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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The incidence of recurrence and hypothyroidism after radioiodine treatment in patients with hyperthyroidism in Trakya, a mild iodine deficiency area, during the period 1991-2003.

OBJECTIVE: The purpose of this retrospective study was to evaluate the incidence of recurrence and the success of radioiodine treatment (RIT) in the Trakya region of Turkey, an area with mild iodine deficiency, and to compare the effect of dose regimen selection (fixed (FD) or calculated dose (CD)) on treatment success. MATERIAL AND METHODS: The study sample included 148 patients (40 male, median age 50) treated with radioiodine between the years 1991-2003. Patients were categorized into three diagnostic groups: Graves' disease (GD) (n = 65), solitary toxic adenoma (TA) (n = 29), and toxic multinodular hyperthyroidism (TMH) (n = 54), and each divided into two subgroups according to treatment method; the first group was treated with a FD of 370 MBq (10 mCi), and the second with CD. RESULTS: The largest group was GD (44%), followed by TMH (36%). Median duration of follow-up was 28 months (range 6-147). FD was given to 52.7% of all patients and CD was given to 47.3%. There was a partial difference in the dose regimen between all groups, but did not reach statistically significant levels (FD vs. CD: 65%-35%; 38%-62%; 46%-54%; GD, TA, TMH respectively, p > 0.05). Total cure rate in FD and CD was 46 (59%) and 37 (52.9%), respectively. The rates of hypothyroidism for GD, TA, and TMH groups were 28 (43.1%), 6 (20.7%) and 16 (29.6%), respectively. The incidence of hypothyroidism did not vary significantly between any groups (p > 0.05). At the end of the follow-up period, a total of 104 patients (70.3%) were treated successfully. There was no significant difference in the cure rate between any groups (p > 0.05). CONCLUSIONS: The treatment success in all groups and subgroups did not differ significantly between FD and CD. Our lower cure rate than in previous studies may be related to iodine deficiency. Higher doses of radioiodine may be required to increase final treatment success in endemic goiter areas. If this true, dosimetry and calculated dose regimen would be required in all groups of patients instead of an FD concept. However, our findings should be verified in larger series of patients, with longer follow-up period, and urinary iodine concentration measurements.

The protective effect of amifostine on radiation-induced acute pulmonary toxicity: detection by (99m)Tc-DTPA transalveolar clearances.

PURPOSE: The purpose of this study was to determine by using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) lung scintigraphy whether amifostine given before irradiation protects alveolocapillary integrity in a rabbit model. METHODS AND MATERIALS: Twenty white New Zealand rabbits were randomly divided into 4 groups: (1) control (CONT), (2) amifostine alone (AMF), (3) radiation (RAD), and (4) radiation plus amifostine (RAD+AMF). The AMF and RAD+AMF groups received amifostine. The RAD and RAD+AMF groups were irradiated to the right hemithorax with a single dose of 20 Gy using a (60)Co treatment unit. Amifostine (200 mg/kg) was given i.p. 30 min before irradiation. The (99m)Tc-DTPA radioaerosol study was performed 14 day after irradiation. RESULTS: The mean clearance rate of (99m)Tc-DTPA in control subjects was 140 +/- 21 min. The highest t((1/2)) value was noted in the RAD group (603 +/- 105 min, p = 0.001). There were no significant differences between the (99m)Tc-DTPA lung clearance rates of the CONT, RAD+AMF (238 +/- 24 min), and AMF groups (227 +/- 54 min). The mean penetration index values of CONT, RAD, AMF, and RAD+AMF are 63% +/- 1.6%, 63% +/- 2.5%, 60% +/- 2.9%, and 63% +/- 2%, respectively. CONCLUSIONS: We concluded that amifostine treatment before the lung irradiation protects the lung alveolocapillary integrity. This study confirms the protective effect of amifostine in an acute phase of radiation lung injury.

Value of technetium-99m diethyltriamine pentaaceticacid radioaerosol inhalation lung scintigraphy for the stage of amiodarone-induced pulmonary toxicity.

BACKGROUND: Amiodarone is a potent antiarrhythmic agent that is limited in clinical use by its adverse effects, including potentially life threatening amiodarone-induced pulmonary toxicity (AIPT). The alteration of technetium-99m diethyltriaminepentaaceticacid (Tc-99m DTPA) radioaerosol lung clearance in AIPT was experimentally investigated. METHODS: Eighteen white New Zealand rabbits (initial weight 4.1+/-0.2 kg) were divided into two groups. AIPT group (n=13) was administered amiodarone (20 mg/kg BW) ip as a 5% aqueous solution for 6 week. The controls (n=5) were administered the same amount of 0.9% saline ip. Four rabbits of AIPT group died due to AIPT. The reminders of AIPT group (n=9) and controls underwent Tc-99m DTPA radioaerosol lung scintigraphy at the end of the treatment period. AIPT group was divided into two subgroups according to histopathologic evaluation. AIPT-I had interstitial pneumonitis (n=4) and AIPT-II had interstitial pneumonitis with fibrosis (n=5). RESULTS: The mean T(1/2) values of in control, AIPT-I, and AIPT-II groups were found 54+/-4.4, 39.2+/-11.7 and 114.6+/-16.7 min, respectively. The mean T(1/2) values of Tc-99m DTPA significantly differ than other groups (X(2)=11.78, P=0.02). The significantly increased T(1/2) values was noted in AIPT-II group when compared with control (P=0.001). In contrast, AIPT-I group has significantly lower T(1/2) values than control group (P=0.03). CONCLUSION: We suggested that Tc-99m DTPA radioaerosol inhalation lung scintigraphy provides an accurate evaluation about stage of lung toxicity and therefore may be a useful tool for the monitoring of AIPT.

Increased P wave dispersion: a new finding in patients with syndrome X.

The present clinical study was undertaken in patients with syndrome X, namely angina with normal coronary arteries, to investigate the presence of increased P wave dispersion by comparing patients with coronary artery disease (CAD) and healthy control subjects. Three groups were studied - group A, 21 patients (48 6 years) with syndrome X; group B, 16 patients (56 9 years) with CAD; and group C, 16 healthy subjects (49 8 years). Patients with CAD were older than those in groups A and C (P=0.005 and P=0.035, respectively). All groups demonstrated similar PQ, QRS and RR intervals. Group B had a lower minimum P wave duration than group C (P=0.05). P wave dispersion in group A was found to be higher than that in groups B and C (P=0.018 and P=0.0001, respectively). Patients with syndrome X demonstrated increased P wave dispersion compared to patients with CAD and healthy subjects. High sympathetic tone or autonomic imbalance observed in patients with syndrome X may affect intra-atrial and interatrial conduction times, and leave them prone to develop atrial arrhythmias.

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.