Development of High-Precision NO2 Gas Sensor Based on Non-Dispersive Infrared Technology.

Increasing concerns about air quality due to fossil fuel combustion, especially nitrogen oxides (NOx) from marine and diesel engines, necessitate advanced monitoring systems due to the significant health and environmental impacts of nitrogen dioxide (NO2). In this study, a gas detection system based on the principle of the non-dispersive infrared (NDIR) technique is proposed. Firstly, the pyroelectric detector was developed by employing an ultra-thin LiTaO3 (LT) layer as the sensitive element, integrated with nanoscale carbon material prepared by wafer-level graphics technology as the infrared absorption layer. Then, the sensor was hermetically sealed using inert gas through energy storage welding technology, exhibiting a high detectivity (D*) value of 4.19 × 108 cm·âˆšHz/W. Subsequently, a NO2 gas sensor was engineered based on the NDIR principle employing a Micro Electro Mechanical System (MEMS) infrared (IR) emitter, featuring a light path chamber length of 1.5 m, along with integrated signal processing and software calibration algorithms. This gas sensor was capable of detecting NO2 concentrations within the range of 0-500 ppm. Initial tests indicated that the gas sensor exhibited a full-scale relative error of less than 0.46%, a limit of 2.8 ppm, a linearity of -1.09%, a repeatability of 0.47% at a concentration of 500 ppm, and a stability of 2% at a concentration of 500 ppm. The developed gas sensor demonstrated significant potential for application in areas such as industrial monitoring and analytical instrumentation.

PSMA-reactive NB7 single domain antibody fragment: A potential scaffold for developing prostate cancer theranostics.

INTRODUCTION: Single domain antibody fragments (sdAbs) are an appealing scaffold for radiopharmaceutical development due to their small size (~15 kDa), high solubility, high stability, and excellent tumor penetration. Previously, we developed NB7 sdAb, which has very high affinity for an epitope on PSMA that is different from those targeted by small molecule PSMA inhibitors. Herein, we evaluated NB7 after radioiodination using [*I]SGMIB (1,3,4-isomer) and iso-[*I]SGMIB (1,3,5-isomer), as well as their 211At-labeled analogues. METHODS: [*I]SGMIB, iso-[*I]SGMIB, [211At]SAGMB, and iso-[211At]SAGMB conjugates of NB7 sdAb were synthesized and their binding affinity, cell uptake and internalization were assessed in PSMA+ PC3 PIP and PSMA- PC3 flu cells. Biodistribution studies were performed in mice bearing PSMA+ PC3 PIP xenografts. First, a single-label experiment evaluated the tissue distribution of a NB7 bearing a His6-tag (NB7H6) and labeled with iso-[125I]SGMIB. Three paired-label experiments then were performed to compare: a) NB7 labeled using [*I]SGMIB and iso-[*I]SGMIB, b) 131I- vs 211At-labeled NB7 conjugates and c) [125I]SGMIB-NB7H6 to the small molecule PSMA inhibitor [131I]YF2. RESULTS: All NB7 radioconjugates bound specifically to PSMA with dissociation constants, Kd, in the low nM range (1.4-6.4 nM). An initial biodistribution study demonstrated good tumor uptake for iso-[125I]SGMIB-NB7H6 (7.2 ± 1.5 % ID/g at 1 h) and no deleterious effect of the His6-tag on renal activity levels, which declined to 3.1 ± 1.1 % ID/g by 4 h. Paired-label biodistribution found no distinction between the two SGMIB isomer NB7 conjugates with the [131I]SGMIB-NB7-to-iso-[125I]SGMIB-NB7 tumor uptake ratios not significantly different from unity: 1.06 ± 0.08 at 1 h, 1.04 ± 0.12 at 4 h, and 1.07 ± 0.09 at 24 h. Both isomer conjugates cleared rapidly from normal tissues and exhibited very low uptake in thyroid, lacrimal and salivary glands. Paired-label biodistribution of [131I]SGMIB-NB7H6 and [211At]SAGMB-NB7H6 demonstrated similar tumor uptake and kidney clearance for the two radioconjugates. However, levels of 211At in thyroid, stomach, salivary and lacrimal glands were significantly higher (P < 0.05) that those for 131I suggesting greater dehalogenation for [211At]SAGMB-NB7H6. Finally, co-administration of [125I]SGMIB-NB7H6 and [131I]YF2 demonstrated good tumor uptake for both with considerably more rapid renal clearance for the NB7 radioconjugate. CONCLUSION: NB7 radioconjugates exhibited good accumulation in PSMA-positive xenografts with rapid clearance from kidney and other normal tissues. We conclude that NB7 is a potentially useful scaffold for developing PSMA-targeted theranostics with different characteristics than current small molecule and antibody-based approaches.

Hepatic artery infusion chemotherapy combined with the FOLFOX regimen for the treatment of hepatocellular carcinoma: recent advances and literature review.

INTRODUCTION: The incidence of primary liver cancer (PLC) has experienced a significant global increase, primarily attributed to the rise in hepatocellular carcinoma (HCC). Unfortunately, HCC is often diagnosed in advanced stages, leaving patients with limited treatment options. Therefore, transformation therapy is a crucial approach for long-term survival and radical resection in patients with advanced HCC. Conversion therapy has demonstrated promise in the treatment of advanced HCC. When integrated with the FOLFOX regimen, hepatic artery infusion chemotherapy (HAIC) can significantly improve tumor response efficiency, leading to high conversion and resection rates. AREAS COVERED: We reviewed landmark trials of HAIC in combination with different drugs or means for the treatment of HCC to determine the clinical value of HAIC-centric translational therapies in HCC treatment. Furthermore, we specifically emphasize the advantages associated with employing FOLFOX-HAIC in the treatment of advanced HCC. EXPERT OPINION: The combination of HAIC with the FOLFOX regimen can help prevent the low intratumoral accumulation and high adverse reaction rate caused by the FOLFOX alone, holding significant potential in the comprehensive treatment of future HCC patients.

Association of possible sarcopenia with major chronic diseases and multimorbidity among middle-aged and older adults: Findings from a national cross-sectional study in China.

AIM: This study investigated the prevalence of possible sarcopenia (PSA) in a large sample of middle-aged and older adults, and determined the association between PSA, major chronic diseases and the number of chronic diseases. METHODS: A total of 14 917 adults aged ≥40 years were included in the analysis. The handgrip strength and the five-time chair stand test were used to assess PSA. The participants' major chronic diseases were divided into 14 categories. Four categories were created based on the participants' number of chronic illnesses: 0, 1, 2 and ≥3. RESULTS: The present study found an overall prevalence of PSA of 23.6% among Chinese middle-aged and older adults aged ≥40 years, with the risk increasing with advancing age. PSA was significantly associated with most categories of chronic diseases and multimorbidity. The closely independent associations were obtained for stroke; emotional, nervous or psychiatric problems; chronic lung disease, asthma, heart disease, hypertension and arthritis or rheumatism. Compared with participants with 0 chronic disease, those with two or more chronic diseases had higher odds for PSA. However, the association between PSA and the number of chronic diseases varied in different sex and age groups. CONCLUSIONS: The findings suggest that PSA is associated with major chronic diseases among middle-aged and older adults. People with two or more chronic diseases have a greater likelihood of PSA compared with those without chronic diseases, and the association between PSA and the number of chronic diseases largely depended on sex and age. Geriatr Gerontol Int 2023; 23: 925-931.

Review immune response of targeting CD39 in cancer.

The ATP-adenosine pathway has emerged as a promising target for cancer therapy, but challenges remain in achieving effective tumor control. Early research focused on blocking the adenosine generating enzyme CD73 and the adenosine receptors A2AR or A2BR in cancer. However, recent studies have shown that targeting CD39, the rate-limiting ecto-enzyme of the ATP-adenosine pathway, can provide more profound anti-tumor efficacy by reducing immune-suppressive adenosine accumulation and increasing pro-inflammatory ATP levels. In addition, combining CD39 blocking antibody with PD-1 immune checkpoint therapy may have synergistic anti-tumor effects and improve patient survival. This review will discuss the immune components that respond to CD39 targeting in the tumor microenvironment. Targeting CD39 in cancer has been shown to not only decrease adenosine levels in the tumor microenvironment (TME), but also increase ATP levels. Additionally, targeting CD39 can limit the function of Treg cells, which are known to express high levels of CD39. With phase I clinical trials of CD39 targeting currently underway, further understanding and rational design of this approach for cancer therapy are expected.

Physical activity intensity, frequency, duration, volume and the risk of possible sarcopenia in middle-aged and older adults.

This study explored the association of physical activity (PA) from different dimensions including intensity, frequency, duration, and volume with possible sarcopenia (PSA), and established the PA cut-off value to identify PSA in middle-aged and older adults. The data in this study were from the China Health and Retirement Longitudinal Study in 2015. There were 7,957 adults aged over 45 years in the analysis. PA was assessed using a modified version of the International Physical Activity Questionnaire Short Form. Muscle strength and physical performance were measured to define PSA. Results showed that men spending at least 3 days each week, more than 10 min each time on vigorous-intensity PA, or a minimum of 933 Mets on total PA each week had a lower risk of PSA. In women, spending at least 3 days each week, more than 30 min each time on moderate-intensity PA, or taking at least 6 days each week, more than 120 min each time on low-intensity PA, or a minimum of 933 Mets on total PA each week was associated with a lower risk of PSA. In older adults (≥ 65 years), spending at least one day each week, more than 30 min each time on vigorous-intensity PA, or taking a minimum of 933 Mets on total PA each week was linked with a decreased risk of PSA. However, no significant associations were found between any PA dimensions and PSA in middle-aged adults (45-64 years). A receiver operating characteristic analysis showed that the PA cut-off value was 695 and 693 Mets each week for predicting PSA for men and women. The findings suggested that the intensity, frequency, duration, and weekly volume of PA is associated with the risk of PSA in middle-aged and older adults, and the association largely depends on sex and age. The PA cut-off value may be an early indication for a higher risk of sarcopenia.

Effective Treatment of Human Breast Carcinoma Xenografts with Single-Dose 211At-Labeled Anti-HER2 Single-Domain Antibody Fragment.

Single-domain antibody fragments (sdAbs) are attractive for targeted α-particle therapy, particularly with 211At, because of their rapid accumulation in tumor and clearance from normal tissues. Here, we evaluate the therapeutic potential of this strategy with 5F7 and VHH_1028-2 sdAbs that bind with high affinity to domain IV of human epidermal growth factor receptor type 2 (HER2). Methods: The HER2-specific sdAbs and HER2-irrelevant VHH_2001 were labeled using N-succinimidyl-3-211At-astato-5-guanidinomethyl benzoate (iso-211At-SAGMB). The cytotoxicity of iso- 211At-SAGMB-5F7 and iso- 211At-SAGMB-VHH_2001 were compared on HER2-expressing BT474 breast carcinoma cells. Three experiments in mice with subcutaneous BT474 xenografts were performed to evaluate the therapeutic effectiveness of single doses of iso- 211At-SAGMB-5F7 (0.7-3.0 MBq), iso- 211At-SAGMB-VHH_1028 (1.0-3.0 MBq), and iso- 211At-SAGMB-VHH_1028 and iso- 211At-SAGMB-VHH_2001 (∼1.0 MBq). Results: Clonogenic survival of BT474 cells was reduced after exposure to iso- 211At-SAGMB-5F7 (D0 = 1.313 kBq/mL) whereas iso- 211At-SAGMB-VHH_2001 was ineffective. Dose-dependent tumor growth inhibition was observed with 211At-labeled HER2-specific 5F7 and VHH_1028 but not with HER2-irrelevant VHH_2001. At the 3.0-MBq dose, complete tumor regression was seen in 3 of 4 mice treated with iso- 211At-SAGMB-5F7 and 8 of 11 mice treated with iso- 211At-SAGMB-VHH_1028; prolongation in median survival was 495% and 414%, respectively. Conclusion: Combining rapidly internalizing, high-affinity HER2-targeted sdAbs with the iso- 211At-SAGMB residualizing prosthetic agent is a promising strategy for targeted α-particle therapy of HER2-expressing cancers.

CD155 in tumor progression and targeted therapy.

CD155, also known as the poliovirus receptor (PVR), has received considerable attention in recent years because of its intrinsic and extrinsic roles in tumor progression. Although barely expressed in host cells, CD155 is upregulated in tumor-infiltrating myeloid cells. High expression of CD155 in tumor cells across multiple cancer types is common and associated with poor patient outcomes. The intrinsic functions of CD155 in tumor cells promote tumor progression and metastasis, whereas its extrinsic immunoregulatory functions in the tumor microenvironment (TME) involve interaction with the upregulated inhibitory immune cell receptor and checkpoint TIGIT, suggesting that CD155 and CD155 pathways are promising tumor immunotherapy targets. Preclinical studies demonstrate that targeting CD155 and its receptor (anti-TIGIT) using a single treatment or in combination with anti-PD-1 can improve immune-mediated tumor control. However, there is still a limited understanding of CD155 and its associated targeting strategies, especially antibody and immune cell editing-related strategies of CD155 in cancer. Here, we review the role of CD155 in host and tumor cells in controlling tumor progression and discuss the potential of targeting CD155 for tumor therapy.

ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway.

AIM: In digestive system, colorectal cancer (CRC) is a common malignant tumor. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in CRC, and the aberrant activation of this pathway is associated with tumorigenesis. We aimed to explore the role of Rho GTPase activating protein 9 (ARHGAP9) in the progression of CRC as well as its regulatory effects on the PI3K/AKT/mTOR pathway. METHODS: The expression of ARHGAP9 in CRC tumor tissues and cell lines were detected using reverse transcription-quantitative PCR (qRT-PCR). 5-ethynyl-2'-deoxyuridine (EdU) assay was applied to test the cell proliferation. Cell migration and invasion were both assessed through transwell assay. Xenograft mouse models were constructed to explore the effects of ARHGAP9 on CRC in vivo. The expressions of PI3K/AKT/mTOR-activating factors and epithelial-mesenchymal transition (EMT)-related factors were all determined using western blot. LY294002 was employed to block PI3K/AKT/mTOR pathway in CRC cells. RESULTS: The expression of ARHGAP9 was down-regulated in CRC tumor tissues and cell lines when compared to normal tissues and cells. The over-expression of ARHGAP9 inhibited cell proliferation, invasion, migration and EMT in CRC cell lines while the knockdown of ARHGAP9 promoted them. In addition, ARHGAP9 up-regulation inhibited the activation of PI3K/AKT/mTOR signaling pathway in CRC cell lines while ARHGAP9 down-regulation led to an opposite effect. The over-expression of ARHGAP9 suppressed CRC tumor growth in vivo. When the PI3K/AKT/mTOR pathway was blocked in CRC cells, the effects of ARHGAP9 knockdown on cell proliferation, migration, invasion and EMT were all overturned. CONCLUSION: ARHGAP9 inhibited the malignant phenotypes of CRC cells via interdicting PI3K/AKT/mTOR signaling pathway.

Evaluation of an 131I-labeled HER2-specific single domain antibody fragment for the radiopharmaceutical therapy of HER2-expressing cancers.

Radiopharmaceutical therapy (RPT) is an attractive strategy for treatment of disseminated cancers including those overexpressing the HER2 receptor including breast, ovarian and gastroesophageal carcinomas. Single-domain antibody fragments (sdAbs) exemplified by the HER2-targeted VHH_1028 evaluated herein are attractive for RPT because they rapidly accumulate in tumor and clear faster from normal tissues than intact antibodies. In this study, VHH_1028 was labeled using the residualizing prosthetic agent N-succinimidyl 3-guanidinomethyl 5-[131I]iodobenzoate (iso-[131I]SGMIB) and its tissue distribution evaluated in the HER2-expressing SKOV-3 ovarian and BT474 breast carcinoma xenograft models. In head-to-head comparisons to [131I]SGMIB-2Rs15d, a HER2-targeted radiopharmaceutical currently under clinical investigation, iso-[131I]SGMIB-VHH_1028 exhibited significantly higher tumor uptake and significantly lower kidney accumulation. The results demonstrated 2.9 and 6.3 times more favorable tumor-to-kidney radiation dose ratios in the SKOV-3 and BT474 xenograft models, respectively. Iso-[131I]SGMIB-VHH_1028 was prepared using a solid-phase extraction method for purification of the prosthetic agent intermediate Boc2-iso-[131I]SGMIB that reproducibly scaled to therapeutic-level doses and obviated the need for its HPLC purification. Single-dose (SKOV-3) and multiple-dose (BT474) treatment regimens demonstrated that iso-[131I]SGMIB-VHH_1028 was well tolerated and provided significant tumor growth delay and survival prolongation. This study suggests that iso-[131I]SGMIB-VHH_1028 is a promising candidate for RPT of HER2-expressing cancers and further development is warranted.

Do Arch Height and Arch Stiffness Relate to Physical Performance in Adult Men?

Foot arch plays an important role in bearing body weight, absorbing ground reaction forces and maintaining balance, and its structure and function are bound to have a profound effect on physical activities and sports. Arch height and arch stiffness are 2 factors that represent the structure and function of the arch. Therefore, the purpose of this study was to explore the associations of arch height and arch stiffness with physical performance. A total of 56 men (aged 49.00 ± 7.95 years, mean body mass index [BMI] 26.80 ± 3.75 kg/m2) participated in this study. A 3-dimensional laser scanner was employed to obtain foot structure information of each participant, from which the arch height index (AHI) and arch stiffness index (ASI) were computed. Physical performance measures including agility, power, and proprioception were tested in a random order. The results indicated that the stepping forward and backward and vertical jump that represent agility and force respectively were negatively and significantly associated with AHI (r = -0.27, p = .045; r = -0.35, p = .009). When adjusted for age and BMI, only height of vertical jump was found to be correlated significantly with AHI (r = -0.29, p = .040); while no significant relationships were observed between physical performance measures and ASI. Multivariate linear regression analysis showed that AHI, age, and BMI can effectively predict the height of vertical jump. This study demonstrates that there is a negative correlation between arch height and muscle power of lower limbs in adult men.

Effect of smoking status on spirometric lung age in adult Chinese Men.

Smoking is one of the most unhealthy behaviours and responsible for a variety of respiratory diseases. Although spirometric lung age (SLA) is regarded as an effective way to augment the smoking quit rate in other countries, it has not been calculated in Chinese smokers. Thus, the aim of this study was to determine the association of SLA with smoking status, and further explore whether smoking duration, dependence and other factors such as obesity and physical exercise affect SLA in Chinese current smokers. A total of 431 healthy men aged 20 years and older took part in the study from September 2018 to August 2019. Spirometric test was measured through a portable spirometry, and smoking status including smoking duration and dependence was investigated by using a questionnaire. SLA was calculated from an established equation which is based on the inverse calculation of the forced expiratory volume in one second in the Chinese population. Lung age difference (∆LA) could be obtained by counting the difference between SLA and chronological age. Results indicated that ∆LA is remarkably higher in current smokers than that in ex-smokers and non-smokers (p < 0.01). The study also revealed that smoking duration and dependence are related to ∆LA. Smokers with long smoking duration (smoked ≥10 years) and high dependence (consumed ≥20 cigarettes per day) had a significantly higher ∆LA than their counterparties (p < 0.01). Multiple regression analysis showed that body mass index, smoking duration and cigarettes per day were independently correlated with ∆LA in the current smokers (p < 0.01). The findings suggest that not only smoking or not, but smoking duration, dependence and obesity are strongly associated with SLA.

Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy.

AIM: To develop an innovative 211At nanoplatform with high radiolabeling efficiency and low in vivo deastatination for future targeted alpha-particle therapy (TAT) to treat cancer. METHODS: Star-shaped gold nanoparticles, gold nanostars (GNS), were used as the platform for 211At radiolabeling. Radiolabeling efficiency under different reaction conditions was tested. Uptake in the thyroid and stomach after systemic administration was used to evaluate the in vivo stability of 211At-labeled GNS. A subcutaneous U87MG human glioma xenograft murine model was used to preliminarily evaluate the therapeutic efficacy of 211At-labeled GNS after intratumoral administration. RESULTS: The efficiency of labeling GNS with 211At was almost 100% using a simple and rapid synthesis process that was completed in only 1 min. In vitro stability test in serum showed that more than 99% of the 211At activity remained on the GNS after 24 h incubation at 37°C. In vivo biodistribution results showed low uptake in the thyroid (0.44-0.64%ID) and stomach (0.21-0.49%ID) between 0.5 and 21 h after intravenous injection, thus indicating excellent in vivo stability of 211At-labeled GNS. The preliminary therapeutic efficacy study demonstrated that 211At labeled GNS substantially reduced tumor growth (P < 0.001; two-way ANOVA) after intratumoral administration. CONCLUSION: The new 211At radiolabeling strategy based on GNS has the advantages of a simple process, high labeling efficiency, and minimal in vivo dissociation, making it an attractive potential platform for developing TAT agents that warrants further evaluation in future preclinical studies directed to evaluating prospects for clinical translation.

MICAL1 (molecule interacting with CasL 1) protects oligodendrocyte cells from oxidative injury through regulating apoptosis, autophagy in spinal cord injury.

Molecule's mechanism of action interacting with CasL 1 (MICAL1) in spinal cord injury (SCI) is unclear. This study aimed to detect the function of MICAL1 in SCI. Western blot was used to analyze the change of MICAL1 in vivo. Immunofluorescence staining was used to detect the location of MICAL1 expression. Oligodendrocyte cells were treated with H2O2 to induce oxidative injury. Subsequently, siRNA transfection was performed to decrease MICAL1 expression in oligodendrocyte cells. Then, the effects of MICAL1 on oxidative stress, apoptosis, and autophagy were assessed. We found that silencing of MICAL1 could significantly reduce the levels of the nuclear factor erythroid 2-related factor 2 (Nrf2), increase the expression of pro-apoptotic factors (Bax and C-caspase 3), decrease the levels of anti-apoptotic factor (Bcl-2) and pro-autophagy factors (Beclin1 and LC3B). Therefore, MICAL1 is a potential target gene for SCI clinical therapy.

CircSMYD4 regulates proliferation, migration and apoptosis of hepatocellular carcinoma cells by sponging miR-584-5p.

BACKGROUND: There is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism. METHODS: The expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay and Spearman correlation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells. RESULTS: CircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC. CONCLUSION: CircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p.

The Influence of Gender, Age, and Body Mass Index on Arch Height and Arch Stiffness.

Arch structure and arch function play an important role in maintaining balance, bearing body weight, and absorbing ground reaction forces. However, arch structure and arch function are known to vary extensively and may be affected by factors such as gender, age, and obesity. Therefore, the purpose of this study was to examine the influence of gender, age, and body mass index (BMI) on arch height and arch stiffness. A total of 173 participants (aged 57.60 ± 11.19 years, mean BMI 25.12 ± 3.93 kg/m2) participated in this cross-sectional study. A 3-dimensional laser scanner was used to measure foot structure information in each subject, from which arch height and arch stiffness were calculated. The results showed that women had low-arched feet compared with men (p = .001), and no arch stiffness difference was found. Older individuals tended to have a stiffer arch than middle-aged and younger individuals (p < .05), and no arch height difference was found. BMI had an impact on arch height (p < .05) but not arch stiffness. Finally, a weak positive relationship existed between arch height and arch stiffness (r = 0.32, p < .01). The findings suggest that gender, age, and obesity have a certain impact on arch structure and arch stiffness. Figuring out the relationship between these factors and arch structure may be helpful in understanding the bases of foot deformity and foot dysfunction.

Labeling Monoclonal Antibody with α-emitting 211At at High Activity Levels via a Tin Precursor.

Background: In a previous clinical study, the authors evaluated the potential of antitenascin C monoclonal antibody (mAb) 81C6 labeled with 211At via the prosthetic agent N-succinimidyl 3-[211At]astatobenzoate (SAB) for the treatment of primary brain tumors. Although encouraging results were obtained, labeling chemistry failed while attempting to escalate the dose to 370 MBq. The goal of the current study was to develop a revised procedure less susceptible to radiolysis-mediated effects on 211At labeling that would be suitable for use at higher activity levels of this α-emitter. Materials and Methods: Addition of N-chlorosuccinimide to the methanol used to remove the 211At from the cryotrap after bismuth target distillation was done to thwart radiolytic decomposition of reactive 211At and the tin precursor. A series of 11 reactions were performed to produce SAB at initial 211At activity levels of 0.31-2.74 GBq from 50 µg of N-succinimidyl 3-trimethylstannylbenzoate (Me-STB), which was then reacted with murine 81C6 mAb without purification of the SAB intermediate. Radiochemical purity, immunoreactive fraction, sterility, and apyrogenicity of the 211At-labeled 81C6 preparations were evaluated. Results: Murine 81C6 mAb was successfully labeled with 211At using these revised procedures with improved radiochemical yields and decreased overall synthesis time compared with the original clinical labeling procedure. Conclusions: With 2.74 GBq of 211At, it was possible to produce 1.0 GBq of 211At-labeled 81C6 with an immunoreactive fraction of 92%. These revised procedures permit production of 211At-labeled mAbs suitable for use at clinically relevant activity levels.