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.

Contrary effects of coenzyme Q10 and vitamin E after testicular ischemia/reperfusion in a rat model validated with glucose metabolism imaging.

OBJECTIVE: To evaluate the efficacy of antioxidants in cellular-level post-ischemia/reperfusion injury of the testis and to validate these effects with 18F-fluorodeoxyglucose positron emission tomography. METHODS: Fifty-six adult male rats were randomly divided into seven groups-Group 1: sham; Group 2: ischemia/reperfusion only group; Group 3: ischemia was induced and vitamin E (100 mg/kg) was administered intraperitoneally 30 min before reperfusion; Group 4: vitamin E was given intraperitoneally without ischemia/reperfusion; Group 5: ischemia was induced and coenzyme Q10 (10 mg/body weight) was administered intraperitoneally 30 min before reperfusion; Group 6: coenzyme Q10 was administered intraperitoneally without ischemia/reperfusion; Group 7: ischemia was induced and coenzyme Q10 + vitamin E was administered intraperitoneally 30 min before reperfusion. After detorsion, fluorodeoxyglucose was applied to all groups according to the animals' weight and fluorodeoxyglucose positron emission tomography was performed after 1 h. In pursuit of imaging, orchiectomy was performed for histopathological and biochemical evaluations. RESULTS: A significant effect of group on catalase, maximum standardized uptake value, and seminiferous tubule diameters (p < 0.005) was observed. According to this, combining ischemia/reperfusion with vitamin E increased the maximum standardized uptake value significantly higher than in all other groups; in addition, catalase was significantly higher than in Groups 4-6. Histopathological outcomes revealed that "sham" had significantly larger seminiferous tubule diameter than Groups 2-4. Also, "ischemia/reperfusion" was the only group which had significantly smaller seminiferous tubule diameters than Groups 6 and 7. CONCLUSION: In contrast to vitamin E, coenzyme Q10 provided remarkable regression of oxidative stress-induced enzymes and revealed consistent effects on histopathological outcomes, which were validated with fluorodeoxyglucose positron emission tomography imaging.

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.

The Clinical Significance of Incidental Parotid Uptake in a PET/CT Study: A Diagnostic Algorithm.

BACKGROUND: Patients diagnosed with cancer do not have sufficient clinical data for the management of incidental parotid lesions. We aimed to reveal the importance of randomized parotid lesions encountered during oncologic F-18 fluorodeoxyglucose positron emission tomography (FDG PET/CT) imaging in our clinical practice and the diagnostic algorithm of such lesions. METHODS: We performed a database search of PET/CT records generated from 2009 to 2015 for "parotid" in reports of patients who underwent PET/CT examination for a known malignancy elsewhere, or cancer screening. RESULTS: Incidental parotid FDG uptake on PET/CT had a prevalence of 1.1%. The incidence of parotid metastasis in our series was 36.4%, and 75% of them had malign melanoma metastasis. Of the 11 cases, 5 were of Warthin tumours, and Warthin tumours showed stronger GLUT1 expression than metastatic parotid lesions. CONCLUSION: In patients with malignancy elsewhere, focal involvement of FDG by the parotid gland, especially if malignant melanoma or SCC is absent, should not be considered a metastatic disease without histopathologic confirmation. If parotid disease would change the patient's treatment plan and disease stage, the parotid lesion should be evaluated by additional methods, such as fine needle aspiration biopsy.

Radioprotective Effects of Amifostine, L-Carnitine and Vitamin E in Preventing Early Salivary Gland Injury due to Radioactive Iodine Treatment.

OBJECTIVE: Standard treatment of differentiated thyroid cancer includes total thyroidectomy and high-dose Radioactive Iodine Therapy (RIT) for ablation of remnant thyroid tissue. When administered systemically, RIT can cause radiation-induced damage in non-targeted normal tissues. The aim of the present study was to compare the protective effects of amifostine (AMI), LCarnitine (LC), and Vitamin E (EVIT) against high dose radioactive iodine treatment induced Salivary Gland (SG) damage using SG scintigraphy and histopathological examination. METHODS: Forty adult guinea pigs were studied. Twenty guinea pigs receive 555-660 MBq 131Iodine intraperitoneally (IP) to ablate the thyroid and impair the parenchymal function of the SGs. The animals were divided into eight groups as follows: (1) Group 1 (control): 1 mL IP PS (physiological saline); (2) Group 2: single dose of 200 mg/kg IP AMI one hour prior to 1 mL IP PS; (3) Group 3: 200 mg/kg IP LC and 1 mL IP PS for 10 days; (4) Group 4: 40 mg/kg intramuscular (IM) EVITand 1 mL IP PS for 10 days; (5) Group 5: IP RIT after premedication; (6) Group 6: Single dose of 200 mg/kg IP AMI one hour prior to RIT and IP RIT after premedication; (7) Group 7: IP RIT after premedication and 200 mg/kg IP LC for 10 days starting one day before RIT; and (8) Group 8: IP RIT after premedication and 40 mg/kg IM EVIT for 10 days starting one day before RIT. Scintigraphy was performed 1 month after treatment. SGs were examined by light microscopy and a histopathological scoring system was used to assess the degree of SG damage. RESULTS: There were significant differences in the body weight and thyroid hormone levels between the groups after treatment. CONCLUSION: The individual use of AMI, LC and EVIT for radioprotection yield different levels of protection against radioactive iodine treatment injury in SGs; however, none of the agents could provide absolute protection at the doses administered in this experimental model.

Biochemical Recurrence of Prostate Cancer Presenting as Solitary Testicular Metastasis on 68Ga-Labeled Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography.

Prostate adenocarcinoma (PCa) is the most frequently diagnosed malignancy in the male population, with the most common sites for secondary lesions being the lymph nodes, bones, and lungs. Testicular metastases from PCa are very rare and mostly identified incidentally after therapeutic orchiectomy for advanced PCa or during autopsy. Here we present a case involving a 64-year-old man with biochemical recurrence of castrated oligometastatic PCa that presented as solitary testicular metastasis on Ga-PSMA ligand positron emission tomography/computed tomography.

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-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings of Pancreatic Hemangiopericytoma.

A 42-year-old woman with a large pancreatic tumor had undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging. Moderate metabolic activity was detected on the head of the pancreas. The tumor was resected and it was histopathologically diagnosed as malign pancreatic hemangiopericytoma (HPC). HPC is a rare soft tissue sarcoma. The tumor is considered aggressive with high rates of local recurrence and metastasis regardless the localization. Herein, we present the imaging characteristics of HPC with 18F-FDG PET/CT.

Liver Metastasis of Lung Cancer Detected with Similar Uptake Pattern on Bone Scintigraphy and Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: What's the Pathophysiologic Mechanism?

Bone scintigraphy with 99mTc diphosphonates may exhibit extraosseous lesions in addition to metastatic lesions. Multiple factors can affect extraosseous 99mTc methylene diphosphonate (MDP) uptake. Similar uptake pattern of 99mTc MDP and fluorine-18 fluorodeoxyglucose (18F FDG) in hepatic metastasis was not already notified. In our case, initial tumor necrosis and subsequent intracellular calcification resulted in similar 99mTc MDP and 18F FDG accumulation in the metastatic area.

Intrathoracic toxic thyroid nodule causing hyperthyroidism with a multinodular normal functional cervical thyroid gland.

Radionuclide scintigraphy with I-131 and Tc-99m pertechnetate ((99)mTc04) has been widely used in detecting toxic nodules. Intrathoracic goiter usually presents as an anterior mediastinal mass. Mostly the connection between intrathoracic mass and the cervical thyroid gland is clearly and easily identified occurring as a result of inferior extension of thyroid tissue in the neck, which is called as secondary intrathoracic goiter. Completely separated, aberrant or in other words primary intrathoracic goiters arise as a result of abnormal embryologic migration of ectopic thyroid closely associated with aortic sac and descend into the mediastinum. Intrathoracic goiters are generally nontoxic nodules existing with mass effect without causing hyperthyroidism. However, mostly reported cases had enlarged thyroid glands in the neck. This report demonstrates the usefulness of I-131 and (99)mTc04 scintigraphy for detecting intrathoracic goiter causing hyperthyroidism with a normal functioned cervical thyroid gland.

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.

The alteration of asymmetric dimetilarginine (ADMA) levels in cardiac and gastrocnemius muscles following radioactive iodine application in guinea pigs and the effect of L-carnitine on this alteration.

PURPOSE: Tissue levels of asymmetric dimetilarginine (ADMA) and symmetric dimetilarginine (SDMA) were investigated in cardiac ventricle and gastrocnemius muscles of guinea pigs treated with radioactive iodine (RAI) alone or in combination with L-carnitine (LC). MATERIAL AND METHODS: Group 1 received no treatment (control group). Group 2 received a total dose of 30 mCi⁻¹kg⁻¹ body weight iodine-131 alone. Group 3 received 200 mg⁻¹kg⁻¹ of LC for 10 days alone. Group 4 received 200 mg⁻¹kg⁻¹ of LC plus RAI therapy. Free thyroid hormones, ADMA and SDMA concentrations were measured. RESULTS: Serum free thyroid hormone concentrations were found decreased in the RAI and LC-RAI groups after RAI application. A significant decrease in ADMA and SDMA concentration was observed in ventricle muscle following RAI application. The LC-RAI group had significantly decreased ADMA levels in ventricle muscle compared with those of the control group. Similarly, SDMA concentrations in ventricle and gastrocnemius muscles of the LC-RAI groups were significantly lower than those of the control groups. CONCLUSIONS: Our results indicated that RAI appears to exert an inhibitory effect on ADMA and SDMA levels of ventricular muscle. LC administration when given adjuvant to RAI therapy may cause a marked decrease in ADMA concentrations of both ventricular and gastrocnemius muscles.

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.