Comparison of 18F-MFBG PET/CT and 18F-FDG PET/CT Images of Metastatic Neuroblastoma.

ABSTRACT: Two children with neuroblastoma underwent tumor resection and postoperative chemotherapy. After treatment, they participated in a clinical trial and received 18F-MFBG and 18F-FDG PET/CT examinations. Although similar lesions were found in the 2 examinations, the uptake pattern was different. The lymph nodes and bone lesions had intense 18F-MFBG activity, whereas 18F-FDG uptake was not very impressive. The uptake of bone marrow by 18F-MFBG was significantly stronger than that by 18F-FDG. This case emphasizes that 18F-MFBG PET/CT is superior to 18F-FDG PET/CT in detecting the metastases of neuroblastoma.

Tc-99m-MIBI SPECT/CT imaging to diagnose secondary hyperparathyroidism after parathyroid forearm transplantation.

This article report a 40-year-old male patient who underwent total thyroidectomy and forearm auto-transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow-up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc-99m-MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels.

Advancing Alzheimer's research: Radiomics visualization of the default mode network in cerebral perfusion imaging.

OBJECTIVE: Alzheimer's disease, an irreversible neurological condition, demands timely diagnosis for effective clinical intervention. This study employs radiomics analysis to assess image features in default mode network cerebral perfusion imaging among individuals with cognitive impairment. METHODS: A radiomics analysis of cerebral perfusion imaging was conducted on 117 patients with cognitive impairment. They were divided into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest were employed to select and model image features, followed by logistic regression analysis of LASSO and Random Forest results. Diagnostic performance was assessed by calculating the area under the curve (AUC). RESULTS: In the training set, LASSO achieved AUC of 0.978, Random Forest had an AUC of 0.933. In the validation set, LASSO had AUC of 0.859, Random Forest had AUC of 0.986. By conducting Logistic Regression analysis in combination with LASSO and Random Forest, we identified a total of five radiomics features, with four related to morphology and one to textural features, originating from the medial prefrontal cortex and middle temporal gyrus. In the training set, Logistic Regression achieved AUC of 0.911, while in the validation set, it attained AUC of 0.925. CONCLUSION: The medial prefrontal cortex and middle temporal gyrus are the two brain regions within the default mode network that hold the highest significance for Alzheimer's disease diagnosis. Radiomics analysis contributes to the clinical assessment of Alzheimer's disease by delving into image data to extract deeper layers of information.

Managing spindle cell sarcoma with surgery and high-intensity focused ultrasound: A case report.

BACKGROUND: Undifferentiated pleomorphic sarcomas, also known as spindle cell sarcomas, are a relatively uncommon subtype of soft tissue sarcomas in clinical practice. CASE SUMMARY: We present a case report of a 69-year-old female patient who was diagnosed with undifferentiated spindle cell soft tissue sarcoma on her left thigh. Surgical excision was initially performed, but the patient experienced a local recurrence following multiple surgeries and radioactive particle implantations. High-intensity focused ultrasound (HIFU) was subsequently administered, resulting in complete ablation of the sarcoma without any significant complications other than bone damage at the treated site. However, approximately four months later, the patient experienced a broken lesion at the original location. After further diagnostic workup, the patient underwent additional surgery and is currently stable with a good quality of life. CONCLUSION: HIFU has shown positive outcomes in achieving local control of limb spindle cell sarcoma, making it an effective non-invasive treatment option.

Diagnosis of thyroid disease using deep convolutional neural network models applied to thyroid scintigraphy images: a multicenter study.

Objectives: The aim of this study was to improve the diagnostic performance of nuclear medicine physicians using a deep convolutional neural network (DCNN) model and validate the results with two multicenter datasets for thyroid disease by analyzing clinical single-photon emission computed tomography (SPECT) image data. Methods: In this multicenter retrospective study, 3194 SPECT thyroid images were collected for model training (n=2067), internal validation (n=514) and external validation (n=613). First, four pretrained DCNN models (AlexNet, ShuffleNetV2, MobileNetV3 and ResNet-34) for were tested multiple medical image classification of thyroid disease types (i.e., Graves' disease, subacute thyroiditis, thyroid tumor and normal thyroid). The best performing model was then subjected to fivefold cross-validation to further assess its performance, and the diagnostic performance of this model was compared with that of junior and senior nuclear medicine physicians. Finally, class-specific attentional regions were visualized with attention heatmaps using gradient-weighted class activation mapping. Results: Each of the four pretrained neural networks attained an overall accuracy of more than 0.85 for the classification of SPECT thyroid images. The improved ResNet-34 model performed best, with an accuracy of 0.944. For the internal validation set, the ResNet-34 model showed higher accuracy (p < 0.001) when compared to that of the senior nuclear medicine physician, with an improvement of nearly 10%. Our model achieved an overall accuracy of 0.931 for the external dataset, a significantly higher accuracy than that of the senior physician (0.931 vs. 0.868, p < 0.001). Conclusion: The DCNN-based model performed well in terms of diagnosing thyroid scintillation images. The DCNN model showed higher sensitivity and greater specificity in identifying Graves' disease, subacute thyroiditis, and thyroid tumors compared to those of nuclear medicine physicians, illustrating the feasibility of deep learning models to improve the diagnostic efficiency for assisting clinicians.

Imageological/Structural Study regarding the Improved Pharmacokinetics by 68Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer.

PMSA (prostate-specific membrane antigen) is currently the most significant target for diagnosing and treating PCa (prostate cancer). Herein, we reported a series 68Ga/177Lu-labeled multimer PSMA tracer conjugating with PEG chain, including [68Ga]Ga-DOTA-(1P-PEG4), [68Ga]Ga-DOTA-(2P-PEG0), [68Ga]Ga-DOTA-(2P-PEG4), and [68Ga]Ga/[177Lu]Lu-DOTA-(2P-PEG4)2, which showed an advantage of a multivalent effect and PEGylation to achieve higher tumor accumulation and faster kidney clearance. To figure out how structural optimizations based on a PSMA multimer and PEGylation influence the probe's tumor-targeting ability, biodistribution, and metabolism, we examined PSMA molecular probes' affinities to PC-3 PIP (PSMA-highly-expressed PC-3 cell line), and conducted pharmacokinetics analysis, biodistribution detection, small animal PET/CT, and SPECT/CT imaging. The results showed that PEG4 and PSMA dimer optimizations enhanced the probes' tumor-targeting ability in PC-3 PIP tumor-bearing mice models. Compared with the PSMA monomer, the PEGylated PSMA dimer reduced the elimination half-life in the blood and increased uptake in the tumor, and the biodistribution results were consistent with PET/CT imaging results. [68Ga]Ga-DOTA-(2P-PEG4)2 exhibited higher tumor-to-organ ratios. When labeled by lutetium-177, relatively high accumulation of DOTA-(2P-PEG4)2 was still detected in PC-3 PIP tumor-bearing mice models after 48 h, indicating its prolonged tumor retention time. Given the superiority in imaging, simple synthetic processes, and structural stability, DOTA-(2P-PEG4)2 is expected to be a promising tumor-targeting diagnostic molecular probe in future clinical practice.

Corrigendum: Effect of 131 I with and without artificial liver support system in patients with Graves' disease and severe liver dysfunction: A retrospective study.

[This corrects the article DOI: 10.3389/fendo.2022.1034374.].

SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis.

The so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, 99mTc-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative hepatoma, and then compared with 18F-FDG or 68Ga-FAPI-04 PET/CT. The radio-labeling rate of 99mTc-HYNIC-FAPI-04 was greater than 90%, and the radiochemical purity was >99% after purification with sep-pak C18 column. In vitro cell uptake experiments of 99mTc-HYNIC-FAPI-04 showed good FAP binding specificity, and the cellular uptake significantly decreased when blocked by DOTA-FAPI-04, reflecting the similar targeting mechanism of HYNIC-FAPI-04 and DOTA-FAPI-04. SPECT/CT imaging showed that U87MG tumor was distinguishable and of a high uptake of 99mTc-HYNIC-FAPI-04 (2.67 ± 0.35 %ID/mL at 1.5 h post injection (h P.I.), while tumor signal of FAP-negative HUH-7 was as low as 0.34 ± 0.06 %ID/mL. At 5 h P.I., U87MG tumor was still distinguishable (1.81 ± 0.20 %ID/mL). In comparison, although U87MG tumor was of obvious 68Ga-FAPI-04 uptake and clearly visible at 1 h P.I., the tumorous radioactive signals were fuzzy at 1.5 h P.I. 99mTc-HYNIC-FAPI-04 specifically bound to FAP-positive tumors and qualified with the ability of evaluating tumor fibrosis over longer time windows.

Poly (lactic-co-glycolic acid)-encapsulated iodine-131 nanoparticles fabricated with rhTSH induce apoptosis and immobilization of thyroid cancer cells.

Background: Aggressive thyroid carcinoma (ATC) usually loses radioiodine avidity to iodine-131 (131I) due to the downregulation of sodium/iodide symporter (NIS). The expression of thyroid stimulating hormone receptor (TSHR) is more persistent than NIS and the administration of recombinant human thyroid stimulating hormone (rhTSH) promotes de novo NIS synthesis. Hence, exploring methods integrating 131I with rhTSH might be a feasible therapeutic strategy for selective delivery of 131I into thyroid cancer to fortify the effect of radioiodine ablation. Methods: The 131I, poly (lactic-co-glycolic acid) (PLGA) and rhTSH were used to synthesize of the 131I-PLGA-rhTSH nanoparticles. The characteristics of the 131I-PLGA-rhTSH nanoparticles was determined using a light microscopy, scanning electron microscopy (SEM), autoradiography and immunofluorescence (IF) staining. The diameter of the 131I-PLGA-rhTSH nanoparticles was measured with a Mastersizer 3000, and the encapsulation efficiency (EF) of 131I in 131I-PLGA-rhTSH nanoparticles and the radioactivity of a single nanoparticle were determined. Then, the mouse tumor xenograft model was established, and the biodistribution and effect of 131I-PLGA-rhTSH nanoparticles on apoptosis of thyroid cance cells were investigated in vivo. Thereafter, the role of 131I-PLGA-rhTSH nanoparticles in cell viability using cell counting kit-8 and lactate dehydrogenase (LDH) release assays. Subsequently, the underlying mechanism of 131I-PLGA-rhTSH nanoparticles in reducing cell viability was assessed using immunostaining, boyden invasion assays and phalloidin staining. Results: Our results showed that the method of developing nanoparticles-encapsulated 131I using poly (lactic-co-glycolic acid) (PLGA) and modified with rhTSH (131I-PLGA-rhTSH), was a feasible avenue for the integration of 131I and rhTSH. Meanwhile, the encapsulation efficiency (EF) of 131I-PLGA-rhTSH nanoparticles was approximately 60%, and the radioactivity of a single nanoparticle was about 1.1×10-2 Bq. Meanwhile, the 131I-PLGA-rhTSH nanoparticles were selectively delivered into, gradually enriched and slowly downregulated in xenograft tumor after the administration of 131I-PLGA-rhTSH nanoparticles through tail vein in mouse tumor xenograft model. Thereafter, the tumor weight was significantly reduced after the administration of 131I-PLGA-rhTSH nanoparticles. Subsequently, the application of 131I-PLGA-rhTSH nanoparticles facilitated apoptosis and attenuated immobilization via inhibiting F-actin assembling of FTC-133 cells. Conclusion: The present study develops a suitable approach integrating 131I and rhTSH, and this strategy is a feasible regimen enhancing the effect of radioiodine ablation for the treatment of thyroid cancer.

Effect of 131I with and without artificial liver support system in patients with Graves' disease and severe liver dysfunction: A retrospective study.

Objective: Treatment decision-making in Graves' disease (GD) with severe liver dysfunction (LD) is a clinical challenge. This research was carried out to evaluate the effect of radioiodine (131I) with or without an artificial liver support system (ALSS) in GD patients with severe LD. Methods: In total, 45 patients diagnosed with GD and severe LD were enrolled and allocated to two groups: patients treated with 131I alone (n=30) (Group A)and patients by a combination of 131I and ALSS (n=15)(Group B). Liver function, thyroid hormone concentrations, therapeutic efficacy, and the cost of treatment were compared between the two groups. Results: Thyroid hormone concentrations were lower 2 weeks after 131I treatment, but no deterioration in liver function was identified. There was no statistically significant difference in the treatment efficacy between the two groups. The hospital stay, total cost, and daily cost were lower in patients treated with 131I alone than in those treated with 131I and an ALSS (p<0.05). Conclusion: The key point of treating GD patients with severe LD is to control the GD.131I is recommended as an effective and safe and should be applied as soon as possible once the diagnosis is clarified; however, when used in combination with an ALSS, there was no substantial improvement in therapeutic efficacy.

Analysis of factors influencing the clinical outcome after surgery and 131I therapy in patients with moderate-risk thyroid papillary carcinoma.

Purpose: Generally, the prognosis for papillary thyroid cancer (PTC) is favorable. However, the moderate risk involved warrants further evaluation. Hence, we investigated the clinical outcomes in patients with moderate-risk PTC following surgery and the first 131I therapy, as well as the relevant factors that influence the therapeutic efficacy. Methods: Retrospective analyses of 175 patients with medium-risk PTC who visited the Second Affiliated Hospital of Chongqing Medical University from September 2017 to April 2019 were conducted. In according with the 2015 American Thyroid Association (ATA) guideline treatment response evaluation system, the patients were categorized into the following groups: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structurally incomplete response (SIR), of which IDR, BIR, and SIR were collectively referred to as the NER group. To compare the general clinical features between the 2 groups of patients, 2 independent samples t-tests, χ2 test, and Mann-Whitney U-test were performed, followed by multivariate logistic regression analyses. With reference to the receiver operating characteristic (ROC) curve, the predicted value of ps-Tg to ER was evaluated, and the best cut-off value was determined. The subgroups with BRAFV600E test results were analyzed by χ2 test only. Results: The treatment responses of 123 patients were ER, while those of 52 patients were NER. The differences in the maximum tumor diameter (U = 2495.50), the amount of metastatic lymph nodes (U = 2313.50), the size of metastatic lymph node (U = 2113.50), the metastatic lymph node ratio (U = 2111.50), metastatic lymph node location (χ2 = 9.20), and ps-Tg level (U = 1011.00) were statistically significant. Multivariate regression analysis revealed that ps-Tg (OR = 1.209, 95% CI: 1.120-1.305) was an independent variable affecting ER. The cut-off value of ps-Tg for predicting ER was 6.915 ug/L, while its sensitivity and specificity were 69.2% and 89.4%, respectively. Conclusions: Patients with smaller tumor size, fewer lymph nodes, lower metastatic lymph node ratio, metastatic lymph nodes in the central region, smaller lymph node size, and ps-Tg <6.915 ug/L demonstrated better therapeutic effects after the initial treatment.

Dual-sonosensitizer loaded phase-transition nanoparticles with tumor-targeting for synergistically enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) is a fast-growing therapy activated by using ultrasound to initiate a catalytic reaction of sensitizing agents and kill tumor cells through producing reactive oxygen species (ROS). Both sinoporphyrin sodium (DVDMS) and IR780 are preeminent sonosensitizers and have been used in SDT alone. In this study, tumor targeting multifunctional composite nanoparticles (DVDMS@IR780@PFP@PLGA, DIPP-NPs) were synthesized by encapsulating DVDMS, IR780 and perfluoropentane (PFP) to synergistically enhance SDT and achieve imaging of tumors. The loaded IR780 is regarded as a "navigator" to accurately identify and target tumor cells/tissues. DVDMS and IR780 not only can realize the directed SDT, but also can perform photoacoustic (PA) imaging. PFP plays its role in enhancing the ultrasound (US) imaging. Generally, DIPP-NPs not only have an obvious synergistic anti-tumor effect, but also are able to carry out dual-mode imaging, which paves a promising way for tumor therapy.

Iron(II) phthalocyanine Loaded and AS1411 Aptamer Targeting Nanoparticles: A Nanocomplex for Dual Modal Imaging and Photothermal Therapy of Breast Cancer.

PURPOSE: A multi-functional nanoplatform with diagnostic imaging and targeted treatment functions has aroused much interest in the nanomedical research field and has been paid more attention in the field of tumor diagnosis and treatment. However, some existing nano-contrast agents have encountered difficulties in different aspects during clinical promotion, such as complicated preparation process and low specificity. Therefore, it is urgent to find a nanocomplex with good targeting effect, high biocompatibility and significant therapeutic effect for the integration of diagnosis and treatment and clinical transformation. MATERIALS AND METHODS: Nanoparticles (NPs) targeting breast cancer were synthesized by phacoemulsification which had liquid fluorocarbon perfluoropentane(PFP) in the core and were loaded with Iron(II) phthalocyanine (FePc) on the shell. The aptamer (APT) AS1411 was outside the shell used as a molecular probe. Basic characterization and targeting abilities of the NPs were tested, and their cytotoxicity and biological safety in vivo were evaluated through CCK-8 assay and blood bio-chemical analysis. The photoacoustic (PA) and ultrasound (US) imaging system were used to assess the effects of AS1411-PLGA@FePc@PFP (A-FP NPs) as dual modal contrast agent in vitro and in vivo. The effects of photothermal therapy (PTT) in vitro and in vivo were evaluated through MCF-7 cells and tumor-bearing nude mouse models. RESULTS: A-FP NPs, with good stability, great biocompatibility and low toxicity, were of 201.87 ± 1.60 nm in diameter, and have an active targeting effect on breast cancer cells and tissues. With the help of PA/US imaging, it was proved to be an excellent dual modal contrast agent for diagnosis and guidance of targeted therapy. Meanwhile, it can heat up under near-infrared (NIR) laser irradiation and has achieved obvious antitumor effect both in vitro and in vivo experiments. CONCLUSION: As a kind of nanomedicine, A-FP NPs can be used in the integration of diagnosis and treatment. The treatment effects and biocompatibility in vivo may provide new thoughts in the clinical transformation of nanomedicine and early diagnosis and treatment of breast cancer.

Ultrasound targeted microbubble destruction promotes angiogenesis and heart function by inducing myocardial microenvironment change.

The myocardial microenvironment plays a decisive role in the survival, migration and differentiation of stem cells. We studied myocardial micro-environmental changes induced by ultrasound-targeted microbubble destruction (UTMD) and their influence on the transplantation of mesenchymal stem cells (MSCs). Various intensities of ultrasound were applied to the anterior chest in canines with myocardial infarction after intravenous injection of microbubbles. The expression of cytokines and adhesion molecules in the infarcted area of the myocardium was detected after three sessions of UTMD in 1 wk. Real-time quantitative reverse transcription polymerase chain reaction (RTQ-PCR) showed that the expression of vascular cell adhesion molecule-1 (VCAM-1), stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGF) in the 1.5 W/cm(2) and 1 W/cm(2) groups was markedly increased compared with the 0.5 W/cm(2) or the control groups (3.8- to 4.7-fold, p < 0.01), and the expression of interleukin-1ß (IL-1ß) in the 1.5 W/cm(2) group was increased twofold over the 1.0 W/cm(2) group, whereas the 0.5 W/cm(2) group experienced no significant changes. UTMD at 1.0 W/cm(2) was performed as previously described before mesenchymal stem cell (MSC) transplantation. Myocardial perfusion, angiogenesis and heart function were investigated before and 1 month after MSC transplantation. Coronary angiography and 99mTc-tetrofosmin scintigraphy revealed that myocardial perfusion was markedly improved after UTMD + MSCs treatment (p < 0.05). At echocardiographic analysis, heart function and the wall motion score index were significantly improved by UTMD + MSCs treatment compared with MSCs or UTMD alone and the control. In a canine model of myocardial infarction, therapeutic effects were markedly enhanced by MSC transplantation after the myocardial micro-environmental changes induced by UTMD; therefore, this novel method may be useful as an efficient approach for cellular therapy.

Combined effects of all-trans-retinoic acid and trichostatin A on the induction of differentiation of thyroid carcinoma cells.

BACKGROUND AND OBJECTIVE: The effectiveness rate of all-trans-retinoic acid (RA) is only about 30% in the clinical application of inducing thyroid carcinoma differentiation. In addition, there are severe toxic side effects, which limit its clinical application. Phase I-III clinical studies have been conducted on the combined application of two or more kinds of inductors in tumors. Nevertheless, the combination of RA with histone deacetylase inhibitors is rarely reported. This article studied the effects of differentiation for papillary thyroid carcinoma and follicular thyroid carcinoma cell lines induced by RA combined with trichostatin A (TSA), enhancing the effect of induction, while reducing the toxic side effects of a single drug, to provide a theoretical basis for preclinical trials. METHODS: After incubation with RA combined with TSA, K1 and FTC-133 were grouped into Group 1 (RA 10(-4) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 2 (RA 1 x 10(-4) mol/L plus TSA 3.31 x 10(-7) mol/L), Group 3 (RA 10(-5) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 4 (RA 1 x10(-5) mol/L plus TSA 3.31 x 10(-7) mol/L) by four varied concentrations and three time points (12 h, 24 h, and 48 h). The cell proliferation, conformation, toxic effect, and induced differentiation on K1 and FTC-133 cell lines were studied microscopically with hematoxylin-eosin (HE) to observe cell quantity and morphology, methyl-thiazolyl-tetrazolium (MTT) to calculate cell survival rates, and electrochemiluminescence analysis measuring in vitro thyroglobulin (Tg) levels. RESULTS: The research showed that K1 and FTC-133 cells had cell spacing increases, with an outer edge of smooth, nuclear chromatin condensation after RA combined TSA. Survival rate were assessed by an analysis of variance (ANOVA) by concentration and time point, F values of K1 and FTC-133 were 23.52 and 170.14, and 57.09 and 224.35, respectively. There were significant differences for both cells (P < 0.01). The SNK analysis indicated that survival rates were in the order of Group 2 < Group 1 < Group 4 < Group 3. Tg was also assessed by ANOVA, F values of K1 were 69.63 and 101.07, and F values of FTC-133 were 79.77 and 81.72 (P < 0.01). Group 1 was compared with Group 3 of K1 and FTC-133 by the least significant difference (LSD) method, and there was no statistical difference between the two group (P = 0.06, 0.2, respectively; P > 0.05), yet a significant difference was seen between the other Groups. CONCLUSIONS: Lower concentrations of RA combined with lower concentrations of TSA have both inhibited cell proliferation, decreased toxicity of the drugs, and increased the effect of K1 and FTC-133 cell differentiation. The mechanism of action may be that TSA has pretranscription DNA regulation and that RA has posttranscriptional signal regulation to enhance the effects of inhibited proliferation and differentiation of cells by transcription systems.