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Öğe 68Ga-PSMA-I&T-PET/CT interobserver and intraobserver agreement for prostate cancer: a lesion based and subregional comparison study among observers with different levels of experience(Lippincott Williams & Wilkins, 2021) Soyluoglu, Selin; Korkmaz, Ulku; Ozdemir, Busra; Ustun, Funda; Durmus-Altun, GulayObjective Ga-68-PSMA-PET/CT is a relatively new technique, that is rapidly becoming widespread. We aimed to contribute interobserver-intraobserver agreement of Ga-68-PSMA-PET/CT, among low/high-experienced interpreters. Methods Ga-68-PSMA-PET/CT of 56 patients with prostate cancer were evaluated blindly by four observers. Visual interpretation of malignant disease and SUVmax for lymph node (LN) regions, local tumor, bones and visceral organs were recorded. Cohen's Kappa and Fleiss' Kappa analyses were used to measure agreement between low/high/all-experienced observers. Variations were compared for regions, and the effect of prostate-specific antigen or Gleason score on the results was investigated. Results Interobserver agreement was almost perfect for all LN regions (LN1 low-experienced kappa: 0.84/0.84, high-experienced 0.89/0.96; LN2 low-experienced kappa: 0.88/0.79, high-experienced 0.95/0.95; LN3 low-experienced kappa: 0.84/0.89, high-experienced 0.87/0.94, first/second readings, respectively) and bone lesions (low-experienced kappa: 0.88/0.88, high-experienced 0.92/0.92, first/second readings, respectively). For local tumor, interobserver agreement was substantially-almost perfect among a high-experienced group (kappa: 0.74/0.89, first/second readings, respectively), and was moderate-substantial among a low-experienced group (kappa: 0.62/0.56, first/second readings, respectively). Intraobserver agreement was almost perfect for three observers for all regions and substantial for the observer with the lowest experience in LN3, local and visceral lesions (kappa: 0.74/0.79/0.62, respectively). Conclusion Interpretation of prostate-specific membrane antigen (PSMA) for prostate cancer is acceptably consistent among observers, but some details are noteworthy. The evaluation should be done more algorithmically for local tumors, since all observers showed relatively lower agreement. The agreement increased as prostate-specific antigen and Gleason score increased. The observer with PSMA experience <30 readings showed lower reliability, distinct from the others. This indicates that although a reader may be familiar with other PET agents, a more consistent interpretation of Ga-68-PSMA-PET/CT requires training with a small number of identified cases.Öğe Animal Models for the Evaluation of Theranostic Radiopharmaceuticals(Bentham Science Publ Ltd, 2021) Soyluoglu, Selin; Durmus-Altun, GulayBackground: Theranostic is a new field of medicine that combines diagnosis and patient-specific targeted treatment. In the theranostic approach, it is aimed to detect diseased cells by using targeted molecules using disease-specific biological pathways and then destroy them by cellular irradiation without damaging other tissues. Diagnostic tests guide the use of specific therapeutic agents by demonstrating the presence of the receptor/molecule on the target tissue. As the therapeutic agent is administered to patients who have a positive diagnostic test, the efficacy of treatment in these patients is largely guaranteed. As therapeutic efficacy can be predicted by therapeutic agents, it is also possible to monitor the response to treatment. Many diagnostic and therapeutic procedures in nuclear medicine are classified as theranostic. I-131 treatment and scintigraphy are the best exam- ples of the theranostic application. Likewise, Lu-177 / Y-90 octreotate for neuroendocrine tumors, Lu-177 PSMA for metastatic or treatment-resistant prostate cancer, Y-90 SIRT for metastatic liver cancer, and Ra-223 for bone metastasis of prostate cancer are widely used. Moreover, nanopartides are one of the most rapidly developing subjects of theranostics. Diagnostic and therapeutic agents that show fluorescent, ultrasonic, magnetic, radioactive, contrast, pharmacological drug or antibody properties are loaded into the nanoparticle to provide theranostic use. Methods: This article reviewed general aspects of preclinical models for theranostic research, and presented examples from the literature. Conclusion: To achieve successful results in rapidly accelerating personalized treatment research of today, the first step is to conduct appropriate preclinical studies.Öğe Comparison of Protective Effects of L-Carnitine and Amifostine on Radiation-induced Toxicity to Growing Bone: Histopathology and Scintigraphy Findings(Asian Pacific Organization Cancer Prevention, 2010) Yurut-Caloglu, Vuslat; Durmus-Altun, Gulay; Caloglu, Murat; Usta, Ufuk; Saynak, Mert; Uzal, Cem; Cosar-Alas, RusenPurpose: The aim of the present study was to evaluate the radioprotective efficacy of L-carnitine (LC) in growing bones in comparison to amifostine. Materials and Methods: Sixty two-week-old Wistar albino rats were randomly assigned to six equal groups: Group 1, control (CONT); Group 2, irradiation alone (RT); Group 3, amifostine plus irradiation (AMI+RT); Group 4, L-carnitine plus irradiation (LC+RT); Group 5, amifostine alone (AMI); Group 6, L-carnitine alone (LC). The rats in the AMI+RT, LC+RT and RT groups were irradiated individually with a single dose of 20 Gy to the left femur. LC (300mg/kg) and amifostine (200mg/kg) were applied 30 min before irradiation. The animals were scanned for bone area, mineral content and bone mineral density (BMD) by DEXA and the 99mTc methylene diphosphonate uptake ratio (MUR) was calculated by bone scintigraphy. Histopathological analysis of bone and cartilage was also carried out after euthanasia. Results: Pretreatment with LC or amifostine reduced the radiation-induced damage in growing bone (p=0.007 and p=0.04 respectively) and in the epiphysial cartilage (p=0.002 and p=0.015 respectively). The protective effect of LC was similar to that of amifostine on both growing bone and on the epiphysial cartilage. The mean left-femur BMD values were significantly higher in the LC+RT (p=0.02) and AMI+RT (p=0.01) groups than in the RT group. but did not differ with the two protective agents. Pretreatment with AMI (p=0.002) and LC (p=0.01) improved the MUR. Conclusions: L-carnitine is equally as effective as amifostine at protecting growing bone against single dose irradiation damage.Öğe The effects of methylene blue on renal scarring due to pyelonephritis in rats(Springer, 2007) Aksu, Burhan; Inan, Mustafa; Kanter, Mehmet; Puyan, Fulya Oz; Uzun, Hafize; Durmus-Altun, Gulay; Gurcan, SabanThe aim of this study was to evaluate the efficiency of methylene blue (MB) in preventing renal scar formation after the induction of pyelonephritis (PNP) in a rat model with delayed antimicrobial therapy. An inoculum of the K-12 strain of Escherichia coli was injected into both kidneys. Control groups received isotonic saline instead of bacterial solution. Four equal groups were then formed: the PNP group was untreated and the PNP ciprofloxacin (CIP) treated group was treated only with CIP intraperitoneally (i.p.) starting on the third day following bacterial inoculation. In the PNP (MB)-treated group, MB was given i.p., and in the PNP MB + CIP-treated group, MB + CIP were administered i.p.. In the sixth week following bacterial inoculation, all rats were sacrificed, and both kidneys of the rats in all groups were examined biochemically and histopathologically for renal scarring. Renal scar was significant in the groups treated with MB alone or MB + CIP combination compared with untreated or antibiotic only groups. Delayed treatment with antibiotics had no effect on scarring. These results suggest that the addition of MB to the delayed antibiotic therapy might be beneficial in preventing PNP-induced oxidative renal tissue damage.Öğe Effects of strontium ranelate, raloxifene and misoprostol on bone mineral density in ovariectomized rats(Elsevier Science Bv, 2009) Ahmet-Camcioglu, Nefise; Okman-Kilic, Tulay; Durmus-Altun, Gulay; Ekuklu, Galip; Kucuk, MustafaObjectives: To investigate the effects of strontium ranelate, raloxifene and misoprostol on bone mineral density (BMD) in ovariectomized rats to contribute to the individualization of the treatment of postmenopausal osteoporosis. Study design: Sixty sexually mature female Sprague-Dawley rats weighing 250 g were used. The 60 rats were divided into six groups of 10 rats each: SR, MISO, RAL, SHAM, DW and OVX All except the SHAM rats were subjected to bilateral ovariectomy. Three days after surgery, rats were administered strontium ranelate (Protelos (R), 2 g, Servier, Istanbul), 1800 mg/kg/day; misoprostol (Cytotec (R), 200 mcg, Ali Raif, Istanbul), 200 mcg/kg/day; raloxifene (Evista (R), 60 mg, Lily and Company, Istanbul), 3 mg/kg/day and 1 cc of distilled water by gavage for 8 weeks. Bone mineral density measurements were then performed. Results: The strontium ranelate (SR) group had significantly higher vertebral BMD than all other groups. Femoral density in the SR group was also significantly higher than in other groups and there was no difference between femoral density in the strontium ranelate and sham groups. Conclusions: Strontium ranelate, raloxifene and misoprostol can prevent bone loss in the vertebrae, whereas strontium ranelate can also prevent bone loss in the femur of ovariectomized rats. Strontium ranelate increases greater than raloxifene and misoprostol BMD in the vertebrae. Condensation: Strontium ranelate may increase both vertebral and femur BMD in ovariectomized rats while raloxifene and misoprostol may only increase lumbar spine BMD. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.Öğe Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC(Humana Press Inc, 2011) Ustun, Funda; Durmus-Altun, Gulay; Altaner, Semsi; Tuncbilek, Nermin; Uzal, Cem; Berkarda, SakirBreast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer. The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density (MVD), Doppler sonography (DS) and Tc-99m-Tetrofosmin (TF) uptake. Ehrlich ascites tumour cell xenografts, Pgp-negative tumour were divided into two groups: (a) Morphine sulphate [0.714 mg/kg/day (equivalent to 50 mg per day for a 70 kg human)], (b) no-morphine. For the determination of angiogenesis in mice tumour tissue, TF scintigraphy, microvessel density and DS were done. MVD was significantly different between groups (49.4 +/- 1.8 vs. 41.8 +/- 1.9, morphine and no-morphine groups, respectively, P < 0.001). A strong correlation was found between late uptakes of mass at scintigraphy and degree of angiogenesis in histopathologic examination (r = 0.52, P < 0.01). There was statistically significant inverse correlation between degree of angiogenesis in histopathologic examination and washout ratio of TF (r = 0.40, P < 0.05). The higher values for angiogenesis are related to higher TF reuptake. There was no statistically significant correlation between DS and TF. A strong correlation was found between MVD and grade of DS (r = 0.51, P < 0.01). Our preclinical mice study indicates that morphine at clinically relevant doses stimulates angiogenesis, and angiogenesis triggered of morphine is demonstrated with MVD and DS, but not TF. However, uptake and washout of TF are compared with immunohistochemically assessed morphine-stimulated angiogenesis in tumour tissue.Öğe Glucose-Induced Alteration of Accumulation of Organotechnetium Complexes Accumulation in Pgp-Negative Tumor-Bearing Mice(Mary Ann Liebert Inc, 2009) Ustun, Funda; Durmus-Altun, Gulay; Cukur, Ziya; Altaner, Semsi; Berkarda, SakirThe biologic and microenvironmental factors determining (99m)Tc sestamibi (MIBI) and (99m)Tc tetrofosmin (TF) uptake in breast tumors are incompletely understood, especially in P-glycoprotein (Pgp)-negative tumors. We analyzed the influence of glucose administration on the uptake and retention of MIBI and TF in Pgp-negative tumor-bearing mice in vivo. Twenty (20) mice bearing Ehrlich ascites tumor cell (EATC) xenografts were divided into four groups: (1) MIBI, (2) MIBI+glucose, (3) TF, and (4) TF+glucose. Glucose was administered (5.0 g/kg body weight) intraperitoreally (i.p.) 1 hour before scintigraphy. There were significant differences between the E-UPR MIBI and MIBI+glucose groups (p = 0.009) and minor differences in L-UPR between these groups (p = 0.04). There was a significant inverse correlation between E-UPR of MIBI and glucose levels (r = 0.71, p = 0.02). Comparing the four groups, the highest E-UPR was obtained in the MIBI group (p = 0.006). Other parameters were not different in the MIBI and MIBI+glucose groups and in the TF and TF+glucose groups. Increased blood glucose level affected the MIBI uptake of tumor tissue, particularly for E-UPR. We suggest that these findings were due to basically decreased blood flow and secondarily decreased extracellular pH. However, glucose administration did not affect TF.Öğe HISTOPATHOLOGICAL AND SCINTIGRAPHIC COMPARISONS OF THE PROTECTIVE EFFECTS OF l-CARNITINE AND AMIFOSTINE AGAINST RADIATION-INDUCED LATE RENAL TOXICITY IN RATS(Wiley-Blackwell Publishing, Inc, 2009) Caloglu, Murat; Yurut-Caloglu, Vuslat; Durmus-Altun, Gulay; Oz-Puyan, Fulya; Ustun, Funda; Cosar-Alas, Rusen; Saynak, MertThe aim of the present study was to compare the protective effects of l-carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., l-carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., l-carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (T(max)) and time from peak count to half count (T(1/2)) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T(1/2) of the right kidney was 8 +/- 2 and 21 +/- 2 min, respectively. The T(max) values for the AMI + RAD and LC + RAD groups (2.8 +/- 0.2 and 3.2 +/- 0.2 min, respectively) were similar to those in the control group (2.5 +/- 0.3 min). Based on the results of the present study, l-carnitine and amifostine have comparable and significant protective effects against radiation-induced late nephrotoxicity.Öğe A new imaging modality in detection of caustic oesophageal injury: Technetium-99m pyrophosphate scintigraphy(Elsevier Ireland Ltd, 2009) Aksu, Burhan; Durmus-Altun, Gulay; Ustun, Funda; Torun, Nese; Kanter, Mehmet; Umit, Hasan; Sut, NejdetObjectives: Early oesophagoscopy is usually recommended in children after caustic ingestion to assess the severity of the initial digestive lesions. An oesophagoscopic procedure in children always demands to be performed under sedation and bears a certain risk of iatrogenic injury. The purpose of the study is to determine the value and sensitivity of Tc-99m pyrophosphate (99mTc-PYP) scintigraphy for the detection of caustic oesophageal injury. Methods: The caustic oesophageal burns were created with 25% NaOH in an experimental rat model. Seventeen rats were divided into two groups. The BURN group (n = 9) included caustic oesophageal burning rats. Non-BURN group (n = 8) included sham-operated rats. All animals underwent 99mTc-PYP scintigraphy 72 In after the burning experiment. Anterior static and single-photon emission computed tomography images were obtained using a tow-energy all-purpose collimator, 2.55 zoom factor, 3 h after intravenous injection of 10 mCi 99mTc-PYP. After the imaging, all the oesophagi were explored for external determination of the injury sites and macroautoradiographic scintigraphy as well. Rectangular region of interest were placed in the visually determined lesion of oesophagus (0) as well as non-lesion area (N), and an ON ratio was created. The severity and extension of oesophageal burn were assessed 3 days after burning by histopathologic evaluation. The injuries were graded according to the ulcer depth, ulcer width, thrombus formation, and the development of perivascular fibrinoid necrosis. Results: The oesophageal burning areas were demonstrated by visual evaluation of the Tc-99m PYP scintigraphy on all animals. The mean ON ratio of 99mTc-PYP was 21.61 +/- 7.01 in the BURN group and in the non-BURN group, was 2.25 +/- 0.24 (p < 0.001). The best cut-off point of the ON ratio for caustic oesophageal injury was 5.45, with sensitivity and specificity of 100%. PYP scan findings were also confirmed by histological evidence of ulcer depth, ulcer width, thrombus formation, and perivascular fibrinoid necrosis in the same areas. Conclusions: The caustic oesophageal injuries have been demonstrated by 99mTc-PYP scintigraphy in burning experiment. 99mTc-PYP scintigraphy is sensitive for detection of caustic oesophageal injury. This new imaging tool is found to be sensitive and specific for the detection of caustic oesophageal injury in the rats. Published by Elsevier Ireland Ltd.Öğe Small cell carcinoma of the prostate: case report and a review of the literature(Kare Publ, 2010) Denizli, Bengu; Yurut-Caloglu, Vuslat; Caloglu, Murat; Karagol, Hakan; Kaplan, Mustafa; Durmus-Altun, Gulay; Oz-Puyan, FundaSmall cell carcinoma of the prostate is a very rare and aggressive tumor, which accounts for 0.5-2% of all prostate carcinomas. Signs and symptoms include obstructive, neurologic and constitutional symptoms like bone pain, abdominal pain, hematochezia, and hematuria later followed by symptoms of paraneoplastic syndromes like ectopic ACTH secretion and inappropriate ADH secretion and myasthenic syndrome. Approximately, 75% of patients have advanced disease at diagnosis. The small number of patients in the literature prevents a consensus for an optimal treatment option. Because small cell carcinomas of the prostate and lung are identical, treatment options are similar. Chemotherapy is the mainstay of the treatment. Cisplatin/etoposide chemotherapy is frequently used. External radiotherapy is used with combination chemotherapy for local control in the limited disease, as well as for palliation in extensive disease. This report describes management of a 76-year-old patient with an advanced stage small cell carcinoma of the prostate in light of the reviewed literature.