18F-Radiolabeling and Evaluation of an AMD3465 Derivative for PET Imaging of CXCR4 in a Mouse Breast Tumor Model.

The exploration of pharmaceutically active agents and positron emission tomography (PET) tracers targeting CXCR4 has been a focal point in cancer research given its pivotal role in the development and progression of various cancers. While significant strides have been made in PET imaging with radiometal-labeled tracers, the landscape of 18F-labeled small molecule tracers remains relatively limited. Herein, we introduce a novel and promising derivative, [18F]SFB-AMD3465, as a targeted PET tracer for CXCR4. The compound was synthesized by modifying the pyridine ring of AMD3465, which was subsequently labeled with 18F using [18F]SFB. The study provides comprehensive insights into the design, synthesis, and biological evaluation of [18F]SFB-AMD3465. In vitro and in vivo assessments demonstrated the CXCR4-dependent, specific, and sensitive uptake of [18F]SFB-AMD3465 in the CXCR4-overexpressing 4T1 cell line and the corresponding xenograft-bearing mouse model. These findings contribute to bridging the gap in 18F-labeled PET tracers for CXCR4 and underscore the potential of [18F]SFB-AMD3465 as a PET radiotracer for in vivo CXCR4 imaging.

[99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of 227 consecutive patients with newly diagnosed prostate cancer: a 5-year monocentric retrospective study.

Purpose: The purpose of this study was to assess the effectiveness of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of patients with newly diagnosed PCa. Methods: A retrospective analysis was conducted on 227 consecutive patients who underwent [99mTc]Tc-HYNIC-ALUG SPECT/CT imaging for the primary staging of newly diagnosed PCa. The presence and location of PSMA-positive lesions were determined, and the maximum standardized uptake values (SUVmax) of the primary prostate tumor were also measured. The metastatic findings and SUVmax were stratified according to International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) levels, and D'Amico classification. Furthermore, the [99mTc]Tc-HYNIC-ALUG SPECT/CT findings were compared to the histopathological findings in patients who had undergone radical prostatectomy with pelvic lymph node dissection (PLND). Results: Of the 227 patients, 92.1% (209/227) had positive [99mTc]Tc-HYNIC-ALUG SPECT/CT findings. Advanced disease was detected in 38.8% (88/227) of the patients and was positively correlated with increasing ISUP grade and PSA levels. Lymph node metastases (both pelvic and extrapelvic), bone metastases, and visceral metastases were detected in 30.0% (68/227), 25.6% (58/227), and 3.1% (7/227) of the patients, respectively. For the 129 patients who underwent radical prostatectomy with PLND, the sensitivity of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the evaluation of PCa was 90.7% (117/129). The sensitivity, specificity, accuracy, and positive and negative predictive values for detecting pelvic lymph node metastases on [99mTc]Tc-HYNIC-ALUG SPECT/CT were 23.5% (12/51), 93.6% (73/78), 65.9% (85/129), 70.6% (12/17), and 65.2% (73/112), respectively. Among the 209 patients with PSMA-avid primary prostate disease, the SUVmax of the primary prostate tumor was significantly associated with ISUP grade (p<0.0001), PSA levels (p<0.0001), D'Amico classification (p<0.0001), and advanced disease (p<0.0001). Receiver operating characteristic (ROC) analysis revealed that a PSA level >19.8 ng/ml and SUVmax of the primary prostate tumor >7.4 had a sensitivity of 71.6% and 71.6% and specificity of 76.9% and 82.6%, respectively, for detecting metastatic disease. Conclusions: [99mTc]Tc-HYNIC-ALUG SPECT/CT emerges as a valuable imaging tool for the initial staging of newly diagnosed PCa. The presence of advanced disease and the SUVmax of the primary prostate tumor were positively correlated with ISUP grade and PSA levels.

Kirigami-Structured, Low-Impedance, and Skin-Conformal Electronics for Long-Term Biopotential Monitoring and Human-Machine Interfaces.

Epidermal dry electrodes with high skin-compliant stretchability, low bioelectric interfacial impedance, and long-term reliability are crucial for biopotential signal recording and human-machine interaction. However, incorporating these essential characteristics into dry electrodes remains a challenge. Here, a skin-conformal dry electrode is developed by encapsulating kirigami-structured poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)/polyvinyl alcohol (PVA)/silver nanowires (Ag NWs) film with ultrathin polyurethane (PU) tape. This Kirigami-structured PEDOT:PSS/PVA/Ag NWs/PU epidermal electrode exhibits a low sheet resistance (≈3.9 Ω sq-1 ), large skin-compliant stretchability (>100%), low interfacial impedance (≈27.41 kΩ at 100 Hz and ≈59.76 kΩ at 10 Hz), and sufficient mechanoelectrical stability. This enhanced performance is attributed to the synergistic effects of ionic/electronic current from PEDOT:PSS/Ag NWs dual conductive network, Kirigami structure, and unique encapsulation. Compared with the existing dry electrodes or standard gel electrodes, the as-prepared electrodes possess lower interfacial impedance and noise in various conditions (e.g., sweat, wet, and movement), indicating superior water/motion-interference resistance. Moreover, they can acquire high-quality biopotential signals even after water rinsing and ultrasonic cleaning. These outstanding advantages enable the Kirigami-structured PEDOT:PSS/PVA/Ag NWs/PU electrodes to effectively monitor human motions in real-time and record epidermal biopotential signals, such as electrocardiogram, electromyogram, and electrooculogram under various conditions, and control external electronics, thereby facilitating human-machine interactions.

Analysis of the clinical factors affecting excellent response of Iodine-131 treatment for pulmonary metastases from differentiated thyroid cancer.

Background: Iodiene-131 (131I) treatment is the primary therapeutic approach for imaging 131I-avid pulmonary metastases. The response to radioiodine (RAI) treatment is an important prognostic factor in patients with pulmonary metastases from differentiated thyroid cancer (DTC). Patients who achieve an excellent response (ER) to 131I treatment show significantly reduced disease-related mortality. This study aimed to retrospectively analyse the clinical data and therapeutic effects of 131I treatment in patients with DTC and pulmonary metastases and to screen out the clinical factors affecting ER. Materials and methods: The study included a total of 75 patients with exclusively Iodine-131 avid (131I-avid) pulmonary metastases who underwent 131I treatment. Relevant clinical data for these patients were collected. Following treatment, the status of DTC metastatic lesions was categorized as follows: excellent response (ER), biochemical incomplete response (BIR), structural incomplete response (SIR), or indeterminate response (IDR). Gender, age at diagnosis, pathological type, stages (TNM), stimulated thyroglobulin (sTg) value before initial 131I treatment, metastatic nodule size, and type of post-treatment whole body scan (Rx-WBS) were recorded. Mono-factor analysis and binary logistic regression analyses were used to identify the factors that might affect the ER in DTC pulmonary metastases. The receiver operating characteristic (ROC) curve of the sTg value was used to predict the ER of 131I treatment. Results: All 75 patients with exclusively 131I-avid pulmonary metastases received 131I treatment and underwent follow-up. Out of the 75 patients, 26 achieved ER, resulting in an excellent response rate of 34.7 % (26/75). Among them, 25 (25/26, 96.2 %) achieved an ER after undergoing two rounds of 131I treatment. Binary logistic regression analysis showed that the factors influencing DTC pulmonary metastases excellent response were lower sTg levels [odds ratio (OR) = 0.998, P < 0.001], micronodular metastases (OR = 0.349, P = 0.001) and focal distribution on Rx-WBS imaging (OR = 0.113, P = 0.001). The area under the ROC curve for sTg value predicting ER was 0.876, and the cut-off value was 26.84 ng/mL, with a sensitivity and specificity of 87.9 % and 80.3 %, respectively. Conclusions: 131I treatment is effective for 131I-avid pulmonary metastases of DTC. Some patients who underwent 131I treatment achieved ER. Most patients with ER were obtained after two rounds of 131I treatments. Patients with sTg values before initial 131I treatment lower than 26.84 ng/mL, micronodular metastases, and focal distribution on Rx-WBS imaging were more likely to achieve ER.

Integrin αvß3 and EGFR dual-targeted [64Cu]Cu-NOTA-RGD-GE11 heterodimer for PET imaging in pancreatic cancer mouse model.

PURPOSE: Radiolabeled heterodimeric peptide has emerged as a highly promising targeting strategy for PET imaging due to their superior properties. RGD and GE11 are two peptides binding to receptor integrin αvß3 and EGFR, respectively, which both overexpress in many different types of tumors. This study focuses on the synthesis and evaluation of a RGD and GE11-containing heterodimeric radiotracer [64Cu]Cu-NOTA-RGD-GE11 for PET imaging of tumors that simultaneously overexpress integrin αvß3 and EGFR. PROCEDURES: [64Cu]Cu-NOTA-RGD-GE11 was prepared by the conjugation of RGD-PEG4-NOTA-N3 and GE11-PEG4-BCN via metal-free click chemistry, followed by radiolabeling with 64Cu. Cell uptake and efflux studies, saturation binding assay, the animal PET/CT and biodistribution studies were conducted to characterize the biological properties of [64Cu]Cu-NOTA-RGD-GE11. RESULTS: [64Cu]Cu-NOTA-RGD-GE11 was synthesized with a radiochemical purity of >97 % and molar activity of 23 GBq/µmol at the end of synthesis. [64Cu]Cu-NOTA-RGD-GE11 showed moderate hydrophilicity, good stability in mouse serum and high specific uptake by the human pancreatic cancer cell line (BxPC3) in the in vitro studies. Compared to the two monomeric counterparts [64Cu]Cu-NOTA-RGD and [64Cu]Cu-NOTA-GE11, [64Cu]Cu-NOTA-RGD-GE11 demonstrated significantly improved tumor uptakes (e.g. 4.63 ± 0.25 %ID/g vs 1.24 ± 0.18 %ID/g and 0.77 ± 0.13 %ID/g, 2 h after injection, p < 0.05) in the subsequent in vivo evaluation in mice bearing BxPC3 xenograft. Tumor uptake could be blocked in the presence of both non-radioactive c(RGDyK) and GE11 peptides, indicating good tumor specificity of [64Cu]Cu-NOTA-RGD-GE11 in vivo. CONCLUSION: The results suggested that the as-developed [64Cu]Cu-NOTA-RGD-GE11 could serve as a potential PET tracer for the noninvasive imaging of integrin αvß3 and EGFR expression in tumors.

Diagnostic accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting osteomalacia-associated tumors.

Objectives: Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder characterized by hypophosphatemia resulting from tumor-secreted fibroblast growth factor-23 (FGF23). Surgical resection of the culprit TIO is the first choice of treatment. However, TIO is difficult to detect with conventional diagnostic tools due to its small size and variable location in the body. Somatostatin receptor scintigraphy (SSR) has recently emerged as a functional molecular imaging choice for TIO detection and localization. This research was undertaken to evaluate the efficacy of 99mTc-labeled hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) SPECT/CT in detecting TIO. Methods: 99mTc-HYNIC-TOC SPECT/CT and the available clinical data of 25 patients with suspected TIO were analyzed retrospectively. The 99mTc-HYNIC-TOC SPECT/CT findings were compared with the post-surgical pathology diagnosis and clinical follow-up results. Results: Using 99mTc-HYNIC-TOC SPECT/CT, suspicious tumors were found in 18 of the 25 patients, and 15 of them underwent surgical resection. The post-operative pathology confirmed a TIO in those 13 patients whose symptoms and biochemical anomalies gradually resolved after the surgery. The remaining five patients were finally considered false positives. Moreover, the 99mTc-HYNIC-TOC SPECT/CT results were negative in seven patients, with six patients being true negative (4 patients were diagnosed with acquired Fanconi syndrome and 2 patients responded well to conservative therapy) and one being false negative. Therefore, the sensitivity and specificity values of 99mTc-HYNIC-TOC SPECT/CT in the evaluation of TIO were 92.9% (13/14) and 54.5% (6/11), respectively. The overall accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting TIO was 76.0% (19/25). Conclusions: The 99mTc-HYNIC-TOC SPECT/CT is an accurate imaging modality for locating culprit tumors in TIO.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

Silencing circ_0000644 inhibits papillary thyroid cancer cell malignancy by combining with miR-671-5p to release the inhibition on ANXA2.

BACKGROUND: Papillary thyroid cancer (PTC) is life-threatening due to its malignant progression. Considerable evidence demonstrates that circular RNA (circRNA) regulates PTC development. This study aims to explore the mechanism of circ_0000644 modulating PTC malignant progression. METHODS: The RNA levels of circ_0000644, microRNA-671-5p (miR-671-5p) and annexin A2 (ANXA2) were detected by quantitative real-time polymerase chain reaction. Western blot was performed to check protein expression. Cell proliferation and cell apoptosis were investigated by 5-ethynyl-29-deoxyuridine and flow cytometry. Angiogenic capacity, migration and invasion were analyzed by tube formation assay and transwell assay. The interaction between miR-671-5p and circ_0000644 or ANXA2 was identified by dual-luciferase reporter assay. Xenograft mouse model assay was performed to analyze the effect of circ_0000644 on tumor formation in vivo. RESULTS: Circ_0000644 and ANXA2 expression was significantly upregulated, while miR-671-5p was downregulated in PTC tissues and cells when compared with control groups. Circ_0000644 knockdown inhibited PTC cell proliferation, tube formation, migration, and invasion, but induced apoptosis in vitro. Moreover, circ_0000644 knockdown led to delayed tumorigenesis in vivo. In addition, circ_0000644 acted as a miR-671-5p sponge and mediated PTC cell tumor properties through miR-671-5p. ANXA2 was identified as a target gene of miR-671-5p, and its overexpression relieved miR-671-5p-induced effects in PTC cells. Furthermore, circ_0000644 depletion inhibited ANXA2 production by combining with miR-671-5p. CONCLUSION: Circ_0000644 depletion repressed PTC cell tumor properties through the miR-671-5p/ANXA2 axis.

Diagnostic performance of 99mTc-HYNIC-PSMA SPECT/CT for biochemically recurrent prostate cancer after radical prostatectomy.

Objectives: 99mTc-HYNIC-PSMA is a novel technetium-99m-labeled small-molecule inhibitor of prostate-specific membrane antigen (PSMA) for detection of prostate cancer. The present study investigated the diagnostic yield of 99mTc-HYNIC-PSMA Single photon emission computed tomography (SPECT)/CT in 147 patients with biochemically recurrent prostate cancer after radical prostatectomy. Methods: 147 patients with biochemical relapse after radical prostatectomy were finally eligible for this retrospective analysis. The median prostate-specific antigen (PSA) level was 8.26 ng/mL (range, 0.22-187.40 ng/mL). Of the 147 patients, 72 patients received androgen deprivation therapy (ADT) at least 6 months before the 99mTc-HYNIC-PSMA SPECT/CT. All patients underwent planar whole-body scans and subsequent SPECT/CT of the thoracic and abdominal regions after intravenous injection of 705 ± 70 MBq of 99mTc-HYNIC-PSMA. Images were evaluated for the presence and location of PSMA-positive lesions, in which SUVmax were also measured. Detection rates were stratified according to PSA levels, ADT and Gleason scores. The relationships between SUVmax and clinical characteristics were analyzed using univariate and multivariable linear regression models for patients with positive findings. Results: Of the 147 patients, 99mTc-HYNIC-PSMA SPECT/CT revealed at least one positive lesion in 118 patients with a high detection rate (80.3%). The detection rates were 48.6% (17/35), 85.1% (40/47), 92.1% (35/38), and 96.3% (26/27) at PSA levels of greater than 0.2 to 2, greater than 2 to 5, greater than 5 to 10, and greater than 10 ng/mL, respectively. PSMA SPECT/CT indicated local recurrence, lymph node metastases, bone metastases, and visceral metastases in 14 (9.5%), 73 (49.7%), 48 (32.7%) and 3 (2.0%) patients. The detection rates of local recurrence and metastasis increased with increasing PSA levels. The detection rate was higher in patients treated with ADT than those without (90.3% vs. 70.7%; P =0.0029). In patients with Gleason scores ≥8, detection rate was slightly higher than those with ≤7 (81.7% vs. 78.5%), but not statistically significant (P = 0.6265). Multivariable linear regression analysis showed a significant correlation of PSA levels and ADT with SUVmax (P=0.0005 and P=0.0397). Conclusions: 99mTc-HYNIC-PSMA SPECT/CT offers high detection rates for biochemically recurrent prostate cancer after radical prostatectomy. The detection rate and SUVmax were positively correlated with PSA levels and ADT.

The predictive value of total-body PET/CT in non-small cell lung cancer for the PD-L1 high expression.

Purpose: Total-body positron emission tomography/computed tomography (PET/CT) provides faster scanning speed, higher image quality, and lower injected dose. To compensate for the shortcomings of the maximum standard uptake value (SUVmax), we aimed to normalize the values of PET parameters using liver and blood pool SUV (SUR-L and SUR-BP) to predict programmed cell death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients. Materials and methods: A total of 138 (104 adenocarcinoma and 34 squamous cell carcinoma) primary diagnosed NSCLC patients who underwent 18F-FDG-PET/CT imaging were analyzed retrospectively. Immunohistochemistry (IHC) analysis was performed for PD-L1 expression on tumor cells and tumor-infiltrating immune cells with 22C3 antibody. Positive PD-L1 expression was defined as tumor cells no less than 50% or tumor-infiltrating immune cells no less than 10%. The relationships between PD-L1 expression and PET parameters (SUVmax, SUR-L, and SUR-BP) and clinical variables were analyzed. Statistical analysis included χ2 test, receiver operating characteristic (ROC), and binary logistic regression. Results: There were 36 patients (26%) expressing PD-L1 positively. Gender, smoking history, Ki-67, and histologic subtype were related factors. SUVmax, SUR-L, and SUR-BP were significantly higher in the positive subset than those in the negative subset. Among them, the area under the curve (AUC) of SUR-L on the ROC curve was the biggest one. In NSCLC patients, the best cutoff value of SUR-L for PD-L1-positive expression was 4.84 (AUC = 0.702, P = 0.000, sensitivity = 83.3%, specificity = 54.9%). Multivariate analysis confirmed that age and SUR-L were correlated factors in adenocarcinoma (ADC) patients. Conclusion: SUVmax, SUR-L, and SUR-BP had utility in predicting PD-L1 high expression, and SUR-L was the most reliable parameter. PET/CT can offer reference to screen patients for first-line atezolizumab therapy.

A redox-triggered C-centered free radicals nanogenerator for self-enhanced magnetic resonance imaging and chemodynamic therapy.

Current chemodynamic therapy (CDT) has been restricted by the requirement of strongly acidic conditions, insufficient endogenous H2O2 and upregulated cellular antioxidant defense. To overcome these obstacles, the carrier-free Fe(III)-ART nanoparticle is developed via coordination driven self-assembly of Fe3+ and hydrolyzed ART and evaluated as a redox-triggered C-centered free radicals nanogenerator for self-enhanced magnetic resonance imaging and chemodynamic therapy. The carrier-free Fe(III)-ART NPs can be triggered by intracellular GSH to release ART and Fe3+, which is further reduced to Fe2+ that catalyzed the endoperoxide of ART to generate C-centered free radicals. Notably, unlike current CDT, such a free radical generation process is without reliance on pH or endogenous H2O2. Meanwhile, the concurrent GSH depletion can diminish the antioxidation of tumors and enhance CDT. The C-centered free radicals-mediated apoptosis and GSH depletion-induced ferrotosis act in synergy, leading to potent tumor growth inhibition and superior anticancer efficacy in vitro and in vivo. Moreover, Fe(III)-ART NPs exhibit redox-triggered T2 relaxivity and contribute to activatable MRI-guided CDT. The development of biodegradable Fe(III)-ART NPs with superior anticancer efficacy, favorable pharmacokinetics and good biocompatibility provides a promising strategy to break through the bottlenecks of traditional CDT and greatly promotes the development of next-generation cancer theranostics.

Nuclear Imaging of Glucose Metabolism: Beyond 18F-FDG.

Glucose homeostasis plays a key role in numerous fundamental aspects of life, and its dysregulation is associated with many important diseases such as cancer. The atypical glucose metabolic phenomenon, known as the Warburg effect, has been recognized as a hallmark of cancer and serves as a promising target for tumor specific imaging. At present, 2-deoxy-2-[18F]fluoro-glucose (18F-FDG)-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for this purpose. The powerful impact of 18F-FDG has prompted intensive research efforts into other glucose-based radiopharmaceuticals for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging. Currently, glucose and its analogues have been labeled with various radionuclides such as 99mTc, 111In, 18F, 68Ga, and 64Cu and have been successfully investigated for tumor metabolic imaging in many preclinical studies. Moreover, 99mTc-ECDG has advanced into its early clinical trials and brings a new era of tumor imaging beyond 18F-FDG. In this review, preclinical and early clinical development of glucose-based radiopharmaceuticals for tumor metabolic imaging will be summarized.

A combined study of 18F-FDG PET-CT and fMRI for assessing resting cerebral function in patients with major depressive disorder.

The present study investigated changes in the regional cerebral metabolic rates of glucose uptake (rCMRglc) using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and regional homogeneity (ReHo), together with resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), in patients with major depressive disorder (MDD). In total, 18 patients with untreated MDD and 17 healthy control subjects underwent 18F-FDG PET and BOLD-fMRI scanning. The MDD patients' cerebral changes, measured as rCMRglc and ReHo values, were mapped and statistically analyzed. Compared with the control group, the patients with MDD had a decreased rCMRglc in the bilateral superior, middle and inferior frontal gyrus, in the bilateral superior and middle temporal gyrus, in the bilateral anterior cingulate cortex, in the bilateral putamen and caudate, and in the left pallidum, but an increased rCMRglc in the bilateral hippocampus and left thalamus. The ReHo values in the patient group were decreased in the bilateral superior and middle frontal gyrus, left pallidum, bilateral putamen and left anterior cingulate cortex, but increased in the right hippocampus and thalamus. No statistically significant differences were identified between decreased metabolism and ReHo brain regions of MDD patients (χ2=9.16; P=0.90) and between increased metabolism and ReHo brain regions (χ2=3.96; P=0.27), when comparing activated brain regions of PET and MRI. The standardized uptake values (SUV) of the bilateral superior, middle and inferior frontal gyrus, bilateral superior and middle temporal gyrus, bilateral putamen, the left caudate and pallidum, the left anterior cingulate cortex, and the bilateral hippocampus and thalamus were correlated with the ReHo (r=0.51-0.83; P<0.05). However, no correlation was detected between the SUV and ReHo in the right caudate and anterior cingulate cortex (r=0.41 and 0.37, respectively; P>0.05). Taken together, these results demonstrated that patients with MDD displayed characteristic patterns regarding changes of brain glucose uptake and ReHo in the resting state. Furthermore, 18F-FDG PET may be a more sensitive technique compared with BOLD-fMRI for the identification of brain lesions in patients with MDD.

Super-Resolution Fluorescence Microscopy for Single Cell Imaging.

In the past two decades, super-resolution fluorescence microscopy has undergone a dynamic evolution. Following proof-of-concept studies with stimulated emission depletion (STED) microscopy, several new approaches such as structured illumination microscopy (SIM), photoactivation localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), have been developed for imaging of nanoscale structural details and fast cellular dynamics in biological research. In this chapter, after briefly explaining their principles, we will describe the recent application of these super-resolution techniques in single cell imaging. In addition, the extension of super-resolution microscopy to 3D, multicolor, live-cell imaging and multimodal imaging are also discussed, significantly improving the precision of single cell imaging. Combining with molecular biology, biochemistry and bio-computing algorithms, super-resolution fluorescence microscopy continues to expand its capabilities and provide comprehensive insights into the details of single cells.

Clinical outcomes and prognostic factors of radioiodine ablation therapy for lymph node metastases from papillary thyroid carcinoma.

OBJECTIVE: A total of 118 patients with papillary thyroid carcinoma treated with radioactive iodine for lymph node metastases were analyzed retrospectively between August 2008 and June 2014. We describe the clinical course of these patients and focus on factors associated with lymph node metastases response to iodine-131 (I) treatment. PATIENTS AND METHODS: A total of 118 postoperative papillary thyroid carcinoma patients who underwent I treatment with lymph nodes as the only site of metastasis on whole-body scan (I Rx-WBS) and single-photon emission computed tomography-computed tomography (SPECT-CT) were enrolled. Clinical and laboratory evaluations including I Rx-WBS, serum thyroglobulin level, and radiographic findings were carried out during follow-up. RESULTS: At the end of follow-up, the rates of complete remission and partial response were 28.0% (33/118) and 52.5% (62/118), respectively. An overall effective rate of 80.5% (95/118) was obtained after three times radioiodine therapy and administration of 3.7-16.7 GBq I. CONCLUSION: Our data indicate that I therapy is highly effective in the treatment of lymph node metastases from papillary thyroid carcinoma; patients with a small size of metastatic lymph node, younger patients, those with lower thyroglobulin levels, and patients with lymph node metastases detectable on the first postablative I Rx-WBS and single-photon emission computed tomography-computed tomography showed a good response to radioiodine ablation therapy.

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response.

The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

Functional assessment of prefrontal lobes in patients with major depression disorder using a dual-mode technique of 3D-arterial spin labeling and 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

The aim of this study was to explore the functions of cerebral blood perfusion and glucose metabolism in the prefrontal lobe of patients with major depression disorder (MDD), and to analyze the correlations between these functional changes and depressive symptoms. 3D-arterial spin labeling (ASL) and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were successfully performed in 17 patients with MDD and 16 healthy controls in a resting state. The depressive symptoms of the patients were classified into seven factors and scored with the Hamilton Depression Rating Scale. Regional cerebral blood flow (CBF) values and standardized uptake values (SUV) of 18F-FDG in the whole brain were respectively compared between the patients and healthy controls using a two-sample t-test, and the correlations between the CBF and SUV in the prefrontal cerebral regions with the patients' Hamilton scores were evaluated using Pearson correlation analysis. Decreased regional CBF was indicated in the bilateral middle and the right superior frontal gyri, and decreased regional SUV was indicated in the bilateral superior, middle and inferior frontal gyri in the MDD patients compared with the controls. Positive correlations were observed between CBF values and aggregate Hamilton scores in the left middle and right middle frontal gyri of the patients. Positive correlations were also observed between SUVs and aggregate Hamilton scores in the left middle and right middle frontal gyri. 18F-FDG PET/CT was indicated to be more sensitive than 3D-ASL in identifying the functional abnormalities in the prefrontal lobe. Decreased CBF and SUV in the prefrontal lobe were closely correlated with Hamilton score. The left middle frontal gyrus may be a key functional region in MDD.

Binary Synergistic Sensitivity Strengthening of Bioinspired Hierarchical Architectures based on Fragmentized Reduced Graphene Oxide Sponge and Silver Nanoparticles for Strain Sensors and Beyond.

Recently, stretchable electronics have been highly desirable in the Internet of Things and electronic skins. Herein, an innovative and cost-efficient strategy is demonstrated to fabricate highly sensitive, stretchable, and conductive strain-sensing platforms inspired by the geometries of a spiders slit organ and a lobsters shell. The electrically conductive composites are fabricated via embedding the 3D percolation networks of fragmentized graphene sponges (FGS) in poly(styrene-block-butadiene-block-styrene) (SBS) matrix, followed by an iterative process of silver precursor absorption and reduction. The slit- and scale-like structures and hybrid conductive blocks of FGS and Ag nanoparticles (NPs) provide the obtained FGS-Ag-NP-embedded composites with superior electrical conductivity of 1521 S cm-1 , high break elongation of 680%, a wide sensing range of up to 120% strain, high sensitivity of ≈107 at a strain of 120%, fast response time of ≈20 ms, as well as excellent reliability and stability of 2000 cycles. This huge stretchability and sensitivity is attributed to the combination of high stretchability of SBS and the binary synergistic effects of designed FGS architectures and Ag NPs. Moreover, the FGS/SBS/Ag composites can be employed as wearable sensors to detect the modes of finger motions successfully, and patterned conductive interconnects for flexible arrays of light-emitting diodes.

SPECT and PET radiopharmaceuticals for molecular imaging of apoptosis: from bench to clinic.

Owing to the central role of apoptosis in many human diseases and the wide-spread application of apoptosis-based therapeutics, molecular imaging of apoptosis in clinical practice is of great interest for clinicians, and holds great promises. Based on the well-defined biochemical changes for apoptosis, a rich assortment of probes and approaches have been developed for molecular imaging of apoptosis with various imaging modalities. Among these imaging techniques, nuclear imaging (including single photon emission computed tomography and positron emission tomography) remains the premier clinical method owing to their high specificity and sensitivity. Therefore, the corresponding radiopharmaceuticals have been a major focus, and some of them like 99mTc-Annexin V, 18F-ML-10, 18F-CP18, and 18F-ICMT-11 are currently under clinical investigations in Phase I/II or Phase II/III clinical trials on a wide scope of diseases. In this review, we summarize these radiopharmaceuticals that have been widely used in clinical trials and elaborate them in terms of radiosynthesis, pharmacokinetics and dosimetry, and their applications in different clinical stages. We also explore the unique features required to qualify a desirable radiopharmaceutical for imaging apoptosis in clinical practice. Particularly, a perspective of the impact of these clinical efforts, namely, apoptosis imaging as predictive and prognostic markers, early-response indicators and surrogate endpoints, is also the highlight of this review.