99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-HT7 receptors.

BACKGROUND: The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT7R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT7R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT7R imaging agents.  METHODS: Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[99mTc(CO)3(H2O)3]+ and 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were applied for in vivo imaging in U-87 MG Xenografted models. RESULTS: Specific binding study indicates that 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can recognize 5-HT7R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99mTc(CO)3-[6] and 99mTc(CO)3-[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor's radiotracer uptake, indicating the binding of these radiotracers to the 5-HT7R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99mTc(CO)3-[6] and 99mTc(CO)3-[7] at 60 min was 3.33 and 3.88, respectively.  CONCLUSIONS: 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can visualize tumor in the U87-MG xenograft model  due to their affinity toward 5-HT7R.

Synthesis and evaluation of 99mTc-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5HT7 receptors.

Glioblastoma multiform (GBM) is one of the most aggressive tumors of the central nervous system in humans. GBM overexpresses serotonin-7 receptors (5-HT7Rs); hence, this study aims to develop 5-HT7R targeted radiotracers. Aryl piperazine derivatives can act as ligands for 5-HT7R. Therefore, compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were synthesized and radiolabeled with 99mTcN2+ core. Radiolabeled 6 and 7 (99mTcN-[6] and 99mTcN-[7]) were prepared with high radiochemical purity (RCP > 96%). They displayed high affinity toward U-87 MG cell line 5-HT7R. The calculated Ki for 99mTcN-[7] was lower than that of 99mTcN-[6] (14.85 ± 0.32 vs 22.57 ± 0.73 nM) which indicates the higher affinity of 99mTcN-[7] toward 5-HT7R. A molecular docking study also confirmed the binding of these radiotracers to 5-HT7R. The biodistribution study in normal mice revealed that 99mTcN-[7] has the highest brain accumulation at 30 min post-injection (0.54 ± 0.12 %ID/g) while the uptake of 99mTcN-[6] is much lower (0.14 ± 0.02 %ID/g). The biodistribution study in the xenograft model confirms that the radiotracers recognize the tumor site. 99mTcN-[6], and 99mTcN-[7] showed the highest tumor uptake at 1-hour post-injection (5.44 ± 0.58 vs 4.94 ± 1.65 %ID/g) and tumor-to-muscle ratios were (4.61 vs. 5.61). The injection of pimozide blocks the receptors and significantly reduces the tumor-to-muscle ratios at 1-hour post-injection to 0.81 and 0.31, respectively. In correlation with in vitro study, 99mTcN-[6] and 99mTcN-[7] visualize the tumor site in U-87 MG glioma xenografted nude mice and display the tumor-to-muscle ratios of 7.05 and 6.03.

Molecular Imaging of HER2 Expression in Breast Cancer patients Using the [99mTc] Tc-Labeled Small Peptide.

PURPOSE: The accurate determination of human epidermal growth factor receptor 2 (HER2) status can predict response to treatment with HER2-targeted therapy for HER2-positive breast cancer patients. [99mTc]Tc-HYNIC-(Ser)3-LTVPWY ([99mTc]Tc-HYNIC-LY) is a small synthetic peptide molecule targeting of the HER2 receptor. This clinical study evaluated the pharmacokinetic, dosimetry, and efficacy of [99mTc]Tc-HYNIC-LY for determining the HER2 status in primary breast cancer patients. MATERIALS AND METHODS: In total, 24 women with suspected primary breast cancer received an intravenous injection of approximately 20 µg (∼740 MBq) of [99mTc]Tc-HYNIC-LY. In the first 3 patients, blood levels of radioactivity were analyzed for pharmacokinetic evaluation and planar gamma camera imaging was conducted at 30 min and 1, 2, 4, and 24 hour after injection for dosimetry assessment. In the last 21 patients, planar imaging was performed at the baseline, as well as 1, 2, 3, and 4 hour, followed by single-photon emission computed tomography (SPECT) imaging after 4 hour to evaluate the tumor-targeting potential in primary lesions. RESULTS: Injection of [99mTc]Tc-HYNIC-LY was safe and well tolerated. Fast blood clearance provided high-contrast HER2 imaging within 1 to 4 hour. The highest absorbed radiation dose was found for kidneys (6.78E-03 ± 2.62E-04 mSv/MBq), followed by the heart (3.73E-03 ± 1.98E-04 mSv/MBq). The [99mTc]Tc-HYNIC-LY peptide was able to detect HER2 status in primary tumors at an acceptable level. CONCLUSION: The findings of this study indicated that [99mTc]Tc-HYNIC-LY SPECT is safe and feasible for the identification of HER2-positive lesions in primary breast cancer patients, and may provide an accurate and non-invasive modality for guiding HER2 targeted therapy.

The Influence of Kidneys Ion Transport Inhibitors on the Pharmacokinetic and Tumor Uptake Behaviors of a HER2-targeted Small Size Radiolabeled Peptide.

BACKGROUND: HER2 over-expression plays a crucial role in the cancer treatment protocol. This study evaluates the effectiveness of organic anion and cation transport inhibitors and substrate on the tumor uptake of 99mTc- HYNIC-(Ser)3-LTVPWY radiotracer in SKOV-3 tumor-bearing nude mice. METHODS: Before the injection of the radiolabeled peptide, SKOV-3 tumor-bearing nude mice were treated with furosemide, cimetidine, para-amino hippuric acid, and saline. The inhibition effects of the organic anion and cation transport inhibitors were compared with the control group. In both treatment and control groups, the tumor and renal accumulation of radiopeptide in mice bearing SKOV-3 tumors were assessed in biodistribution and SPECT imaging studies. RESULTS: The biodistribution and imaging results suggested that all treated groups showed a higher tumor and higher normal tissue radioactivity compared to the control group. According to the tumor imaging study, the furosemidetreated group had slightly better tumor uptake and a higher tumor to muscle uptake ratio than other treatment groups. CONCLUSION: Administration of furosemide (an OAT inhibitor) increased radioactivity accumulation in the kidneys and blood and improved tumor radioactivity uptake. PAH (an anion transporter substrate) and cimetidine (an OCT inhibitor) have a minor effect on the accumulation of radioactivity in the kidneys and the acquired images.

The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines.

INTRODUCTION: Radiotherapy is one of the most common types of cancer treatment modalities. Radiation can affect both cancer and normal tissues, which limits the whole delivered dose. It is well documented that radiation activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway; hence, the inhibition of this pathway enhances the radiosensitivity of tumor cells. The mammalian target of rapamycin (mTOR) is a regulator that is involved in autophagy, cell growth, proliferation, and survival. CONCLUSION: The inhibition of mTOR as a downstream mediator of the PI3K/AKT signaling pathway represents a vital option for more effective cancer treatments. The combination of PI3K/AKT/mTOR inhibitors with radiation can increase the radiosensitivity of malignant cells to radiation by autophagy activation. Therefore, this review aims to discuss the impact of such inhibitors on the cell response to radiation.

Added diagnostic value of SPECT to evaluate bone metastases in breast cancer patients with normal whole body bone scan.

BACKGROUND: In this research, we aimed to survey the added value of single photon emission computed tomography (SPECT) in comparison with planar whole body bone scan to visualize bone metastatic lesions in patients with breast cancer. METHODS: A total of 80 patients with breast cancer (invasive ductal carcinoma) were examined with planar whole body bone scan and SPECT imaging using 99mTc-labelled methylene diphosphonate (99mTc-MDP). The patients with abnormal uptakes in SPECT imaging were also investigated with magnetic resonance imaging (MRI). RESULTS: Among these 80 patients with normal whole body bone SPECT scan, 19 (23.25%) of them revealed abnormal 99mTc-MDP uptake in skeleton. Furthermore, these 19 patients were subjected to MRI and 3 (3.75%) of them were confirmed with metastatic bone lesion. CONCLUSION: The obtained data suggest that SPECT possess the added diagnostic over planar whole body bone scan.

Data on the in vitro and in vivo anti-tumor effects of itraconazole, paclitaxel, and the two in combination in HT-29 and YM-1 cancer cell line and HT-29 colon cancer xenograft models.

Colon cancer is one of the fatal cancers in the world that metastatic potential and resistance to chemotherapy drugs are outstanding causes of cancer-induced mortality [1], [2], [3], [4]. We have investigated in vitro and in vivo anti-cancer effect of itraconazole and paclitaxel alone and their anti-cancer synergistic effect through MTT assay in YM-1 and HT-29 cell lines and in HT-29 tumor-bearing nude mice. Histopathological experiment was done for further assessment. Also, we evaluated the inhibitory effect of itraconazole on P-gp using specific in vivo biodistribution through 99mTc-MIBI uptake. 99mTc-MIBI, a myocardial perfusion imaging agent, is a useful radiotracer in diagnosis of some tumors and the liver and tumor accumulation of 99mTc-MIBI is changed by P-gp regulators [5], [6], [7], [8]. The data presented in this article are related to the research paper entitled "Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice". We hope our preliminary data to be helpful to design the chemotherapy regimen schedule with Itraconazole and Paclitaxel.

Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice.

P-glycoprotein (P-gp), is an important efflux pump involved in chemotherapy resistance in human colon cancer. We investigated the efficacy of itraconazole as a P-gp inhibitor and its therapeutic synergistic relationship to paclitaxel through 99mTc-MIBI accumulation in HT-29 tumor-bearing nude mice. Histopathological screening along with in vitro experiments was done for further assessment. Itraconazole successfully inhibited P-gp mediated 99mTc-MIBI efflux, increasing its in vitro accumulation in itraconazole-receiving dishes. Notably, the co-administration of itraconazole with paclitaxel significantly enhanced the in vitro cytotoxicity effect of paclitaxel in itraconazole + paclitaxel wells containing HT-29 cells. Compared to the control, tumor volume in mice treated with itraconazole, paclitaxel and itraconazole +paclitaxel showed growth suppression approximately by 36.21, 60.02, and 73.3% respectively. And compared to paclitaxel group, the nude mice co-treated with paclitaxel and itraconazole showed suppression of tumor growth by about 33.31 % at the end of the treatment period. Also the biodistribution result showed that the co-administration of itraconazole with paclitaxel raised the mean tumor radioactivity accumulation compared to control and paclitaxel group. When given paclitaxel alone, the ID% of hepatic and cardiac tissue was reduced while co-administration of itraconazole with paclitaxel increased 99mTc-MIBI accumulation in these organs. Furthermore, the histopathological findings confirmed the biodistribution results. These results demonstrate that although monotherapy with itraconazole or paclitaxel has anti-tumor activity against HT-29 human colorectal cancer, a synergistic anti-tumor activity can be achieved when itraconazole is co-administered with paclitaxel. Also, 99mTc-MIBI is an effective radiotracer for monitoring response to treatment in MDR tumors.

The effects of pharmacological interventions, exercise, and dietary supplements on extra-cardiac radioactivity in myocardial perfusion single-photon emission computed tomography imaging.

Myocardial perfusion imaging (MPI) as an imaging modality plays a key role in the monitoring of patients with cardiovascular disease. MPI enables the assessment of cardiovascular disease, the effectiveness of therapy, and viable myocardial tissue. However, MPI suffers from some downfalls and limitations, which can influence its clinical applications. These limitations can arise from the patient's condition, equipment, or the actions of the technologist. In this review, we mainly focused on the different effective parameters on radioactivity uptake of organs including liver, intestines, stomach, and gall bladder and how they affect the quality of the acquired images in nuclear medicine. More importantly, we cover how different suggested medicines, foods and exercise alleviative this problem.

Investigating the relationship between carotid intima-media thickness, flow-mediated dilatation in brachial artery and nuclear heart scan in patients with rheumatoid arthritis for evaluation of asymptomatic cardiac ischemia and atherosclerotic changes.

BACKGROUND: Cardiovascular disease is the most common cause of death worldwide. In order to prevent and treat heart diseases, we need to estimate the trend of non-cardiac diseases with the cardiovascular system. Arthritis Rheumatoid is a chronic immune/inflammatory process which leads to subclinical atherosclerosis and increases cardiovascular disease. We examined the patients who referred to our nuclear medicine center for MPI and correlated their findings with flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thickness (CIMT) in arthritis rheumatoid patients. MATERIAL AND METHODS: A total 30 known cases with arthritis rheumatoid were referred to our department for MPI and the single-photon emission computed tomography (SPECT) imaging were visually and quantitatively evaluated by two nuclear medicine physicians and the correlation of the measured FMD and CIMT were evaluated and compared with ultrasonography data. Demographic information such as gender, age and sex and medical history (risk factors, cardiovascular sign and symptoms, lab findings, medication etc…) were recorded in questionnaire sheets and were analyzed by SPSS.20. Chi-square and student t-test were used for further analysis. RESULTS: The mean CIMT (R = 0.452 ± 0.07, L = 0.447 ± 0.08) and %FMD (R = 7.22 ± 8.66, L = 6.42 ± 11.88) were measured for all subjects. Age was the only parameter correlated with both right and left CIMT (P = 0.033 and P = 0.024, respectively). Among the patients, 26.7% had mild ischemia (SSS < 8) and 3 of them suffered from active arthritis rheumatoid. All patients with RA showed normal ventricular ejection fraction and normal volumes and among them, 93.3% had normal functional performance (normal wall motion…). Moreover, the mean CIMT and %FMD were not significantly different in ischemic and non-ischemic patients. Among ischemic patients, just the course of the disease was associated with CIMT and none of the parameters was correlated with FMD. CONCLUSIONS: There is no significant statistical difference between ischemic and non-ischemic patients and also the functional performance with values of CIMT and FMD. Among all populations, the parameter of age, and in ischemic group, the course of disease were found as the only variable correlated with CIMT.

Preparation and evaluation of 99m Tc-HYNIC-D (TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with 99m Tc-HYNIC-EPPT.

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.

In vitro/in vivo assessment of the targeting ability of [99mTc] Tc-labeled an aptide specific to the extra domain B of fibronectin (APTEDB) for colorectal cancer.

OBJECTIVE: The APTEDB 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 [99mTc] Tc-APTEDB 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 (Kd) 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 APTEDB was efficiently labeled with technetium-99m in high radiochemical yield (up to 97%). Cellular binding study demonstrated specific binding of the [99mTc] Tc-APTEDB in cultured HT-29 cells. The Kd 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 [99mTc] Tc-APTEDB, which might be beneficial in design and development of new [99mTc] Tc-APTEDB for efficient targeting of tumor in vivo.

99mTc-radiolabeled HER2 targeted exosome for tumor imaging.

Exosomes represent unique features including nontoxicity, non-immunogenicity, biodegradability, and targeting ability that make them suitable candidates for clinical applications. Therefore, in this study, 99mTc-radiolabel HER2 targeted exosomes (99mTc-exosomes) were provided for tumor imaging. These exomes are obtained from genetically engineered cells and possessed DARPin G3 as a ligand for HER2 receptors. These exosomes were radiolabeled using fac-[99mTc(CO)3(H2O)3]+ synthon. The quality control showed high radiochemical purity (RCP) for 99mTc-exosomes (>96%). 99mTc-exosomes displayed a higher affinity toward SKOV-3 cells (higher HER2 expression) in comparison with MCF-7, HT29, U87-MG, A549 cell lines at different levels of HER2 expression. Trastuzumab (an antibody with a high affinity toward HER2) inhibited the binding of 99mTc-exosomes to SKOV-3 cells up to 40%. Biodistribution study in SKOV-3 tumor bearing nude mice confirmed the ability of 99mTc-exosomes for accumulation in the tumor. 99mTc-exosomes can visualize tumor in SKOV-3 tumor-bearing nude mouse. The blockage of HER2 receptors using trastuzumab (excessive amount) suggests the 99mTc-exosomes binding to the receptors and reduced the accumulation of 99mTc-exosomes in the tumor site. This suggest that 99mTc-exosomes interact with HER2 receptors and act through specific targeting.

99mTc-D(RGD): molecular imaging probe for diagnosis of αvß3-positive tumors.

OBJECTIVE: Arginine-glycine-aspartic acid (RGD) peptide with its specific binding affinity to integrin αvß3, is widely investigated for the development of molecular imaging probes for diagnosis of αvß3-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 (αvß3-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 αvß3-positive tumor in animal model. Therefore, further clinical and preclinical studies are required.

Novel 99mTc-2-arylimidazo[2,1-b]benzothiazole derivatives as SPECT imaging agents for amyloid-ß plaques.

Six novel 2-arylimidazo[2,1-b]benzothiazole (IBT) derivatives were synthesized as potential tridentate radiotracers for AD imaging purposes. Two of these ligands (6a,b) were successfully labeled with 99mTc radionuclide at high radiochemical purity using fac-[99mTc(CO)3(H2O)3]+ synthon. [99mTc]7a and [99mTc]7b were evaluated as single photon emission computed tomography (SPECT) imaging agents for Aß plaque in AD. [99mTc]7a and [99mTc]7b exhibited suitable affinity toward Aß aggregates with IC50 values of 33.2 and 102.5 nM, respectively. The IC50 value of these radiotracers depends on the length of the spacer (alkyl chain). In biodistribution study, these complexes showed good initial brain uptakes (0.78 and 0.86% ID/g at 2 min post-injection) and fast blood clearance. Autoradiography results confirmed that these small 99mTc complexes (Mw about 600 Da) can bind to Aß plaques in the brain sections of the rat AD model. Histopathological staining with Congo red approved the presence of Aß plaques in these brain sections.

THE QUANTITATIVE STUDY OF THE FACULTY MEMBERS PERFORMANCE IN DOCUMENTATION OF THE MEDICAL RECORDS IN TEACHING HOSPITALS OF MAZANDARAN UNIVERSITY OF MEDICAL SCIENCES.

INTRODUCTION: Documentation of patients' medical records has been always emphasized because medical records are as a means to be applied by patients, all medical staff, quality evaluations of health care, lawsuits, medical education and, etc. Regarding to this, each of the data elements available in the sheets of medical records has their own values. The rate of completion indicates the importance of the medical recorders for faculty member. So in this article the researcher evaluates the completion of medical records in the teaching hospitals of Mazandaran University of Medical Sciences. METHODS AND MATERIALS: This cross- sectional study has been conducted to review the patients' medical cases in five teaching university hospitals. To collect data, a check list was mode based on data element arrangement in four main sheets of admission and discharge, summery, patients' history and clinical examination and progress note sheets. Recorded data were defined as "Yes" with the value 1, not recorded data were defined as "No" with the value 2, and not used data were defined for cases in which the mentioned variable had no use with the value Zero. The overall evaluation of the rate of documentation was considered as %95 -100 equal to "good", 75-94% equal to average and under 75% was considered as "poor". Using the sample volume formula, 281 cases were randomly stratified reviewed. The data were analyzed by the software SPSS version 19 and descriptive statistical scales. RESULTS: The results have shown that the overall documentation rate in all the four sheets was 62% and in a poor level. There was no big difference in the average documentation among the hospital. Among the educational group, the gynecology and infection groups are equal to each other and had the highest record average (68%). Within the all groups, the highest rate has belonged to the documentation of signatures (91%). CONCLUSION: Regarding to the overall assessment that documentation rate was in a poor level, more attempt should be made to achieve a better condition. Even if a data element of the sheets seems meaningless, unnecessary and duplicated, it should not be ignored and skipped. In order to solve such problems, it is suggested that medical records sheets and the elements that seem unnecessary, should be reviewed in relevant committees.

Nuclear medicine for imaging of epithelial ovarian cancer.

Cancer is one of the leading causes of mortality worldwide. Usually, the diagnosis of cancer at an early stage is important to facilitate proper treatment and survival. Nuclear medicine has been successfully used in the diagnosis, staging, therapy and monitoring of cancers. Single-photon emission computed tomography and PET-based companion imaging agents are in development for use as a companion diagnostic tool for patients with ovarian cancer. The present review discusses the basic and clinical studies related to the use of radiopharmaceuticals in the diagnosis and management of ovarian cancer, focusing on their utility and comparing them with other imaging techniques such as computed tomography and MRI.

Epidemiology of tinea capitis in northeast Iran: a retrospective analysis from 1998 to 2012.

BACKGROUND: Tinea capitis is a common disease of the pediatric population. This disease typically follows one of several clinical patterns, i.e., scaling, hair loss, and/or inflammatory lesions, which are usually caused predominantly by two dermatophytic genera: Microsporum and Trichophyton. The aim of this study was to investigate tinea capitis and its etiological agents in Sari city of Mazandaran province, Iran. METHODS: We studied the spectrum of tinea capitis by means of a retrospective analysis involving 1745 patients referred to both the Reference Laboratory of Medical Mycology (RLMM) and Bo Ali Sina Hospital at Sari, Iran (1998-2012). Specimens were assessed by standard mycological techniques based on macroscopic and microscopic morphology. RESULTS: Among the patients, 480 (27.5%; 61 males and 39% females) were confirmed through a mycological examination. The peak incidence was in the 5-14 years age group. Endothrix (263 cases; 54.8%) was the most frequent clinical feature by direct exam. The predominant causative agents of tinea capitis were T. tonsurans (186 cases; 38.8%) and T. violaceum (119 cases; 24.8%), followed by T. mentagrophytes (46 cases; 9.6%), T. schoenleinii (28; 5.8%), T. rubrum (20 cases; 4.2%), M. gypseum (15 cases; 3.1%), T. verrucosum (14 cases; 2.9%), and Epidermophyton floccosum (1 cases; 0.2%). CONCLUSION: The present study showed that tinea capitis is mainly due to the anthropophilic species, and the most common species were T. tonsurans and T. violaceum. Owing to the high frequency of anthropophilic species, future studies may be useful in the development of preventive and educational strategies to reduce healthcare expenditure.

The 10-year Absolute Risk of Cardiovascular (CV) Events in Northern Iran: a Population Based Study.

BACKGROUND: The present study was conducted to estimate 10-year cardiovascular disease events (CVD) risk using three instruments in northern Iran. MATERIAL AND METHODS: Baseline data of 3201 participants 40-79 of a population based cohort which was conducted in Northern Iran were analyzed. Framingham risk score (FRS), World Health Organization (WHO) risk prediction charts and American college of cardiovascular / American heart association (ACC/AHA) tool were applied to assess 10-year CVD events risk. The agreement values between the risk assessment instruments were determined using the kappa statistics. RESULTS: Our study estimated 53.5%of male population aged 40-79 had a 10 -year risk of CVD events≥10% based on ACC/AHA approach, 48.9% based on FRS and 11.8% based on WHO risk charts. A 10 -year risk≥10% was estimated among 20.1% of women using the ACC/AHA approach, 11.9%using FRS and 5.7%using WHO tool. ACC/AHA and Framingham tools had closest agreement in the estimation of 10-year risk≥10% (κ=0.7757) in meanwhile ACC/AHA and WHO approaches displayed highest agreement (κ=0.6123) in women. CONCLUSION: Different estimations of 10-year risk of CVD event were provided by ACC/AHA, FRS and WHO approaches.

Vitamin E protects salivary glands dysfunction induced by ionizing radiation in rats.

The purpose of this study is to investigate the radioprotective effect of vitamin E as a natural product. Vitamin E protects the salivary glands dysfunction that is induced by ionizing radiation. It was analysed with radioisotope scintigraphy and then salivary gland to background counts ratio was calculated. Histopathological evaluation was performed. The rats were treated with vitamin E at dose of 400IU/kg 48, 24, and 1h before 15Gy gamma rays irradiation. The rats were evaluated for the salivary gland function through nuclear medicine protocol. Radiation causes significant salivary glands dysfunction at the 3rd and the 70th days with a reduction in radioactivity uptake in the salivary glands. Ratios of salivary gland to background radioactivities were 1.99±0.11, 1.58±0.08 and 1.92±0.04 for control, radiation, and vitamin E plus radiation groups, respectively. Vitamin E significantly improved salivary gland dysfunction induced by ionizing radiation in the rats. In conclusion, our results indicate protective effects of vitamin E against salivary gland dysfunction induced by gamma radiation. Thus, vitamin E is a promising radioprotective agent for patients who receive radiation in head and neck cancer therapy.