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Gastrin-releasing peptide (GRP) receptors are over-expressed in various human tumor including breast and prostate which can be targeted with bombesin for diagnosis and targeted therapy. High abdominal accumulation and the poor in vivo stability of radiolabeled bombesin analogues may represent a limitation for diagnostic imaging and targeted therapy. In this study a new bombesin derivative was labeled with Tc via HYNIC and tricine as a coligand and investigated further. The peptide HYNIC conjugate was synthesized on a solid phase using Fmoc strategy. Labeling with Tc was performed at 100 °C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of human serum at 37 °C up to 24 h. Internalization was studied with the human GRP receptor cell line PC-3. The Biodistribution was studied in mice. Labeling yield of >98 % was obtained to correspond a specific activity of ~80.9 GBq/μmol. Radioconjugate internalization into PC-3 cells was high and specific (15.6 ± 1.9 % at 4 h). A high and specific uptake in GRP-receptor-positive organs such as mouse tumor and pancreas (2.11 ± 0.18 and 1.78 ± 0.09 % ID/g after 1 h respectively) was also determined. [ABSTRACT FROM AUTHOR]

A variety of human tumors like prostate and breast cancer express bombesin receptors. Due to this a new bombesin analogue was labeled with 99mTc via HYNIC and tricine as a coligand and investigated further. Peptide was synthesized on a solid phase using Fmoc strategy. Labeling with 99mTc was performed at 100 °C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of human serum at 37 °C up to 24 h. Internalization was studied with the human GRP receptor cell line PC-3. The biodistribution was studied in mice. Labeling yield of >98% was obtained corresponding to a specific activity of ~80.9 GBq/μmol. Radiopeptide internalization into PC-3 cells was moderate and specific (10.7 ± 1.2% at 4 h). A high and specific GRP receptor expressing mouse tumor and pancreas uptake (1.12 ± 0.08 and 1.04 ± 0.11% ID/g after 1 h respectively) was also determined. [ABSTRACT FROM AUTHOR]

Background and Objective: Non-suicidal self-injury (NSSI) is a psychological disorder that the sufferer consciously damages their body tissues, often too severe that requires intensive care medicine. As some individuals hide their NSSI behaviors, other people can only identify them if they catch them while injuring, or via dedicated questionnaires. However, questionnaires are long and tedious to answer, thus the answers might be inconsistent. Hence, in this study for the first time, we abstracted a larger questionnaire (of 662 items in total) to own only 22 items (questions) via data mining techniques. Then, we trained several machine learning algorithms to classify individuals based on their answers into two classes., Methods: Data from 277 previously-questioned participants is used in several data mining methods to select features (questions) that highly represent NSSI, then 245 different people were asked to participate in an online test to validate those features via machine learning methods., Results: The highest accuracy and F1 score of the selected features-via the Genetics algorithm-are 80.0% and 74.8% respectively for a Random Forest algorithm. Cronbach's alpha of the online test (validation on the selected features) is 0.82. Moreover, results suggest that an MLP can classify participants into two classes of NSSI Positive and NSSI Negative with 83.6% accuracy and 83.7% F1-score based on the answers to only 22 questions., Conclusion: While previously psychologists used many combined questionnaires to see whether someone is involved in NSSI, via various data mining methods, the present study showed that only 22 questions are enough to predict if someone is involved or not. Then different machine learning algorithms were utilized to classify participants based on their NSSI behaviors, among which, an MLP with 10 hidden layers had the best performance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Farajzadeh, Sadeghzadeh. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Among the musculoskeletal disorders in the world, osteoarthritis is the most common, affecting most of the body joints, especially the knee. Clinical radiographic imaging methods are commonly used to diagnose osteoarthritis thanks to their cheapness and availability. Due to the low quality and indiscernibility of these images, however, accurate osteoarthritis diagnosis has always faced inaccuracies, such as the wrong diagnosis. One of the osteoarthritis hallmarks is joint space narrowing. Thus, its degree and severity can be determined relatively by assessing the space between the bones in the joint. Therefore, in this research, a deep residual neural network, termed IJES-OA Net, is presented to automatically grade (classify) the severity of knee osteoarthritis via radiographs. This is achieved by tuning it in a way to have it focused on the distance of the edges of the bones inside the knee joint. Experimental results which are conducted on MOST (for training) and OAI (for validation and testing) datasets show that the IJES-OA Net achieves high average accuracy as well as average precision (80.23% and 0.802, respectively) while having less complexity compared to other methods. Additionally, the resulting attention maps from IJES-OA Net are accurate enough that increase experts' reliance on the provided results., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 IPEM. Published by Elsevier Ltd. All rights reserved.)

Purpose: In this study, we designed a new linear 6-Hydrazinonicotinamide (HYNIC)-conjugated peptide (HYNIC-KRWrNM) (M-6) and labeled with technetium-99m for gamma imaging of glioblastoma as a α v β 3 -positive tumor. We evaluated tumor targeting ability of this radio-peptide and compared with previous 99m Tc-labeled HYNIC-conjugated RGD analogue peptides., Procedures: One new linear peptide (HYNIC-KRWrNM) (M-6) was designed and labeled with technetium-99m in the presence of 2-[[1,3-dihydroxy-2-(hydroxymethyl) propan-2-yl] amino] acetic acid (Tricine)/Ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligand system. Then, this 99m Tc-labeled peptide ([ 99m Tc]Tc-M-7) was evaluated for in vitro stability in saline and serum, specific binding assay, internalization, and binding affinity (K d ). In addition, we performed biodistribution study and planar imaging on nude mice bearing U87-MG xenograft as a α v β 3 -positive tumor., Results: The radiochemical yield of [ 99m Tc]Tc-M-7 was obtained ˃95%. This 99m Tc-labeled peptide remained stable and intact in saline solution after 24 h incubation. In addition, metabolic stability of this 99m Tc-labeled peptide was obtained ˃60% after 4 h incubation in serum. The K d value for [ 99m Tc]Tc-M-7 was obtained 5.2 ± 1.0 nM. Based on biodistribution results in nude mice bearing U87-MG xenograft, tumor/muscle activity ratio was 6.22 and decreased to 1.89 in blocking group at the same time point (4 h p.i.). The blocking experiment results also indicated that tumor uptake and kidney uptake were α v β 3 -mediated. In comparison with previous HYNIC-conjugated RGD analogue peptides, kidneys had the highest uptake of this 99m Tc-labeled peptide (52.29 ± 11.48 at 1.5 h p.i. and 27.04 ± 0.66%ID/g at 4 h p.i.). Finally, similar to previous 99m Tc-labeled HYNIC-conjugated RGD analogue peptides, [ 99m Tc]Tc-M-7 showed acceptable tumor uptake after 4 h post-injection (based on ROI technique, target-to-background activity ratio = 3.80)., Conclusions: This small linear 99m Tc-labeled peptide, with high affinity to α v β 3 integrin, desirable water solubility, and cost efficient, demonstrates a potent tumor targeting ability as well as previous HYNIC-conjugated RGD analogue peptides. Hence, [ 99m Tc]Tc-M-7 can be of service to as a new candidate for early detection of α v β 3 -positive tumors., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background & Objective: Continuity of midwifery-led care during labour and birth is considered optimal. To ensure its sustainability in practice where limited evidence is available, the aim of the present study was to explore midwives' lived experiences of delivering continuous midwife-led intrapartum care., Methods: This study took a qualitative approach in meeting its aim. Participants were midwives working in the labour wards of private and public hospitals in Iran. The data were purposefully collected in 2019 through in-depth, semi-structured, and face-to-face interviews with midwives (n = 10) aged between 26 and 55 years. A thematic analysis based on descriptive phenomenology was undertaken to make sense of the data collected., Results: "Wanting to lead continuous woman-centered care but being unable to" was identified as an overarching theme. Three other themes "emphasis on the non-interventional care", "midwifery-specific focus" and "barriers and challenges of midwifery care" were also identified. Ultimately, midwives described knowing how to and wanting to lead continuous 'woman'-centered care but being unable to. Perceived barriers included lack of familiarity with and knowledge in relation to childbirth, the insignificant role of midwives in decision making, obstetrician utilitarianism, high workloads along with work-related stress argument-driven communication between midwives and obstetricians and an absence of a 'triangle of trust' in care., Conclusion: Future research strategies could usefully include obstetricians and focus on the upscaling of midwifery in Iran using continuity of care models, highlight the value of midwives, identify why uptake of antenatal education in Iran is poor and develop user friendly, evidence based, midwife-led programs. Initiatives aiming to promote mutual professional respect, trust and collegiality and increased remuneration for midwifery work would be also welcomed in pursuit of reducing maternal and infant mortality in Iran., (© 2022. The Author(s).)

Cancer detection in its early stages may allow patients to receive the proper treatment and save lives along with recovering the routine lifestyles. Breast cancer is of the top leading causes of mortality among women all around the globe. A source to find these cancerous nuclei is through analyzing histopathology images. These images, however, are very complex and large. Thus, locating the cancerous nuclei in them is very challenging. Hence, if an expert fails to diagnose their patients via these images, the situation may be exacerbated. Therefore, this study aims to introduce a method to mask as many cancer nuclei on histopathology images as possible with a high visual aesthetic to make them distinguishable by experts easily. A tailored residual fully convolutional encoder-decoder neural network based on end-to-end learning is proposed to issue the matter. The proposed method is evaluated quantitatively and qualitatively on ER + BCa H&E-stained dataset. The average detection accuracy achieved by the method is 98.61%, which is much better than that of competitors., (Copyright © 2022. Published by Elsevier Ltd.)

Response surface methodology (RSM) based on the D-optimal algorithm was employed here for the electrospinning of nanoclay/polyacrylonitrile (PAN) composite scaffold by the aim of obtaining the lower fiber diameter and better mechanical properties for bone regeneration. The input parameters included the electrospinning voltage, flow rate and the ratio of nanoclay/PAN and the obtained values for the optimum point were 17 kV for the applied voltage, 0.41 ml/hr for flow rate, and 19.06% for the nanoclay/PAN ratio. The composite scaffold was fabricated in accordance with these optimum values and then studied by scanning electron microscopy and tensile apparatus. The fiber diameter and Young's modulus of the prepared scaffold were respectively 145 ± 12 nm and 267 ± 8.7 MPa that the values were between predicted by RSM. Moreover, the biocompatibility and osteogenic differentiation of the composite scaffold were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and alkaline phosphatase assays. The bare scaffold and tissue culture polystyrene were used as control groups. The results approved stronger bioactivity and bone regeneration with the composite scaffold as a presence of clay nanoparticles., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Specific tumor uptake of peptide radiopharmaceuticals depends on tumor binding affinity and their radiochemical purity. Several important parameters that influence the 99m Tc-labeling and consequently the radiochemical purity of 6-hydrazinonicotinamide (HYNIC)-conjugated peptide are radionuclide activity, the amount of peptide, the amount of coligands, and the amount of reducing agents (stannous ion). In this review article, we have attempted studying these parameters in the HYNIC-conjugated peptides (somatostatin, cholecystokinin/gastrin, bombesin, and RGD analogs) from a new perspective to obtain most used and optimized radio-stoichiometric relationships. One of the most important results in this review is that for 99m Tc-labeling of HYNIC-conjugated peptides, it is better to consider the most calculated mole ratio between technetium-99m and the peptide (mole ratio of technetium-99m to the peptide 1:200-400). The statistical results also show that among these 99m Tc-labeled peptides, the most used and favorable coligand is tricine/EDDA with two to one (2:1) mole ratio. These optimized radio-stoichiometric relationships, favorable coligand mole ratio, and applicable radiolabeling points can greatly improve the labeling process of the HYNIC-conjugated peptides, by reducing trial and error, increasing specific activity, and saving materials., (© 2020 John Wiley & Sons, Ltd.)

The aim of this study was to prepare radiolabeled peptide-based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium-99m, two analogs were designed and compared: an antitumor-antibody-derived peptide based on the EPPT sequence and a novel retro-inverso peptidomimetic derivative D (TPPE) structurally modified by replacing the L-amino acids with D-amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC-conjugated peptides were labeled with 99m Tc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99m Tc-HYNIC-EPPT and 99m Tc-HYNIC- D (TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99m Tc-HYNIC- D (TPPE) was more favorable than that of 99m Tc-HYNIC-EPPT as a result of better tumor-to-non-target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99m Tc-HYNIC- D (TPPE) in comparison with 99m Tc-HYNIC-EPPT. The results showed the retro-inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT-29 tumors than the parent peptide., (© 2020 John Wiley & Sons A/S.)

The interactions between arbuscular mycorrhizal fungi (AMF) and non-host species are poorly studied. Particularly scarce is information on members of the Amaranthaceae/Chenopodiaceae family. Sugar beet (Beta vulgaris) plants were co-cultivated with a host species (Hordeum vulgare) in the presence (+AMF) or absence of Rhizophagus intraradices to explore the hypothesis that the presence of an active, pre-established AMF mycelium induces defense responses in the non-host species. Biomass of sugar beet did not respond to the +AMF treatment, while its root exudation of organic acids and phenolic acids was drastically decreased upon co-cultivation with +AMF barley. The most conspicuous effect was observed on a wide range of potential defense parameters being differentially influenced by the +AMF treatment in this non-host species. Antioxidant defense enzymes were activated and the level of endogenous jasmonic acid was elevated accompanied by nitric oxide accumulation and lignin deposition in the roots after long-term +AMF treatment. In contrast, significant reductions in the levels of endogenous salicylic acid and tissue concentration and exudation of phenolic acids indicated that AM fungus hyphae in the substrate did not induce a hypersensitive-type response in the sugar beet roots and downregulated certain chemical defenses. Our results imply that the fitness of this non-host species is not reduced when grown in the presence of an AMF mycelium because of balanced defense costs. Further studies should address the question of whether or not such modulation of defense pattern influences the pest resistance of sugar beet plants under field conditions.

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC-conjugated GnRH analogue and labeled it by 99m Tc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys 6 ]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN-CaP and DU-145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN-CaP were superior to DU-145 cells. The K d values for LN-CaP and DU-145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99m Tc-HYNIC-Ahx-[DLys 6 ]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN-CaP tumor-xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor-mediated. The lesion was visualized clearly using 99m Tc-[DLys 6 ]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys 6 ]GnRH peptide as a promising agent for GnRHR-expressing tumor imaging., (© 2020 John Wiley & Sons A/S.)

Objective: The APT EDB is an aptide specific to the extra domain B (EDB) of fibronectin with high affinity for EDB, which is expressed in malignant tumors including brain cancer (U87MG) and colorectal cancer (HT-29). Aim of this study was to evaluate the [ 99m Tc] Tc-APT EDB potential as an imaging probe for colorectal cancer., Methods: Radiochemical purity was evaluated by HPLC and radio-isotope TLC scanner. Blocking study for specific binding assay and affinity calculation (K d ) on HT-29 cell lines were also carried out. Planar imaging and bio-distribution studies were performed in HT-29 tumor-bearing mice., Results: The APT EDB was efficiently labeled with technetium-99m in high radiochemical yield (up to 97%). Cellular binding study demonstrated specific binding of the [ 99m Tc] Tc-APT EDB in cultured HT-29 cells. The K d value was found to be 40.46 ± 13.39 nM. The tumor-to-muscle ratio was ~ 1.5 in ex vivo bio-distribution study at 1 h after injection. Planar imaging study showed higher activity accumulation in EDB expressing HT-29 tumor relative to muscle (used as control) (~ 1.7) at 1 h., Conclusions: Although more studies are required to find out the full potential of this radio-ligand as an imaging probe, the present results nevertheless provide useful information about [ 99m Tc] Tc-APT EDB , which might be beneficial in design and development of new [ 99m Tc] Tc-APT EDB for efficient targeting of tumor in vivo.

Molecular imaging techniques are increasingly being used in localization, staging and therapy control of cancer. Due to their unique target specificity for the endogenous receptors, radiopeptides have been used widely for the development of radiopharmaceuticals for targeted tumor imaging in nuclear oncology. It is necessary to modify radiolabeled peptides in order to achieve more effective agents. Structural modifications of amino acid chains have significant effect on the metabolic stability, biological activity and efficiency of peptide conjugates that are currently applied as imaging tracers. There are several ways to modify the peptide chain but the most common strategies include amino acid substitutions, cyclization and multimerization. In this review, we have focused on studies involving these kind of modifications on amino acid sequences of radiolabeled peptides and we have provided an overview of the effects of these chemical modifications on the in vitro and in vivo properties of these radioconjugates and their potential as SPECT (Single photon emission computed tomography) and PET (positron emission tomography) imaging agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Arginine-glycine-aspartic acid (RGD) peptide with its specific binding affinity to integrin αvβ3, is widely investigated for the development of molecular imaging probes for diagnosis of αvβ3-positive tumors. The aim of this work was to evaluate the ability of Tc- HYNIC-D(RGD), a novel retro-inverso peptidomimetic derivative for U87MG tumor (αvβ3-positive) imaging., Methods: HYNIC-D(RGD) labeled with Tc using tricine/EDDA as an exchange coligands. Single-photon emission computed tomography imaging and biodistribution study were performed in nude mice bearing U87MG xenograft tumor., Results: The labeling yield was >95%. The radiopeptide showed high uptake value in the U87MG tumor relative to muscle after 2 hours (1.43 ± 0.05 vs. 0.22 ± 0.11 %ID/g). The tumor/muscle ratio was 6.5. Blocking experiment showed specific binding towards tumor. Single-photon emission computed tomography imaging study revealed that radiopeptide had prominent uptake in U87MG tumor., Conclusion: The novel Tc HYNIC- D(RGD) was demonstrated to be a useful radiotracer for the assessment of αvβ3-positive tumor in animal model. Therefore, further clinical and preclinical studies are required.

Background: Cancer is the leading cause of death worldwide. Early detection can reduce the disadvantageous effects of diseases and the mortality in cancer. Nuclear medicine is a powerful tool that has the ability to diagnose malignancy without harming normal tissues. In recent years, radiolabeled peptides have been investigated as potent agents for cancer detection. Therefore, it is necessary to modify radiopeptides in order to achieve more effective agents., Objective: This review describes modifications in the structure of radioconjugates with spacers who have improved the specificity and sensitivity of the peptides that are used in oncologic diagnosis and therapy., Methods: To improve the biological activity, researchers have conjugated these peptide analogs to different spacers and bifunctional chelators. Many spacers of different kinds, such as hydrocarbon chain, amino acid sequence, and poly (ethyleneglycol) were introduced in order to modify the pharmacokinetic properties of these biomolecules., Results: Different spacers have been applied to develop radiolabeled peptides as potential tracers in nuclear medicine. Spacers with different charge and hydrophilicity affect the characteristics of peptide conjugate. For example, the complex with uncharged and hydrophobic spacers leads to increased liver uptake, while the composition with positively charged spacers results in high kidney retention. Therefore, the pharmacokinetics of radio complexes correlates to the structure and total charge of the conjugates., Conclusion: Radio imaging technology has been successfully applied to detect a tumor in the earliest stage. For this purpose, the assessment of useful agents to diagnose the lesion is necessary. Developing peptide radiopharmaceuticals using spacers can improve in vitro and in vivo behavior of radiotracers leading to better noninvasive detection and monitoring of tumor growth., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this study was to develop 99mTc-[HYNIC-X-D-Phe13]-BBN(7-14)NH2 derivatives using two different tripeptidic spacer groups (X=GGG and X=SSS) in order to improve its pharmacokinetics, in vitro stability, specific binding, and affinity., Background: Bombesin (BBN), a 14-aminoacid amphibian peptide homolog of mammalian gastrinreleasing peptide (GRP), has demonstrated the ability to bind with high affinity and specificity to GRP receptor, which is overexpressed on a variety of human cancers., Methods: Peptide conjugates labeled with 99mTc using tricine-EDDA and radiochemical purity was assessed by TLC and HPLC. The stability of radio conjugates was evaluated in the presence of saline and human serum. Affinity, internalization, and also dissociation Constant was evaluated using MDAMB- 231 and PC-3 cell line. Biodistribution study was performed in BALB/C mice., Results: Labeling yield of ˃95% was obtained. The change introduced in the BBN sequence increased plasma stability. In vitro blocking studies showed that binding and internalization of both radiolabeled peptides are mediated by their receptors on the surface of MDA-MB-231 and PC-3 cells. Biodistribution results demonstrated a rapid blood clearance, with predominantly renal excretion. Specific binding in GRP receptor-positive tissues, such as pancreas was confirmed with a blocking study., Conclusion: The introduction of the spacer sequence between chelator and BBN(7-14) led to improved bidistribution. Analog with tri-Gly spacer is the more promising radiopeptide for targeting GRP receptors than Ser conjugates. Therefore, these analogs can be considered as a candidate for the identification of bombesin-positive tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Prostate cancer is a serious threat to men's health so it is necessary to develop technics for early detection of this malignancy. The purpose of this research was the evaluation of a new 99m Tc-labeled GnRH analogue as an imaging probe for tumor targeting of prostate cancer., Methods: 99m Tc-labeled-DLys6-GnRH analogue was prepared based on HYNIC as a chelating agent and tricine/ EDDA as coligands for labeling with 99m Tc. HYNIC was coupled to epsilon amino group of DLys6 through aminobutyric acid (GABA) as a linker. Radiochemical purity and stability in normal saline and serum, were determined by TLC and HPLC methods. Furthermore, calculation of protein-binding and partition coefficient constant were carried out for 99m Tc labeled peptide. The cellular experiments including receptor binding specificity and affinity were studied using three prostate cancer cell lines LN-CaP, DU-145 and PC-3. Finally, the animal assessment and SPECT imaging of radiolabeled GnRH analogue were evaluated on normal mice and nude mice bearing LN-CaP tumor., Results: The GnRH conjugate was labeled with high radiochemical purity (~97%). The radiolabeled peptide showed efficient stability in the presence of normal saline and human serum. The in vitro cellular assays on three prostate cancer cell lines indicated that the radiotracer was bound to LN-CaP cells with higher affinity compared to DU-145 and PC-3 cells. The Kd values of 99m Tc- HYNIC (tricine/ EDDA)-Gaba-D-Lys6GnRH were 89.39±26.71, 93.57±30.49 and107.3±18.82 in LN-CaP, PC-3 and DU-145 cells respectively. The biodistribution studies in normal mice and LN-CaP tumor-bearing nude mice showed similar results including rapid blood clearance and low radioactivity accumulation in non-target organs. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor uptake was 1.72±0.45 %ID/g at 1h p.i. decreasing to 0.70±0.06%ID/g at 4h p.i. for 99m Tc-HYNIC-Gaba-D-Lys6GnRH. The maximum tumor/ muscle ratio was 2.30 at 1h p.i. Pre-saturation of receptor using an excess of unlabeled peptide revealed that the tumor uptake was receptor mediated. The results of the SPECT image of LN-CaP tumor were in agreement with the biodistribution data., Conclusion: Based on this study, we suggest LN-CaP as a favorable cell line for in vivo studies on GnRH analogues. Moreover, this report shows that 99m Tc-HYNIC (tricine/EDDA)-Gaba-D-Lys6GnRH may be a suitable candidate for further evaluation of prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The significant role of midwives in providing labor and delivery care underscores the necessity of the identification of attitudes and beliefs of these groups of maternity care providers toward physiological childbirth. The purpose of the current study was to describe midwives' attitudes and beliefs toward physiological childbirth and identify its related factors., Methods: This cross-sectional study was carried out on 200 midwives working in the labor and delivery wards of selected hospitals in an urban area of Tehran, Iran, through the continuous sampling method from May to July 2018. The data were collected using a two-part demographic characteristic form and Midwives' Attitudes and Beliefs Questionnaire-Revised toward physiological childbirth. Data analysis was performed in SPSS software (version 25). The significance level was set at P < 0.05., Results: The mean score of midwives' attitudes and beliefs toward physiological childbirth were 119.90 with a standard deviation of 9.30. Moreover, of the different domains of Midwives' Attitudes and Beliefs Questionnaire-Revised, the women's experience of birth (78.53) and the medical model conflict (51.05) obtained the highest and lowest scores, respectively. According to the multiple linear regression model analysis, the total mean score of midwives' attitudes and beliefs toward physiological childbirth was significantly correlated with the level of education and interest in the profession (P < 0.05). Midwives with a master degree obtained higher scores (4.32) in terms of attitudes and beliefs toward physiologic childbirth, compared to those with an associate or bachelor degree. Also, there were 0.09 increases in the attitude and belief score of midwives per one score increase in their interest in the profession. It can be concluded that these two variables explained 16% of the variation in the scores of midwives' attitudes and beliefs to physiological childbirth., Conclusion: The results of this study showed that midwives with higher levels of education and more interest in their profession had more positive attitudes and beliefs toward physiological childbirth. Therefore, it is necessary to motivate midwives to obtain higher levels of education and increase their interest in the profession to promote physiological childbirth.

While the differentiation factors have been widely used to differentiate mesenchymal stem cells (MSCs) into various cell types, they can cause harm at the same time. Therefore, it is beneficial to propose methods to differentiate MSCs without factors. Herein, magnetoelectric (ME) nanofibers were synthesized as the scaffold for the growth of MSCs and their differentiation into neural cells without factors. This nanocomposite takes the advantage of the synergies of the magnetostrictive filler, CoFe 2 O 4 nanoparticles (CFO), and piezoelectric polymer, polyvinylidene difluoride (PVDF). Graphene oxide nanosheets were decorated with CFO nanoparticles for a proper dispersion in the polymer through a hydrothermal process. After that, the piezoelectric PVDF polymer, which contained the magnetic nanoparticles, underwent the electrospun process to form ME nanofibers, the ME property of which has the potential to be used in areas such as tissue engineering, biosensors, and actuators., (© 2019 Wiley Periodicals, Inc.)

Targeting overexpressed receptors on the cancer cells with radiolabeled peptides has become very important in nuclear oncology in the recent years. Peptides are small and have easy preparation and easy radiolabeling protocol with no side-effect and toxicity. These properties made them a valuable tool for tumor targeting. Based on the successful imaging of neuroendocrine tumors with 111 In-octreotide, other receptor-targeting peptides such as bombesin (BBN), cholecystokinin/gastrin analogues, neurotensin analogues, glucagon-like peptide-1, and RGD peptides are currently under development or undergoing clinical trials. The most frequently used radionuclides for tumor imaging are 99m Tc and 111 In for single-photon emission computed tomography and 68 Ga and 18 F for positron emission tomography imaging. This review presents some of the 99m Tc-labeled peptides, with regard to their potential for radionuclide imaging of tumors in clinical and preclinical application., (© 2018 John Wiley & Sons A/S.)

Background and Objective: Doxorubicin (DOX), despite having antitumor properties, also exhibits cardiotoxicity. Resveratrol has antitumor property for breast cancer cells. 99m Tc-MIBI has higher absorption rate in human breast cancer cell line MCF-7. In the present study, the authors intend to investigate the effect of DOX and resveratrol on the absorption of 99m Tc-MIBI in breast cancer cell xenografts in mice., Materials and Methods: Sixteen xenograft models in nude mice were divided into four groups. Group I (S, control) received 2% DMSO in 0.9% saline, group II (D) 2.5 mg/kg DOX, group III (D + R) 20 mg/kg/d resveratrol with 2.5 mg/kg DOX (total dose of 15 mg/kg in six injections), and group IV (R) 20 mg/kg/d resveratrol for 2 weeks. Single-photon emission computed tomography (SPECT) images were taken for the determination of 99m Tc-MIBI absorption. Mice were sacrificed, and the percentage of injected dose per gram (%ID/g) of the heart, liver, tumor, and muscle was measured using a gamma counter. Hematoxylin-eosin staining and Masson's trichrome staining were used for investigation of histopathological changes., Results: The %ID/g of tumor was lowest in group D + R. The severity of tumor necrosis or apoptosis was highest in group D + R, but there is no significant difference in pathological injuries and %ID/g of tumor between the group D + R and group D. In addition to the results of the %ID/g, the severity of pathological injuries to the liver and heart cells in group D + R was higher compared with group D. There is a significant difference in the %ID/g of the liver between the group D + R and group D. SPECT images showed that the lowest amount of %ID/g was observed in the tumor of group D + R., Conclusions: According to the results of pathology, biodistribution study, and imaging, the combination of DOX and resveratrol has shown higher antitumor effect; hence, 99m Tc-MIBI can be used to evaluate their antitumor effect.

Introduction: The aim of this study was to evaluate the ability of D (LPR), a novel retro-inverso peptidomimetic derivative for imaging colon cancer., Methods: Two different D (LPR) analogs were designed and compared based on conjugation of HYNIC at peptide's C or N terminal and then labeled with technetium-99m using tricine/EDDA as an exchange coligands. The radiolabeled conjugates were assessed for in vitro stability in saline and serum. The VEGFR-1 and NRP-1 receptors affinity, in vitro internalization and also dissociation Constance was evaluated. SPCET imaging and biodistribution studies were performed in nude mice bearing HT-29 xenograft tumors., Results: Both peptides labeled with technetium-99m in high radiochemical yield (˃97%). Peptide stability studies indicated a high metabolic stability of the radiopeptides in solution and serum. In vitro blocking studies demonstrated specific binding and internalization of [ 99m Tc]Tc-HYNIC-peptides in cultured HUVEC cells. The K d value for 99m Tc-peptide 1 and 99m Tc-peptide 2 were found to be 56.8 ± 12.9 nM and 71.6 ± 17.9 nM respectively. The tumor to muscle ratio was significant at 0.5 and 1 h after injection (4.5 and 4 for 99m Tc-peptide 1 and 4.9 and 4.4 for 99m Tc-peptide 2 at 0.5 and 1 h p.i. respectively). SPECT imaging studies revealed that both radioconjugates had prominent activity accumulation in VEGFR-1 and NRP-1 expressing HT-29 tumors., Conclusion: This study is the first instance of using a radiolabeled retro-inverso peptide for tumor imaging which is a promising tool to improve the performance of fragile peptide probes in vivo as imaging agents and warrant further investigations in other peptide-target systems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB., Objective: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling., Methods: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT., Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one., Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

It has been shown that more than 75% of ductal pancreatic adenocarcinomas overexpressed neurotensin (NT) receptors. Overexpression of NT receptors has been reported in various human tumor types. Hence, a non-invasive diagnosis and staging method could be very beneficial. In this work, we describe radiolabeling and evaluation of new neurotensin analogues to target neurotensin receptor-positive tumors such as pancreatic carcinoma. Radiolabeling was performed at 95°C for 10 min using 99m Tc in the presence of tricine/EDDA exchange labeling. Radiochemical yield analysis involved ITLC and HPLC methods. A binding assay test was carried out in nine different concentrations of labeled neurotensin analogues in HT-29 cells. Radiopeptide-specific binding and internalization were studied in NT receptors expressing HT-29 cells. Biodistribution studies were performed in tumor-free BALB/c mice and HT-29 xenografted tumor-bearing nude mice. The peptide was efficiently labeled by 99m Tc with high radiochemical yields (>98%). The radioconjugate was thoroughly stable in the solution and human serum even for 24 hr. The radiolabeled peptide showed high affinity (32.66 ± 4.01 nm) and specificity internalization (>%18 after 4 hr) to HT-29 cells. The radiopeptide efficiently showed tumor size and location in tumor-bearing nude mice. In biodistribution, a receptor-specific uptake of radiopeptide was observed in neurotensin receptor-positive organs such as intestine. Uptake in the tumor was 4.59 ± 0.23% ID/g after 2 hr. Owing to excellent stability, high affinity, rapid blood clearance, low accumulation in non-target organs, and high uptake in tumor, the 99m Tc-HYNIC-peptide is a potential agent for targeting of NTR-overexpressing tumor cells in clinical surroundings. When successfully executed in the clinical surrounding, non-invasive imaging of NTR-positive tumors with 99m Tc-labeled new neurotensin analogues could facilitate therapy procedure and monitoring., (© 2017 John Wiley & Sons A/S.)

Background: Labeled RGD peptide that specifically targets ανβ3 integrin has great potential for the early diagnosis of malignant tumors.αvβ3 integrin receptors appear specifically more on the surface of glioblastoma (malignant glioma) cells rather than normal cells., Objective: The aim of this study was to identify a novel RGD that can be radiolabeled with99mTc with in vitro assessment of its targeting ability for U87MG human brain cancer cells., Method: Novel RGD was designed by Amino Acid retro-inversion technique. The peptide HYNIC conjugate was radiolabeled with 99mTc at 95°C for 10 min and radiochemical analysis was performed using ITLC and HPLC methods. The stability of the radiopeptide was checked in the presence of human serum at 37°C up to 24 h. Binding properties and internalization were studied with U87MG cells., Results: Novel HYNIC-RGD has shown high radiochemical purity over 98%. Radioconjugate binding and internalization in U87MG cells were high and specific (13.96% and 12.38% at 4 h respectively). The radiolabeled peptide revealed good affinity for glioblastoma cells (Kd =1.46 ±0.26nM)., Conclusion: The in vitro study demonstrated the targeting ability of novel 99mTc-HYNIC-RGD for glioblastoma cells. Therefore, more in vivo studies are required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)