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Background: The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT 7 R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT 7 R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT 7 R imaging agents.  METHODS: Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + and 99m Tc(CO) 3 -[6] and 99m Tc(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, 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] were applied for in vivo imaging in U-87 MG Xenografted models., Results: Specific binding study indicates that 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] can recognize 5-HT 7 R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99m Tc(CO) 3 -[6] and 99m Tc(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-HT 7 R. 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 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] at 60 min was 3.33 and 3.88, respectively.  CONCLUSIONS: 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] can visualize tumor in the U87-MG xenograft model  due to their affinity toward 5-HT 7 R., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Objective: In the management of ST-segment elevation myocardial infarction (STEMI), if the treatment has not been initiated within the first 24 h and the patient no longer exhibits any symptoms, the decision to begin revascularization therapy is based on myocardial viability. If the tissue is nonviable, current guidelines advise against further revascularization therapy; however, collateral vessels represent an alternative source of blood supply and may help the damaged tissue to resume function; though at first, this tissue may not be considered viable. Thus, in patients whose first myocardial perfusion scintigraphy (MPS) revealed nonviable myocardium, a secondary MPS to assess viability may be beneficial and alter the course of treatment strategies., Methods: This prospective cohort study was conducted on 30 STEMI patients referred to Mazandaran Heart Center. If no myocardial viability was found using 99mTc-MIBI MPS, the patient was referred for a secondary MPS after 3 months., Results: In total, out of 30 patients, 3 became viable. There was no significant relationship between the viability of different Rentrop classes. Comparison of viability between patients with different numbers of occluded vessels showed no significant relationship. Three patients (17%) among 17 patients with Rentrop class nonzero became viable in the second MPS. Also, among four patients (13.3%) with Rentrop class three, one patient (25%) became viable and among seven patients (23.3%) with Rentrop class one, two patients (28.6%) became viable., Conclusion: Considering the results of this study, although nonsignificant, this subject requires further investigation to reach a definite conclusion., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Peptide receptor radionuclide therapy (PRRT) has evolved in cancer therapy and diagnosis. LTVSPWY, as a peptide, can target HER2 receptor; on the other hand, 177 Lu emits β - which is helpful for cancer therapy. The radiolabeling of LTVSPWY with 177 Lu results in a therapeutic agent ( 177 Lu-DOTA-LTVSPWY) capable of cancer treatment., Methods: 177 Lu-DOTA-LTVSPWY was prepared with high radiochemical purity (RCP). The stability was investigated in saline and human serum. The radiotracer affinity toward the SKOV-3 cell line with overexpression of the HER2 receptor was evaluated. Then the impact of the radiotracer on the colony formation of the SKOV-3 cell line was investigated with colony assay. Moreover, the biodistribution of this radiotracer in SKOV-3 xenograft tumor-bearing nude mice were also studied to determine the radiotracer accumulation in the tumor site. The mice were treated with 177 Lu-DOTA-LTVSPWY and subjected to histopathological evaluation., Results: The RCP of 177 Lu-DOTA-LTVSPWY after radiolabeling and stability tests was more than 97.7%. The radiotracer displayed high affinity toward the SKOV-3 cell line (K D  = 6.6 ± 3.2 nM). Treatment of the SKOV-3 cell line with the radiotracer reduces the SKOV-3 colony survival to less than 3% for 5 MBq of the radiotracer. Tumor-to-muscle (T/M) ratio is the highest at 48 h and 1 h post-injection (2.3 and 4.75, respectively). The histopathological study also confirms the cellular damage to the tumor tissue., Conclusions: 177 Lu-DOTA-LTVSPWY can recognize HER2 receptors in vivo and in vitro; hence, it can serve as a therapeutic agent., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: Ureteropelvic junction obstruction is a relatively common urologic problem in children. Most cases present with pelvicaliceal dilatation in antenatal period. Historically most UPJO cases were treated with surgical procedures, but recently many of these children have been treated by nonsurgical observational plans. We compared the outcome of children with UPJO treated in surgical and observational ways., Methods: In a retrospective study, we assessed the medical history of patients diagnosed as UPJO, march 2011 to march 2021. The case definition was based on grade 3-4 hydronephrosis and obstructive pattern in dynamic renal isotopes can. Patients were put into two groups; Group 1 children were treated with a surgical procedure, and group 2 patients without any surgical procedure for at least a six months' period after diagnosis. We assessed long-term events and improvement of obstruction., Results: Seventy-eight children (mean age 7.32mo., 80% male) enrolled in the study, 55 patients in group one and 23 as group 2. Severe hydronephrosis was the problem of 96% of all patients significantly led to 20% in group 1 and 9% in group 2 (P < 0.001). Severe kidney involvement was observed at 91% in group 1 and 83% in group 2, decreased to 15% and 6%, respectively (P < 0.001). There were no significant differences in sonographic and functional improvement between the two intervention groups. Long-term prognostic issues; growth, functional impairment, and hypertension were not different between the two groups, but group 1 children experienced more recurrence of UTI than group 2 patients., Conclusion: Conservative management is as effective as early surgical treatment in the management of infants with severe UPJO., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Hepatotoxicity remains amongst the restricting factors of Methotrexate (MTX)-associated cancer therapy, especially in high doses of chemo-drugs or prolonged treatment. Due to the known protective effects of Melissa officinalis (M. officinalis), the aqueous extract of this plant was evaluated to ameliorate MTX-associated hepatotoxicity in rats., Methods: Adult female Wistar rats were received or not M. officinalis aqueous extract at doses of 100 mg/kg (for 14 and 24 consecutive days) and 2 g/kg (for 14 consecutive days) by gavage technique. MTX (20 mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M. officinalis treatment. 24 h after the last day of treatment, 99m Tc-phytate was intravenously injected through the tail of rats. Animals were killed at 20 min after radiocolloid injection, and vital tissues including the liver and spleen were isolated, weighed, and their radioactivity was counted. As well, 99m Tc-phytate scintigraphy and histopathology of the liver were performed for higher accuracy., Result: A significant increase in liver radioactivity was detected in M. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100 mg/kg for 14 days. Also, a significant reduction in liver radioactivity was evident with M. officinalis extract at a dose of 2 g/kg for 14 days in comparison with the control group, this reduction was not significant at the lower dose of 100 mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect of M. officinalis vs MTX-induced liver injury in rats., Conclusion: In conclusion, we highlighted the liver uptake of 99m Tc-phytate as a valuable method for assessment of liver toxicity and addressed that M. officinalis pretreatment (100 mg/kg for 14 days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

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. [ 99m Tc]Tc-HYNIC-(Ser) 3 -LTVPWY ([ 99m Tc]Tc-HYNIC-LY) is a small synthetic peptide molecule targeting of the HER2 receptor. This clinical study evaluated the pharmacokinetic, dosimetry, and efficacy of [ 99m Tc]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 [ 99m Tc]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 [ 99m Tc]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 [ 99m Tc]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 [ 99m Tc]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., (Copyright © 2022 Elsevier Inc. 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.)

Purpose: The assessment of HER2 expression has a significant impact on optimizing cancer treatment protocol in patients. The aim of this study was to evaluate the potential usefulness of 99m Tc-HYNIC-(Ser) 3 -LTVPWY peptide for detecting HER2 alteration after paclitaxel therapy of ovarian tumor xenografts in nude mice. Materials and Methods: Mice bearing SKOV-3 tumors were treated with paclitaxel and saline. The antitumor efficacy of paclitaxel was compared with the control group in tumor size and histopathological examinations. In biodistribution and imaging studies, the tumor uptakes of radiolabeled peptide were evaluated in mice-bearing ovarian tumors in both groups. The HER2 expressions in transplanted tumors were analyzed by immunohistochemistry (IHC). Results: Tumor size gradually increased in all mice during the treatment, whereas tumors had considerably faster growth in the saline group compared to those in the paclitaxel-treated mice. Paclitaxel could suppress ovarian tumor growth and prevent vascular and cell proliferation in the tumoral mass. Biodistribution and imaging results demonstrated nonsignificant radionuclide accumulations in transplanted tumors in the paclitaxel- and saline-treated groups. IHC staining confirmed the HER2 status that was similar in both groups. Conclusions: The response of HER2 status to paclitaxel in mice bearing HER2-expression tumors was profitably monitored by HER2 targeted 99m Tc-HYNIC-(Ser) 3 -LTVPWY peptide that was agreement with IHC. The utilization of this radiolabeled peptide may be a valuable probe in evaluating HER2 status after chemotherapy.

We hypothesized that a novel design of the LTVPWY (LY) peptide might exhibit a great potential for improving binding affinity and targeting HER2-overexpressed tumors. Hence, new dimer construction of 99m Tc-labeled LY [ 99m Tc-HYNIC-E(SSSLTVPWY) 2 ] ( 99m Tc-DLY) was introduced. Afterward, a head-to-head comparison of in vitro and in vivo experiments was performed between 99m Tc-DLY and 99m Tc-HYNIC-SSSLTVPWY as the monomer analog. The blocking dosage of trastuzumab reduced the uptake of the dimer about 20% more efficiently than the monomer in the SKOV-3 cell line. A twofold increase in competitive binding affinity and biological half-life was observed for 99m Tc-DLY. The ovarian-tumor-bearing mice were detected with high contrast where the tumor-to-muscle ratio of 99m Tc-DLY was notably increased about 40% using a gamma camera. The biodistribution experiment revealed an approximately 10% enhancement in tumor/blood, tumor/muscle, and tumor/bone ratios for the dimer. More rapid blood clearance was another achievement of the homodimer design. Overall, 99m Tc-DLY successfully affected the pharmacokinetics and consequently the visualization of HER2-overexpressing tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage-associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross-talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process., (© 2022 Wiley Periodicals LLC.)

Purpose: Delivering care for immunocompromised, high-risk patients with cancer during a pandemic has proven challenging. Patients with cancer on chemotherapy have a high risk of mortality if contracted COVID-19. If a patient goes directly to the emergency room, multiple contact points with other individuals can lead to unnecessary exposures from any airborne virus, such as COVID-19. Our cancer center has implemented an isolated clinic with personal protective equipment and direct access to a COVID-19 rule-out floor to manage those with febrile neutropenia (FN)., Methods: We implemented an outpatient, isolated, extended-hour clinic with access to personal protective equipment, laboratories, and antibiotics for patients with FN as a pilot project from April 1 to December 31, 2020, with the aim to decrease emergency department (ED) visits for FN by 50%., Results: Since the implementation of our clinic, we have screened 74 unique patients during 102 visits, of which 76 led to a discharge and 26 led to a direct admit, thus avoiding the ED. Thirty-nine of these visits were for patients with recent travel or a known COVID-19 exposure. Bringing these patients to our isolated clinic ensured safety of the approximately 200 patients undergoing active treatment in our infusion center daily., Conclusion: Implementing this clinic has thus far successfully decreased the social footprint of our highest-risk patients with cancer in the ED considerably. Our efforts and hopes of decreasing the possible exposure of our immunocompromised patients to COVID-19 as well as the unnecessary exposure of the infusion center patients and personnel have thus far been effective., Competing Interests: Manidhar LekkalaStock and Other Ownership Interests: Pfizer, Editas Medicine¸ AbbVie, Teva, Atara Biotherapeutics Arpan PatelHonoraria: Medpage, AstraZeneca, Onc.AIResearch Funding: Onc.AI (Inst)No other potential conflicts of interest were reported.

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., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

With a poor prognosis, glioblastoma multiforme is the most aggressive tumor of the central nervous system in humans. The aim of this study was to develop novel tracers for the tumor targeting and imaging of overexpressed serotonin-7 receptors (5-HT 7 Rs) in U-87 MG glioma xenografted nude mice. Two phenylpiperazine derivatives named as PHH and MPHH were designed, and the corresponding radiotracers 99m Tc- PHH and 99m Tc- MPHH were synthesized in high radiochemical purity (>95%). 99m Tc- MPHH showed a higher affinity to 5-HT 7 Rs on U-87 MG cells compared to 99m Tc- PHH . In biodistribution studies, the radiocomplexes showed good brain uptake at 15 min combined with good radioactivity retention in the brain for 240 min. Regional rabbit brain studies indicated a higher radioactivity concentration in the hippocampus and diencephalon than in the cerebellum. Compared to 99m Tc- MPHH , the 99m Tc- PHH exhibited a significantly increased tumor uptake at 15 and 60 min, but the rapid blood clearance of 99m Tc- MPHH led to enhanced tumor-to-muscle ratios at 240 min. A significant reduction in tumor uptake 60 min after an injection of pimozide (5-HT 7 receptor antagonist) confirms the tumor uptake was receptor-mediated specifically. The tumor-to-contralateral muscle tissue ratio of 99m Tc- PHH and 99m Tc- MPHH in nude mice with U-87 MG xenograft was measured (5.25 and 4.65) at 60 min as well as (6.25 and 6.76) at 240 min, respectively.

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., (Copyright © 2020, Babol University of Medical Sciences.)

Background: The purpose of the present study was to assess the value of the fractional flow reserve (FFR) of the infarct-related artery (IRA) early after ST elevation myocardial infarction (STEMI) in detecting reversible ischemia., Methods: Single photon emission computed tomography (SPECT) at rest and after dipyridamole stress, and within 24 hour FFR of the IRA was performed on 69 patients 3 to 7 days after STEMI. FFR was 0.80 or less in 61 (88.4%) of them. In these patients, percutaneous coronary intervention (PCI) was performed, and a second SPECT study was repeated within 14 days., Results: SPECT showed reversible ischemia in 36 (59%) of these 61 patients, and converted to negative in 29 of them. Thus, the SPECT results of these 29 patients were defined as true positive before angioplasty and true negative after angioplasty. Considering the true-positive and true-negative SPECT results as the gold standard, the sensitivity, specificity, and positive and negative predictive values of the FFR of 0.80 or less compared to this gold standard were 96.7%, 100%, 100%, and 96.6%, respectively (ĸ = 0.97, P < 0.001)., Conclusions: In the early phase after STEMI, the reliability of FFR to determine residual ischemia in the IRA is very high in those patients with true-positive SPECT before and true-negative SPECT after PCI., Competing Interests: Disclosures None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The aim of this clinical trial was to evaluate the effects of febuxostat (FBX) in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in outpatients with moderate symptoms of COVID-19 infection., Methods: We conducted a clinical trial involving adult outpatients with the moderate respiratory illness following COVID-19 infection. Patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were needs to hospitalisation, clinical and laboratory data including fever, cough, breathing rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT findings were evaluated on admission and 14 days after initiation of treatment., Results: Sixty subjects were enrolled in the study with a 1 to 1 ratio in FBX and HCQ groups. On admission, fever (66.7%), cough (87%), tachypnoea (44.4%), dyspnoea (35%), elevated CRP value (94.4%) and lung involvement according to chest CT (100%) were documented in enrolled patients with insignificant difference between FBX and HCQ groups. Fever, cough and tachypnoea were significantly mitigated in both groups after five days of treatments without any significant differences between groups. The mean percentages of lung involvement were significantly reduced to 7.3% and 8% after 14 days of treatment with FBX and HCQ, respectively. In adult outpatients with moderate COVID-19 infection, the effectiveness of FBX and HCQ was not different in terms of resolution of clinical manifestations, laboratory tests and lung CT findings., Conclusion: This trial suggests that FBX is as an alternative treatment to HCQ for COVID-19 infection and may be considered in patients with a contraindication or precaution to HCQ., (© 2020 John Wiley & Sons Ltd.)

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.

Cornoid lamella is a definitive diagnostic feature of porokeratosis, a disorder of keratinization that has various different clinical presentations. A tiered column of parakeratosis and a diminished granular layer with dyskeratotic keratinocytes at the column base are all useful and known features of cornoid lamellation. We have found a cluster of vacuolated spinous cells to be a reliable fourth feature of cornoid lamellation and a feature when present alone to be a reliable sign of impending cornoid lamellation on deeper sections. Furthermore, we present a novel clinical phenotype of disseminated papular porokeratosis with effective clinical response to combination of phototherapy, oral and topical retinoids, and topical vitamin D derivative, which too contained all 4 features of cornoid lamellation.

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.)

Exosomes represent unique features including nontoxicity, non-immunogenicity, biodegradability, and targeting ability that make them suitable candidates for clinical applications. Therefore, in this study, 99m Tc-radiolabel HER2 targeted exosomes ( 99m Tc-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-[ 99m Tc(CO) 3 (H 2 O) 3 ] + synthon. The quality control showed high radiochemical purity (RCP) for 99m Tc-exosomes (>96%). 99m Tc-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 99m Tc-exosomes to SKOV-3 cells up to 40%. Biodistribution study in SKOV-3 tumor bearing nude mice confirmed the ability of 99m Tc-exosomes for accumulation in the tumor. 99m Tc-exosomes can visualize tumor in SKOV-3 tumor-bearing nude mouse. The blockage of HER2 receptors using trastuzumab (excessive amount) suggests the 99m Tc-exosomes binding to the receptors and reduced the accumulation of 99m Tc-exosomes in the tumor site. This suggest that 99m Tc-exosomes interact with HER2 receptors and act through specific targeting., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Early and accurate imaging of glioblastoma is of great value in staging, metastatic detection, treatment management and prognosis. The human epidermal growth factor receptor 2 (HER2) plays an essential role in the tumorigenesis and tumor progression in cancer. The aim of this study was to develop HER2-targeted peptide for glioma tumor imaging. Material and methods: HYNIC-(Ser) 3 -LTVPWY peptide was labeled with technetium-99m in presence of EDDA/tricine mixture as co-ligands. 99m Tc-HYNIC-(Ser) 3 -LTVPWY peptide was assessed for cellular specific binding and receptor-binding affinity. The biodistribution study and tumor imaging were conducted in nude mice bearing U-87 MG glioma xenografts. Results: The in vitro blocking study demonstrated specific binding of 99m Tc-HYNIC-(Ser) 3 -LTVPWY in cultured U-87 MG cells with a K D of 9.7 ± 2.0 nM. Biodistribution study revealed tumor to blood and tumor to muscle ratios were about 5.55 and 6.65 respectively after 1 h injection of radiolabeled peptide. Blocking study with non-labeled counterpart indicated a significant reduction (68%) in tumor uptake of 99m Tc-HYNIC-(Ser) 3 -LTVPWY that is indicated the tumor specificity of the radiolabeled peptide on glioblastoma. Gamma planar imaging revealed that the U-87 MG tumor was clearly visualized at 1 h. Conclusion: The results of this study showed that the 99m Tc-HYNIC-(Ser) 3 -LTVPWY peptide specifically accumulates in glioma and is, therefore, a promising probe for the diagnosis of glioma.

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.)

End-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) are cardiac volumes that have crucial roles in diagnosis of cardiovascular diseases (CVD) in patients. There are differences between these mentioned parameters in echocardiography (Echo) and myocardial perfusion scintigraphy (MPS) in clinical practice. In this study, we determined the nearest filtering parameters in the analysis of MPS data in comparison with three-dimensional echocardiography (3DE). All of patients were in this study, and 3DE and MPS were performed for all patients at rest phase in the same day. MPS images were analyzed through quantitative gated single photon emission computer tomography (SPECT) software with Butterworth filter which was a fixed order (order = 5) and variable cutoffs (COs) of 0.3, 0.35, 0.4, 0.45, and 0.5. The EDV, ESV, and EF values were measured by 3DE and MPS and compared. Based on the above different COs, the ESVs of MPS were 15.5 ± 18 mL, 18 ± 20 mL, 21 ± 22.5 mL, 22 ± 23 mL, and 22.5 ± 23.5 mL, respectively, while ESV of 3DE was 44.4 ± 23.5 mL. It was observed as a significant difference between MPS and 3DE for ESV. The EDVs of MPS were 61.3 ± 24.5 ml, 64 ± 26.5 ml, 68 ± 29.5 ml, 72 ± 31 ml, and 76 ± 32.2 ml, respectively, while EDV of 3DE was 105 ± 30 ml, which was significantly different between two methods. The EFs of MPS were 79% ± 14%, 76% ± 13%, 73.5% ± 12%, 73.5% ± 11%, and 74% ± 11%, respectively. The EF of 3DE was 58.4% ± 10% ml. It was statistically significant difference in values of EF between SPECT analysis parameters and 3DE. It was interesting when the COs increased from 0.3 to 0.5; the cardiac volumes increased while the EF decreased. The measured ESV and EDV values were lower in females than males while the EFs of females were higher than males. Finally, we demonstrate that the nearest Cos for measuring of EF and cardiac volumes for analysis of MPS data in comparison with 3DE are 0.45 and 0.5, respectively., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 World Journal of Nuclear Medicine.)

Hailey-Hailey disease (familial benign chronic pemphigus) is a genodermatosis with a typical clinical presentation of macerated plaques involving intertriginous areas of the body and affects multiple family members. Epidermal acanthosis, incipient, and completed acantholysis of many of the spinous keratinocytes of the epidermis and foci of dyskeratosis are well-recognized histologic findings. We have observed solitary lesions on the "scalp" of patients having a Hailey-Hailey-like pattern, and not the suprabasilar clefting of pemphigus represents the first manifestation of pemphigus vulgaris, which was confirmed with direct immunofluorescence in all our patients.

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.

Background: The intense liver uptake of technetium-99-sestamibi (Tc-MIBI) and photon scattering from the liver cause problems in quantitative perfusion interpretation. Hence, Tc-MIBI is a substrate for P-glycoprotein pump; variations in P-glycoprotein levels may affect liver clearance., Methods and Results: Adult female Wistar rats were divided into seven main groups [control and St. John's Wort (SJW) treated] and each SJW-treated group included three subgroups that were killed at 15, 30, and 45 min after Tc-MIBI injection. Treated groups received an SJW extract suspension at two doses of 100 and 400 mg/kg once daily for 5, 10, and 14 days, respectively. Tc-MIBI was injected intravenously to all rats 24 h after the final treatment. The rats were anesthetized at the mentioned time after tracer injection, and heart and liver tissues were removed, weighed, and their radioactivity was counted. One rat from each group was selected randomly for myocardial perfusion imaging. A significant increase in liver clearance and heart-to-liver ratio was observed in all SJW-treated groups compared with the control, especially at 10 days after SJW treatment. The heart radioactivity decreased in SJW-receiving groups at 14 days after SJW treatment., Conclusion: This study showed that SJW extract accelerates the liver clearance of Tc-MIBI and significantly reduces photon scattering from the liver.

The early diagnosis of non-small cell lung cancer (NSCLC) is important for increasing survival rate and improving quality life of patients. The aim of this study was to investigate 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 for targeting and imaging of NSCLC in A-549 xenografted nude mice. The (Ser) 3 -J18 peptide was conjugated with HYNIC and labeled with 99m  Tc using tricine as a co-ligand. The radiolabeled peptide was evaluated for its radiochemical purity, stability, receptor binding and internalization in vitro. The future experiments were performed for tumor targeting and imaging in A-549 tumor-bearing mice. 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 was obtained at high labeling efficiency at room temperature and favorable stability in saline and human plasma. At the cellular level, the radiolabeled peptide specifically bond to A-549 cells with a K D 4.1 ± 1.3 nM. Biodistribution study revealed tumor to blood and tumor to muscle ratios were about 3.12 and 5.63 respectively after 2 h injection of radiolabeled peptide. These ratios were significantly decreased by co-injection of excess non-labeled peptide in mice. This radiolabeled peptide selectively targeted to NSCLC tumor and exhibited a high target uptake combined with acceptable low background activity for tumor imaging in mice. The results of this study and its comparison with another study showed that 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 is better than previously reported radiolabeled peptide as 99m  Tc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 for NSCLC targeting and imaging., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Radiolabeled peptide could be a useful tool for the diagnosis of non-small-cell lung cancer (NSCLC). In this study, HYNIC-(Ser) 3 -J18 peptide was labeled with 99m Tc using EDDA/tricine as coligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular-specific binding and tumor targeting in A-549 cells and tumor-bearing mice, respectively. The high radiochemical purity was obtained and this radiolabeled peptide exhibited high stability in buffer and serum. The radiolabeled peptide showed high affinity for the A-549 cells with a dissociation constant value (K D ) of 4.4 ± 0.8 nm. The tumor-muscles ratios were 2.7 and 4.4 at 1 and 2 hr after injection of 99m Tc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 in tumor-bearing mice. The tumor uptake was decreased after preinjection with non-labeled peptide for this radiolabeled peptide in blocking experiment. The results of this study showed the 99m Tc-(EDDA/tricine)-(Ser) 3 -HYNIC-J18 peptide might be a promising radiolabeled peptide for NSCLC targeting., (© 2018 John Wiley & Sons A/S.)

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: Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99m Tc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor., Methods: The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99m Tc using tricine/EDDA co-ligand. The cellular specific binding of 99m Tc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice., Results: Radiochemical purity for 99m Tc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (K d ) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99m Tc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99m Tc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i., Conclusions: The 99m Tc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.

Overexpression of human epidermal receptor 2 (HER2) has given the opportunity for targeting and delivering of imaging radiotracers. The aim of this study was to evaluate the 99m Tc-HYNIC-(EDDA/tricine)-(Ser) 3 -LTVSPWY peptide for tumor targeting and imaging of tumor with overexpression of HER2. The HYNIC-(Ser) 3 -LTVSPWY was labeled with 99m Tc in presence of EDDA/tricine mixture as co-ligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular specific binding and tumor targeting. The high radiochemical purity of 99m Tc-HYNIC (EDDA/tricine)-(Ser) 3 -LTVSPWY was obtained to be 99%. It exhibited high stability in normal saline and human serum. In HER2 binding affinity study, a significant reduction in uptake of radiolabeled peptide (7.7 fold) was observed by blocking SKOV-3 cells receptors with unlabeled peptide. The K D and B max values for this radiolabeled peptide were determined as 3.3 ± 1.0 nM and 2.9 ± 0.3 × 10 6 CPM/pMol, respectively. Biodistribution study revealed tumor to blood and tumor to muscle ratios about 6.9 and 4 respectively after 4 h. Tumor imaging by gamma camera demonstrated considerable high contrast tumor uptake. This developed 99m Tc-HYNIC-(Ser) 3 -LTVSPWY peptide selectively targeted on HER2 tumor and exhibited a high target uptake combined with acceptable low background activity for tumor imaging in mice. The results of this study and its comparison with another study showed that 99m Tc-HYNIC-(EDDA/tricine)-(Ser) 3 -LTVSPWY is much better than previously reported radiolabeled peptide as 99m Tc-CSSS-LTVSPWY for HER2 overexpression tumor targeting and imaging., (Copyright © 2017 Elsevier Masson SAS. 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.)

Objectives: The monitoring of cancer treatment response to chemotherapy is considered an essential strategy for follow-up of patients. The aim of this study was to evaluate the use of 99m Tc-glucarate as a radiotracer for in vivo quantification and visualization of necrotic area and therapeutic effect of paclitaxel in ovarian cancer xenografted nude mice., Materials and Methods: After implantation of human ovarian cancer (SKOV-3) in nude mice, tumor xenografted mice were enrolled in two groups as control and treatment (paclitaxel) groups. 99m Tc-glucarate uptakes were quantified in tumors of control and treatment groups and also tumor imaging was performed with a gamma camera. The necrotic and viable areas of tumor and tumoral masses were evaluated through histopathological and macroscopic observations, respectively., Results: 99m Tc-glucarate uptake in tumor of treatment group was higher than control group. 99m Tc-glucarate uptake in ovarian tumor was clearly visualized with gamma imaging in both groups, but paclitaxel treated group showed higher radioactive uptake than control mice. The necrotic area in tumoral mass of mice treated with paclitaxel was confirmed by histopathological observations., Conclusion: 99m Tc-glucarate is an effective radiotracer for evaluation and monitoring of tumor necrosis caused by chemotherapy, and it may be helpful for therapy monitoring in patients with cancer.

In this study, we investigated the protective effect of vitamin E against methotrexate (MTX)-induced hepatotoxicity by quantitative liver 99mTc-phytate uptake and liver imaging and to compare its effect with histopathology in rat. Rats were divided into five groups as control, solvent, Vit E (100 mg/kg), MTX (20 mg/kg), Vit E + MTX and. Vit E was intraperitoneally administrated for 17 days before MTX injection and continued for 4 days. 99mTc-phytate was injected through the tail of rats after the drug administration. The percentage of the injected dose per gram of liver and spleen tissues (%ID/g) was calculated. Liver imaging was obtained with gamma camera. In other experiment, liver of treated rats were assessed for histopathology. 99mTc-phytate uptake per gram tissue of the livers as %ID/g in control, solvent, MTX, Vit E, Vit E + MTX and MTX groups were 8.99% ± 1.37, 8.53% ± 2.91, 8.65% ± 3.84, 3.22% ± 1.09 and 8.38% ± 2.68. Vit E administration with MTX resulted in a significant increasing in the level of %ID/g. Vit E treatment improved the shape of live in planner image. Histophatological examinations showed a protective effect of Vit E against MTX-induced hepatoxicity in rats. The results showed that Vit E significantly attenuates the MTX-induced hepatotoxicity in rats, and 99mTc-phytate uptake in liver as well as liver image to be acceptable techniques for assessment of liver and spleen damages and/or their tissues protective effects in animal model.

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: Breast cancer is a malignant disease with high mortality rate among women in the world. It is necessary to diagnose breast cancer at the early stage before it metastasizes in patients., Objective: The aim of this study is the evaluation of 99mTc-(tricine)-HYNIC-Lys-FROP for breast tumor imaging., Method: Lys-FROP peptide was labeled with 99mTc using HYNIC as chelator and tricine as co-ligand. Specific binding of this radiolabeled peptide on breast cancerous cell was assessed in different cell lines as well as in tumor-bearing mice., Results: HYNIC-Lys-FROP peptide was labeled with 99mTc at radiochemical purity more than 99%. It was observed high stability in normal saline and serum about 95%. The highest cellular uptake was observed in MCF-7 breast tumor cells treated with 99mTc-(tricine)-HYNIC-Lys-FROP as compared to other cell lines (lung, ovarian, T47D breast cancer cell lines). Biodistribution results in female MCF-7 tumor-bearing mice showed the relatively high tumor uptake and tumor-muscle ratio as 3.82 ± 0.66 after 15 min post-injection of 99mTc-(tricine)- HYNIC-Lys-FROP. Tumor uptake was reduced in mice that were co-injected with excess of unlabeled peptide to be 0.91 ± 0.08., Conclusion: Findings showed this radiolabeled peptide is a promising candidate for tumor targeting and molecular imaging of breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Urinary tract infection occurs in 1.8-6.6% of children under 6 years old. The aim of this study was to assess the urinary concentrations of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1), in children with acute pyelonephritis (APN) and the potential to develop renal scarring., Material and Methods: Children who had experienced an episode of APN were divided into 2 groups. Group 1 included children with APN who exhibited scarring and group 2 included children with APN who had a normal 99m Technetium dimercaptosuccinic acid scan. Urinary levels of MMP9 and TIMP1 were measured in the acute phase of infection. A receiver operating characteristic curve was generated to allow calculation of cut-off values., Results: Sixty-one children were enrolled across the 2 groups: group 1 contained 16 patients (all female); group 2, 38 children (36 female and 2 male). Urinary levels of MMP9 and TIMP1 were significantly higher in group 1 than in group 2 (p=0.037 and 0.022 respectively). For comparison of groups 1 and 2, the cut-off values were measured as 75.5 ng/mL (sensitivity 62.5%, specificity 71.1%, positive predictive value, PPV, 48%, negative predictive value, NPV, 82%), 16.1 ng/mL (sensitivity 75%, specificity 55.3%, PPV 41%, NPV 84%), and 1310.7 ng/mL (sensitivity 75% specificity 60.5%, PPV 44%, NPV 85%) for MMP9, TIMP1, and MMP9×TIMP1 levels, respectively., Conclusion: Evaluation of urinary MMP9 and TIMP1 levels may help to identify children with APN who are at risk of developing renal scarring., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Background: D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR)., Objective: The aim of study was to investigate the 99mTc-labeled D4 peptide for non-small cell lung tumor targeting., Method: HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabeled peptide was evaluated by blocking test on human non-small cell lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice., Results: This conjugated peptide was labeled with 99mTc in high radiochemical purity and it was highly stable in buffer and serum. The un-blocked to blocked cellular radioactivity ratio was 4- fold that showed a specific binding of this radiolabeled peptide on A-549 cell. Animal biodistribution in A-549 xenografted nude mice showed rapid clearance from blood and other non-target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 2.47% and 1.30% at 1 and 4 h after injection., Conclusion: This study showed the 99mTc-EDDA/tricine-HYNIC-(Ser)3-D4 peptide had tumor targeting on the non-small cell lung tumor., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Ovarian cancer is a serious threat for women health and the early diagnosis of this cancer might improves the survival rate of patients. The use of the targeted radiopharmaceuticals could be a non-invasive and logical method for tumor imaging. The aim of this study was to radiolabel GE11 peptide as a new specific probe for imaging of ovarian tumor., Methods: HYNIC-SSS-GE11 peptide was labeled with 99m Tc using tricine as a coligand. The 99m Tc-tricine-HYNIC-SSS-GE11 peptide was evaluated for specific cellular binding in three cell lines with different levels of EGFR expression. Tumor targeting was assessed in SKOV3 tumor bearing mice., Results: By using tricine as a coligand, labeling yield was more than 98% and the stability of the radiolabelled peptide in human serum up to 4 h was 96%. The in vitro cell uptake test showed that this radiolabeled peptide had a good affinity to SKOV3 cells with dissociation constant of 73 nM. The in vivo results showed a tumor/muscle ratio of 3.2 at 4 h following injection of 99m Tc-tricine-HYNIC-SSS-GE11 peptide., Conclusions: Results of this study showed that 99m Tc-tricine-HYNIC-SSS-GE11 peptide could be a promising tool for diagnosis and staging of ovarian cancer. 99m Tc-tricine-HYNIC-SSS-GE11, a novl targeted agent for ovarian tumor imaging.

Peptides are a class of targeting agents that bind to cancer-specific cell surfaces. Since they specifically target cancer cells, they could be used as molecular imaging tools. In this study, the 15-mer peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was conjugated with HYNIC via lysine amino acid on C-terminus and labeled with 99m Tc using tricine and EDDA/tricine as the co-ligands. These radiotracers were evaluated for potential utilization in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined based on their binding on an ovarian cancer cell line (SKOV-3), and displaying a low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistribution studies were conducted in normal mice as well as in nude mice bearing SKOV-3 ovarian cancer xenografts. HYNIC-peptide was labeled with 99m Tc with more than 99% efficiency and showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27%±0.46% and 1.55%±0.20% for tricine and 2.34±1.1% and 1.09%±0.18% for EDDA/tricine at 1 and 4h after injection, respectively. A higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide. This new 99m Tc-labeled peptide selectively targeted ovarian cancer and introduction of a (EDDA/tricine) as a co-ligand improved the pharmacokinetics of 99m Tc-labeled H1299.2 for tumor imaging in animals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: In this study, radiolabeled D4 peptide conjugate was studied as a radiotracer for imaging of non-small-cell lung cancer with overexpression of EGFR., Methods: HYNIC-(Ser)3-D4 peptide was labeled with 99m Tc using tricine as a co-ligand. Cellular specific binding and internalization as well as in vivo tumor targeting were assessed., Results: The in vitro experiments showed good cellular specific binding. Tumor uptake values as %ID/g were 7.55 and 6.82% at 1 and 4 h after injection, respectively. The presaturation of EGFR in xenografted nude mice reduced 36% tumor uptake of radioactivity at 1 h after injection that confirmed in vivo specificity., Conclusion: Findings showed this radiolabeled peptide is a promising candidate for tumor targeting and molecular imaging of non-small-cell lung cancer.

Nanobodies are important biomolecules for tumor targeting. In this study, we synthesized and labeled anti-epidermal growth factor receptor (EGFR) nanobody OA-cb6 with 99m Tc(CO) 3 + and evaluated its characteristics for targeting the EGFR in the A431 human epidermal carcinoma cell line. Nanobody radiolabeling was achieved with high yield and radiochemical purity, and the radioconjugate was stable. Biodistribution results in nude mice exhibited a favorable tumor-to-muscle ratio at 4-hr postinjection, and tumor location was visualized at 4 hr after injection of radiolabeled nanobody. Our result showed that the OA-cb6- 99m Tc-tricarbonyl radiolabeled nanobody is a promising radiolabeled biomolecule for tumor imaging in cancers with high EGFR overexpression., (© 2016 John Wiley & Sons A/S.)

The high expression of the human epidermal growth factor receptor 2 (HER2) and the accessibility of its extracellular domain make it an ideal target for the targeted delivery of anti-tumor drugs as well as imaging agents. In this study, the heptapeptide leucine-threonine-valine-serine-proline-tryptophan-tyrosine (LTVSPWY) as a new small peptide for an anti-HER2 target was labeled by incorporating 99m Tc to the cysteine-based ligands CGGG (Cys-Gly-Gly-Gly) and CSSS (Cys-Ser-Ser-Ser) linked to this peptide. Both 99m Tc-labeled peptides were evaluated for HER2 bindings as well as pharmacokinetics and tumor targeting. CGGG- and CSSS-LTVSPWY peptides were labeled with 99m Tc using a gluconate ligand exchange. Cellular specific binding, affinities, and internalization of both peptides to the HER2 receptor were evaluated in the SKOV-3 cell line. Specific targeting of both peptides to the HER2 receptor was assessed in three cell lines with different levels of HER2 expression. Studies were performed in SKOV-3 tumor bearing mice for tumor targeting. Both peptides were labeled with 99m Tc with more than 99% efficiency and showed favorable stability in solution and serum. The HER2 binding affinities of both the radiolabeled peptides were inhibited up to 60% by the unlabeled peptide, as well as with trastuzumab antibody. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 4.95 ± 4.84% and 3.84 ± 2.53% for the CSSS and CGGG chelators, respectively, at 1 h after injection. However, tumor uptakes were similar for both peptides at 4 h postinjection, although a higher tumor to background ratio and lower radioactivity retention in the kidney were observed for CSSS, leading to a clearer tumor image with injection of this peptide. These small new peptides were selectively targeted to the HER2 receptor, and introduction of a serine residue into the chelator improved the pharmacokinetics of 99m Tc labeled LTVSPWY for clear tumor imaging in animals., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Acquiring a high quality image has assigned an important concern for obtaining accurate diagnosis in nuclear medicine. Detector is a critical component of Single Photon Emission Computed Tomography (SPECT) imaging system for giving accurate information from exact pattern of radionuclide distribution in the target organ. The images are strongly affected by the attenuation, scattering, and response of the detector. The conventional detector is mainly made from sodium iodide activated by thallium [NaI(Tl)] in nuclear medicine imaging., The Aim of the Study: This study has planned to introduce a suitable for an optimized SPECT imaging. SIMIND Monte Carlo program was utilized for simulating a SPECT imaging system with a NaI(Tl) detector, and a low-energy high-resolution (LEHR) collimator., Material and Methods: The Planar and SPECT scans of a 99mTc point source and also an extended Cardiac-Torso (XCAT) computerized phantom with the experiment and simulated systems were prepared. After verification and validation of the simulated system, the similar scans of the phantoms were compared from the point of view of image quality for 7 scintillator crystals including: NaI(Tl), BGO, YAG:Ce, YAP:Ce, LuAG:Ce, LaBr3 and CZT. The parameters of energy and spatial resolution, and sensitivity of the systems were compared. Images were analyzed quantitatively by SSIM algorithm with Zhou Wang and Rouse/Hemami methods, and also qualitatively by two nuclear medicine specialists., Results: Energy resolutions of the mentioned crystals obtained were: 9.864, 9.8545, 10.229, 10.221, 10.230, 10.131and10.223 percentage for 99mTc photopeak 140 Kev, respectively. Finally, SSIM indexes for the related phantom images were calculated to 0.794, 0.738, 0.735, 0.607, 0.760 and 0.811 compared to the NaI(Tl) acquired images, respectively. Medical diagnosis of the SPECT images of the phantom showed that the system with BGO crystal potentially provides a better detectability for hot and cold lesions in the liver of XCAT phantom., Conclusions: The results showed that BGO crystal has a high sensitivity and resolution, and also provides a better lesion detectability from the point of view of image quality on XCAT phantom.