Tumor Microenvironment Features as Predictive Biomarkers in Metastatic Differentiated Thyroid Cancer and Their Relationship With 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Metabolic Parameters.

OBJECTIVE: The role of the tumor microenvironment in tumor progression and treatment response is being investigated for different types of cancer. This study aimed to determine the relationships between tumor microenvironment, histopathology, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based metabolic parameters, treatment response, and overall survival (OS) in metastatic differentiated thyroid cancer (DTC).  Methods: Metastatic DTC patients who underwent 18F-FDG PET/CT between 2015-2019 were evaluated. Clinicopathological, histopathological features and PET/CT parameters of patients were recorded. Microenvironmental characteristics of the primary tumor, such as mitosis, intratumoral and peritumoral lymphocytosis, intratumoral and peritumoral fibrosis, were evaluated from the tissue samples. The relationships between these factors were statistically analyzed. RESULTS:  Sixty-five patients (38 females, 27 males, age: 49±15 years) were included. Mitosis, intra/peritumoral lymphocytosis, and intra/peritumoral fibrosis were frequent; however, none of them had a statistically significant association with PET-positive metastases, treatment response, or OS. Univariate analysis showed that gender, size, thyroglobulin values, residual thyroid tissue, PET-positive metastases, and maximum standardized uptake value (SUVmax) were significant predictors of OS. At multivariate analysis, PET-positive metastases (HR=-2.65, 95%CI 0.007-0.707, p=0.024) and SUVmax (HR=-2.74, 95%CI 0.006-0.687, p=0.023) were the only independent predictors for OS.  Conclusion: Our study revealed that microenvironmental characteristics of the primary tumor did not show prognostic significance in metastatic DTC. PET-positive metastases and SUVmax levels were the only significant factors that predicted overall survival in DTC. Supporting the results of our study with further studies with a larger sample size may be necessary to determine the relationship between the tumor microenvironment and prognosis in DTC.

Development of a Radiolabeled Folate-Mediated Drug Delivery System for Effective Delivery of Docetaxel.

Many preclinical studies are carried out with the aim of developing new formulations for the effective delivery of taxane class drugs, one of the most important anticancer drugs used clinically today. In this study, a radiolabeled folate-mediated solid lipid magnetic nanoparticle (SLMNP) system was developed by loading superparamagnetic iron oxide nanoparticles (MNP) and docetaxel (DTX) into the solid lipid nanoparticles as a drug delivery system that will function both in cancer treatment and diagnosis. For this purpose, first, SLMNP was synthesized by the hot homogenization method, and the surface of the particles was modified with a folate derivative to carry the particles to tissues with folate receptors. The synthesized magnetic solid lipid nanoparticles were loaded with DTX, and then radiolabeling was carried out with technetium-99 m (99mTc-DTX-SLMNP). Structural characteristics of these nanoparticles were determined by characterization methods. According to the TEM images of MNPs, SLN, and SLMNPs, MNPs were observed between 25and 35 nm, SLNs between 400 and 500 nm, and SLMNPs between 350 and 450 nm. The drug entrapment efficiency of SLMNPs loaded with DTX was found to be 19%, and the percentage efficiency of radiolabeling was found to be 98.0 ± 2.0%. The biological behavior of this radiolabeled system was investigated in vitro and in vivo. Folate receptor-positive SKOV-3 and folate receptor-negative A549 cancer cell lines were studied. The IC50 values of DTX-SLMNP in SKOV-3 and A549 cells were 50.21 and 172.27 µM at 48 h, respectively. Gamma camera imaging studies of 99mTc-DTX-SLMNP and magnetically applied 99mTc-DTX-SLMNP compounds were performed on tumor-bearing CD-1 nude mice. The uptake in the folate receptor-positive tumor region was higher than that in the folate receptor negative tumor region. We proposed that the drug delivery system we prepared in this study be evaluated for preclinical studies of new drug carrier formulations of the taxane class of anticancer drugs.

PET/CT for Early Detection of COVID-19 Pneumonia: Diffuse Fluorodeoxyglucose Uptake in the Lungs without any Additional Changes in a Patient with Breast Cancer

Coronavirus disease-2019 (COVID-19), which causes infections in the upper and lower respiratory tract, became a pandemic shortly after it was first diagnosed in Wuhan city, China. Many people are affected with high mortality rates and severe respiratory distress syndrome. During this pandemic, all physicians paid attention to the findings of COVID-19. Suggestive findings in 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) were characterized as increased 18F-FDG uptake in bilateral peripheral consolidative areas and ground glass opacities. We aimed to show diffuse FDG uptake in PET images with indefinable lesions in CT as a suspicious finding for early COVID-19.

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.

OBJECTIVE: 68Ga-PSMA-PET/CT is a relatively new technique, that is rapidly becoming widespread. We aimed to contribute interobserver-intraobserver agreement of 68Ga-PSMA-PET/CT, among low/high-experienced interpreters. METHODS: 68Ga-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 κ: 0.84/0.84, high-experienced 0.89/0.96; LN2 low-experienced κ: 0.88/0.79, high-experienced 0.95/0.95; LN3 low-experienced κ: 0.84/0.89, high-experienced 0.87/0.94, first/second readings, respectively) and bone lesions (low-experienced κ: 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 (κ: 0.74/0.89, first/second readings, respectively), and was moderate-substantial among a low-experienced group (κ: 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 (κ: 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 68Ga-PSMA-PET/CT requires training with a small number of identified cases.

The Diagnostic Contribution of SPECT/CT Imaging in the Assessment of Gastrointestinal Bleeding: Especially for Previously Operated Patients.

OBJECTIVES: Gastrointestinal bleeding (GIB) is a life-threatening problem that requires a multidisciplinary approach for successful treatment. This study aims to emphasize the clinical contribution of single photon emission computed tomography/computed tomography (SPECT/CT) for the diagnosis of acute bleeding. METHODS: All 14 patients referred to the nuclear medicine department in 3 years with suspicion of acute GIB were evaluated retrospectively. Clinical records were analyzed to assess the scintigraphic findings, emphasizing the correlative contribution of the CT portion on SPECT/CT studies. RESULTS: Five patients were negative on dynamic and static planar images. SPECT/CT was performed in 9 patients who had positive findings on planar imaging. SPECT/CT could identify the same bleeding site originating from the anastomosis in four patients with a history of abdominal surgery. SPECT/CT confirmed bleeding from the cecum in a patient with cervical cancer. SPECT/CT showed the bleeding focus in the bladder neck of a patient with bladder cancer and the bleeding from peritoneal metastases of a patient with gastric cancer. In 1 patient, the right upper quadrant activity accumulation, which may cause false positives, was found to be the gallbladder on SPECT/CT. Delayed images showed the true bleeding focus in the cecum. In 1 patient, suspicious activity accumulation in the midline of the abdomen was found to be due to a previously unknown aortic aneurysm on SPECT/CT. CONCLUSION: SPECT/CT imaging is a feasible technique to facilitate image interpretation in patients with GIB. SPECT/CT imaging can guide the surgeon through more accurate localization. Therefore, for proper patient management, SPECT/CT should be applied to detect the bleeding focus, if present, especially in patients who had undergone a previous operation.

Sarcopenia in Hodgkin's lymphoma evaluated with 18-FDG PET/CT, focus on age, performance, and treatment.

Sarcopenia is defined as a progressive and generalized muscle disorder associated with certain physiological and pathological conditions. We aimed to evaluate the prevalence of sarcopenia in patients with HL using 18-fluoro deoxyglucose (FDG) PET/CT, which would provide a data of muscle mass with the CT compartment and also data of muscle metabolism with the 18-FDG compartment of the imaging modality. Fifty-nine patients diagnosed with HL were included in the study. PET/CT images before and after treatment were evaluated with regard to lumbar muscle mass and metabolism. Mean lumbar muscle evaluation with CT before treatment was 92, 40 HU, and after treatment was 89, 41 HU. Mean metabolic tumor volume (MTV) evaluated with FDG PET before treatment was 4, 13 mm3 while after treatment was 4, 10 mm3. The lumbar muscle mass in terms of HU which was evaluated with CT was observed to be decreased after treatment. Likewise, the metabolic evaluation was observed to be also decreased after treatment. Despite the decline in muscle mass after treatment in the whole group, this decline was particularly observed in the better initial performance group. In patients with BMI > 32, there was a significant decline in muscle mass. Abdominal nodal involvement was related with poorer muscle mass and quality. In HL care, particular attention should be given to patients who are younger and with better physical condition in terms of preserving the muscle reserves and preventing sarcopenia.

Animal Models for the Evaluation of Theranostic Radiopharmaceuticals.

BACKGROUND: 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. 131I treatment and scintigraphy are the best examples of the theranostic application. Likewise, 177Lu / 90Y octreotate for neuroendocrine tumors, 177Lu PSMA for metastatic or treatment-resistant prostate cancer, 90Y SIRT for metastatic liver cancer, and 223Ra for bone metastasis of prostate cancer are widely used. Moreover, nanoparticles 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.

Evaluation of Sarcopenia with F-18 FDG PET/CT and relation with disease outcomes in patients with multiple myeloma.

INTRODUCTION: Multiple myeloma (MM) is a potentially incurable haematological malignancy with devastating manifestations including lytic bone lesions leading to fractures and renal insufficiency. As a disease of patients with a mean age of 66 years, both the disease and the continuous efforts of treatments lead to frailty and devastation. From this stand point, we aimed to evaluate the development of muscle loss in MM patients and also with a new method of sarcopenia evaluation, F-18 FDG PET/CT. While used for bone disease routinely, this method brings a fresh perspective of metabolic quantitation of alteration of muscles which may be regarded as muscle quality. MATERIALS AND METHODS: Data and images of 105 patients with MM both before and after treatment were evaluated in a retrospective manner. RESULTS: Both female and male patients were observed to be effected after MM treatment in terms of lumbar and femoral muscle evaluations with CT. Metabolic evaluations confirmed a loss of quality in muscles in terms of metabolic volume and total lesion glycolysis. CONCLUSION: Sarcopenia should be evaluated in every patient and regarded as a treatment target. FDG PET/CT is an easy and handy tool to assess muscle mass and quality as well as MM disease status.

The relationship between FDG PET/CT-defined metabolic parameters and the histopathological subtype of oesophageal carcinomas.

PURPOSE: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) combined with computed tomography (CT) scan is accepted as a standard tool in the staging of oesophageal cancer (OC). Histological subtype of tumour is known to be a major determinant of prognosis and metabolic behaviour. In this study, we aimed to evaluate the effect of histological subtypes of OC on standard uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) obtained by PET/CT, and also to compare this effect with prognosis. MATERIAL AND METHODS: Images and clinical course data of 57 patients who were diagnosed with EC and treated in our hospital between 2009 and 2016 were evaluated in a retrospective manner. PET/CT images were re-analysed in terms of metabolic parameters, and observations were compared with histological subtypes. RESULTS: No significant difference was observed between histological subtypes with SUVmax, overall survival (OS), or progression-free survival (PFS). Thus, MTV was observed to be related with histological subtype; MTV values of adenocancer patients were significantly higher than those of squamous cell cancer patients. CONCLUSIONS: Metabolic tumour volume was related with histological subtype of OC, but clinical staging, TLG, and SUVmax values were not related with histological subtype, which may suggest the use of MTV as a routine parameter for OC and inclusion of MTV observations in prognostic scoring.

Combined effect of parathyroid hormone and strontium ranelate on bone healing in ovariectomized rats.

OBJECTIVE: Parathyroid hormone (PTH) enhances bone healing. Strontium ranelate (SR) is an antiresorptive agent that increases bone formation. Reports about combined effects of PTH and SR on local bone regeneration in osteoporotic subjects are limited. We aimed at investigating the efficacy of PTH and SR for promoting new bone formation in critical-sized defects of ovariectomized rats. MATERIALS AND METHODS: Parathyroid hormone- and/or SR-containing poloxamer implant tablets with/without chitosan microparticles were delivered locally to calvarial defects of 90 Wistar rats. Biopsies were analyzed histologically and histomorphometrically at 4 and 8 weeks of healing. RESULTS: Histomorphometry revealed that PTH alone promoted new bone formation at 4 weeks but the efficiency declined in 8 weeks. There was no positive effect of SR alone on bone formation at 4 or 8 weeks. Calvarial defects treated with PTH+SR combinations showed statistically significant greater new bone formation than either treatment alone at both time intervals. Tissue responses were modest and supported the good biocompatibility of the biomaterials used. CONCLUSION: Parathyroid hormone and SR combinations can be effective for calvarial bone regeneration of ovariectomized rats. PTH plus SR may have potential use as bone graft material in orthopedic and dental surgery to enhance bone healing and osseointegration.

18F-FDG PET/CT Imaging of Burkitt Lymphoma Presenting With Unusual Muscle Involvement.

Extranodal involvement is more common with Burkitt lymphoma (BL) than other subtypes of non-Hodgkin lymphoma in childhood. According to our knowledge, there are rare cases in the literature about muscle involvement of BL, and its F-FDG PET/CT findings were not well defined. We report a 6-year-old girl with a histopathologic diagnosis of BL and referred for staging with PET/CT. FDG-avid abdominal lymph nodes and diffuse involvements of right quadriceps muscle were demonstrated.

Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC.

Breast 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 99mTc-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.

Comparison of protective effects of L-carnitine and amifostine on radiation-induced toxicity to growing bone: histopathology and scintigraphy findings.

PURPOSE: 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 (300 mg/kg) and amifostine (200 mg/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.

Effects of strontium ranelate, raloxifene and misoprostol on bone mineral density in ovariectomized rats.

OBJECTIVES: 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, 2 g, Servier, Istanbul), 1800 mg/kg/day; misoprostol (Cytotec, 200 mcg, Ali Raif, Istanbul), 200 mcg/kg/day; raloxifene (Evista, 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.

Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats.

1. The 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. 2. 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. 3. 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). 4. Based on the results of the present study, L-carnitine and amifostine have comparable and significant protective effects against radiation-induced late nephrotoxicity.

Glucose-induced alteration of accumulation of organotechnetium complexes accumulation in Pgp-negative tumor-bearing mice.

The 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.

A new imaging modality in detection of caustic oesophageal injury: Technetium-99m pyrophosphate scintigraphy.

OBJECTIVES: 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 h after the burning experiment. Anterior static and single-photon emission computed tomography images were obtained using a low-energy all-purpose collimator, 2.55 zoom factor, 3h 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 (O) 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.

The effects of methylene blue on renal scarring due to pyelonephritis in rats.

The 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.

Clearance of technetium-99m-labeled DTPA in hyperthyroidism without clinical evidence of lung disease, and relation to pulmonary function.

OBJECTIVE: The mechanisms of dyspnea and exercise intolerance have not been fully elucidated. We aimed to investigate the clearance rate of technetium-99m diethyltriaminepentaaceticacid (Tc-99m DTPA) from lungs in hyperthyroid patients without clinical evidence of lung disease and to explore the interactions between their Tc-99m DTPA radioaerosol lung scintigraphy, spirometric measurements, and the levels of thyroid hormones. METHODS: We studied 19 hyperthyroid patients and 16 sex- and age-matched controls. Thyroid hormone levels were assessed. Spirometric lung function tests, diffusing capacity of the lung for carbon monoxide (DLCO) and the clearance rate of Tc-99m DTPA were performed in all participants. Ratio of DLCO value to the alveolar ventilation (DLCO/VA) and the means of half-time (T1/2) of Tc-99m DTPA clearance rate, which were used to evaluate alveolar-capillary membrane permeability, were calculated. RESULTS: There were no statistical differences between spirometric parameters (VC, FVC, FEV1/FVC, FEF 25-75) of the two groups (p > 0.05). Although the mean FEV1 level was significantly lower in the hyperthyroid patients than the control subjects (p < 0.01), in five patients FEV1 was only less than 80 percent of the predicted value. No significant difference in the means of DLCO, DLCO/VA or T1/2 values of Tc-99m DTPA clearance was observed between the two groups (p > 0.05). In hyperthyroid patients, there was a positive relation between DLCO/VA, DLCO/VA % and T1/2 values of Tc-99m DTPA clearance (p < 0.01, r = 0.732, p < 0.01, r = 0.742, respectively). The lung volumes and the levels of thyroid hormones did not show a significant relationship to T1/2 values of Tc-99m DTPA clearance in hyperthyroid group (p > 0.05). CONCLUSIONS: We conclude that increased thyroid hormones have no effect on permeability of alveolar-capillary membrane in hyperthyroid patients.

Use of iodine-123 metaiodobenzylguanidine scintigraphy for the detection of amiodarone induced pulmonary toxicity in a rabbit model: a comparative study with technetium-99m diethyltriaminepenta acetic acid radioaerosol scintigraphy.

The purpose of the study was; (i) to determine whether 123I-MIBG scintigraphy is sensitive for detection of amiodarone induced pulmonary toxicity (AIPT) and (ii) to compare it with 99mTc-DTPA radioaerosol. Twelve white New Zealand rabbit with initial mean body weight 4.24 +/- 0.47 g were divided into two groups. AIPT group (n = 7) was administered amiodarone (20 mg/kg BW). The control group (n = 5) received the same amount of 0.9% saline. All animals underwent 123I-MIBG and 99mTc-DTPA radioaerosol scintigraphy at the end of the treatment period. 123I-MIBG static thorax images were obtained during 10 minutes at 15 minutes and 3-hours after intravenous injection of the radiopharmaceutical. Lung to heart ratios (LHR) and lung to mediastinum ratios (LMR), and retention index (LRI) of 123I-MIBG were determined. Two days after 123I-MIBG scintigraphy, 99mTc-DTPA radioaerosol scintigraphy was performed, and clearance from the lungs was measured for 10 min (1 min/frame) following termination of inhalation. 123I-MIBG lung retention index (LRI) was significantly higher in the AIPT group than the control (61 +/- 4.6 vs. 40 +/- 4.5, p = 0.01). Early LHR and LMR were significantly lower in the AIPT group than in the control group (p = 0.04, p = 0.01, respectively), whereas those of late LHR and LMR were not significantly different. T1/2 values of DTPA clearance were significantly increased in AIPT group according to the control group (55 +/- 7.2 vs. 86.6 +/- 18.5, p = 0.02). 123I-MIBG scintigraphy is a valuable tool for detecting AIPT in a rabbit model. Additionally, 99mTc-DTPA radioaerosol scintigraphy is an excellent comprehensive investigational tool for detecting AIPT with the added advantage of lower cost.