to 5 µg/dl in adults. Recently, almost 2.6% decline in male fertility per year has been reported but the cause is not well established. Lead (Pb2+) affects the size of testis, semen quality, and secretory functions of prostate. But the molecular mechanism(s) of lead toxicity in sperm cells is not clear. Thus, present study was undertaken to evaluate the adverse effects of lead acetate at environmentally relevant exposure levels (0.5, 5, 10 and 20 ppm) on functional and molecular dynamics of spermatozoa of bucks following in vitro exposure for 15 min and 3 h. RESULTS: Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb2+ modulated intracellular cAMP and Ca2+ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb2+ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria. CONCLUSIONS: Pb2+ not only mimics Ca2+ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca2+ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca2+ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.
Subject(s)
Acrosome Reaction , Acrosome , Calcium , Lead , Sperm Motility , Spermatozoa , Male , Spermatozoa/drug effects , Calcium/metabolism , Sperm Motility/drug effects , Animals , Acrosome/drug effects , Lead/toxicity , Acrosome Reaction/drug effects , Cyclic AMP/metabolism , Cattle , Membrane Potential, Mitochondrial/drug effects , Signal Transduction/drug effects , Semen Analysis , DNA Damage/drug effects , Organometallic Compounds/toxicity , Organometallic Compounds/pharmacologyABSTRACT
Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120 mg MgO, 120 mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.
Subject(s)
Dietary Supplements , Hyperoxaluria , Kidney Calculi , Magnesium Oxide , Humans , Magnesium Oxide/therapeutic use , Magnesium Oxide/administration & dosage , Female , Male , Kidney Calculi/urine , Kidney Calculi/prevention & control , Kidney Calculi/drug therapy , Kidney Calculi/metabolism , Adult , Hyperoxaluria/urine , Hyperoxaluria/drug therapy , Hyperoxaluria/complications , Double-Blind Method , Risk Factors , Middle Aged , Citric Acid/urine , Magnesium Compounds/therapeutic use , Magnesium Compounds/urine , Magnesium Compounds/pharmacology , Magnesium Compounds/administration & dosage , Organometallic CompoundsABSTRACT
Background Somatostatin receptors, and specifically somatostatin receptor type 2 (SSTR2), have primarily been associated with neuroendocrine tumors and have revolutionized the imaging and therapy of patients with these tumors. SSTR2 is expressed on other tumors at lower prevalence. Purpose To evaluate the potential of SSTR2-targeted imaging and therapy in patients with breast cancer. Materials and Methods In a preclinical experiment, SSTR2 expression was assessed in tissue microarrays of breast cancer samples using H-score analysis. H-scores higher than 50 (0-300 scale) were considered positive. Then, a prospective phase 2 clinical trial of SSTR2-targeted tetraazacyclododecane tetraacetic acid octreotate (Dotatate) PET/CT was performed in participants with biopsy-proven estrogen receptor (ER)-positive breast cancer from January to August 2023. A positive Dotatate PET/CT scan was defined as tumors with a Krenning score of 3 (avidity greater than liver) or 4 (avidity greater than spleen). The proportion of positive scans and the 95% CI were calculated. One participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET/CT result underwent treatment with SSTR2-targeted actinium 225 (225Ac) Dotatate. Results Preclinical microarrays demonstrated that 63 of 123 ER-positive breast cancer tissue samples (51% [95% CI: 42, 60]) but only 22 of 121 ER-negative breast cancer tissue samples (18% [95% CI: 12, 26]) were enriched for SSTR2 (P < .001). Thirty female participants (mean age, 66 years ± 15) with metastatic ER-positive breast cancer were accrued to the phase 2 SSTR2-targeted imaging trial and underwent Dotatate PET/CT. Dotatate PET/CT demonstrated that nine of 30 participants (30% [95% CI: 15, 49]) had tumors with Krenning scores of 3 or 4, indicating strong SSTR2 expression. SSTR2-targeted therapy with alpha-emitting 225Ac-Dotatate resulted in a near complete response in a heavily pretreated participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET result. Conclusion Molecular imaging targeting SSTR2 and radioligand therapy with SSTR2-targeted 225Ac-Dotatate enables a new therapeutic option for patients with metastatic breast cancer. Clinical trial registration no. NCT05880394 © RSNA, 2024 See also the editorial by Lin and Choyke in this issue.
Subject(s)
Breast Neoplasms , Organometallic Compounds , Positron Emission Tomography Computed Tomography , Receptors, Somatostatin , Humans , Female , Receptors, Somatostatin/metabolism , Positron Emission Tomography Computed Tomography/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Middle Aged , Organometallic Compounds/therapeutic use , Prospective Studies , Aged , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Radiopharmaceuticals , AdultABSTRACT
PURPOSE: This study aimed to investigate the efficiency of antimicrobial photodynamic therapy (aPDT) on Streptococcus mutans biofilm in the oral cavity using the photosensitizer chloroaluminum phthalocyanine encapsulated in chitosan nanoparticles (ClAlPc/Ch) at three preirradiation times. METHODS: Biofilms of Streptococcus mutans strains (ATCC 25,175) were cultivated on bovine tooth blocks and exposed to a 10% sucrose solution three times a day for 1 min over three consecutive days. The samples were randomly distributed into five treatment groups (n = 5): (I) aPDT with ClAlPc/Ch with a preirradiation time of 5 min (F5), (II) aPDT with ClAlPc/Ch with a preirradiation time of 15 min (F15), (III) aPDT with ClAlPc/Ch with a preirradiation time of 30 min (F30), (IV) 0.12% chlorhexidine digluconate (CHX), and (V) 0.9% saline solution (NaCl). After treatment, the S. mutans biofilms formed on each specimen were collected to determine the number of viable bacteria (colony-forming units (CFU)/mL). Data were analyzed for normality using the Shapiro-Wilk test and the analysis of variance (ANOVA) and Tukey HSD tests to analyze the number of viable bacteria (α = 0.05). RESULTS: The one-way ANOVA showed a difference between the groups (p = 0.0003), and the Tukey HSD posttest showed that CHX had the highest microbial reduction of S. mutans, not statistically different from the F5 and F15 groups, whereas the NaCl group had the lowest microbial reduction statistically similar to the F30 group. CONCLUSION: The results demonstrate that aPDT mediated by ClAlPc/Ch when used at preirradiation times of 5-15 min can be an effective approach in controlling cariogenic biofilm of S. mutans, being an alternative to 0.12% CHX.
Subject(s)
Biofilms , Chitosan , Nanoparticles , Photochemotherapy , Photosensitizing Agents , Streptococcus mutans , Streptococcus mutans/drug effects , Streptococcus mutans/radiation effects , Streptococcus mutans/physiology , Photochemotherapy/methods , Chitosan/pharmacology , Chitosan/chemistry , Nanoparticles/chemistry , Biofilms/drug effects , Biofilms/radiation effects , Animals , Cattle , Photosensitizing Agents/pharmacology , In Vitro Techniques , Indoles/pharmacology , Mouth/microbiology , Chlorhexidine/pharmacology , Chlorhexidine/analogs & derivatives , Microbial Viability/drug effects , Microbial Viability/radiation effects , Organometallic CompoundsABSTRACT
Not required for Clinical Vignette.
Subject(s)
Organometallic Compounds , Humans , Male , Organometallic Compounds/therapeutic use , Middle Aged , Gallium RadioisotopesABSTRACT
We present the first case of mucocutaneous leishmaniasis in Algeria, diagnosed in an immunocompetent 42-year-old man exhibiting an infiltrated and ulcerated plaque leading to macrocheilitis of the entire lower lip. He was a police officer who lived in a village in Ain El Hammam (Kabylie region, known as an active focus of zoonotic visceral leishmaniasis) without any history of travel for the previous 3 years. He suffered from cutaneous lesions for 22 months due to the misdiagnosis of a skin lesion resembling other diseases such as Crohn disease or sarcoidosis. A compilation of clinical, histopathological, parasitological, and molecular examinations revealed Leishmania infantum as the etiologic agent. The patient was treated with meglumine antimoniate, which resulted in the complete disappearance of the lesion 4 months after treatment.
Subject(s)
Antiprotozoal Agents , Leishmania infantum , Leishmaniasis, Mucocutaneous , Meglumine Antimoniate , Humans , Male , Adult , Algeria , Leishmaniasis, Mucocutaneous/drug therapy , Leishmaniasis, Mucocutaneous/diagnosis , Leishmaniasis, Mucocutaneous/parasitology , Antiprotozoal Agents/therapeutic use , Meglumine Antimoniate/therapeutic use , Leishmania infantum/isolation & purification , Meglumine/therapeutic use , Organometallic Compounds/therapeutic useABSTRACT
OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.