Evaluation of blood supply and metabolism in tumor, axillary lymph node and normal breast tissue with F-18 FDG PET/CT in breast cancer: comparison with pathological prognostic factors.

BACKGROUND AND PURPOSE: Perfusion parameters obtained in F-18 FDG PET/CT performed for staging purposes in breast cancers may provide additional information about tumor biology as well as glucose metabolism. The aim of this study was to evaluate throughout F-18 FDG PET/CT the relationship between blood flow and glucose metabolism and histological parameters of the primary tumor, normal mammary gland, and axillary lymph nodes in breast cancer patients. MATERIALS AND METHODS: Sixty six female patients (mean age 51 y ± 12,81) were prospectively included to this study. We performed dynamic blood flow (f) study that started with 296-444 MBq (8-12 mCi) F-18 FDG injection and lasted for 10 minutes, and glucose metabolism (m) imaging one hour later. On each frame, mean activity concentration (AC) values (Bq/mL) were recorded on a spherical volume of interest (VOI) having a volume of ~ 1 cm3 on the hottest voxel of primary tumor (T), across normal breast gland (NG) and ipsilaterally axillary lymph nodes (iLN). Correlations among PET parameters and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (c-erbB2) and Ki67 index were analyzed. RESULTS: T volume (TV) ranged from 1.1 to 85.28 cm3 [median (IR): 6.44 (11.78)]. There were positive correlations between c-erbB2 and TACf and between c-erbB2 and iLNACf (p = 0.045, r = + 0.248; p = 0.050, r = + 0.242). In the ER positive (ERP) patients, TV and TACm were significantly lower than those of ER negative (ERN) (respectively p = 0.044 and p = 0.041). In patients with two positive Ki-67 indices, iLN-SUVmax was significantly higher than one-positive patients (p = 0.020). There was a negative correlation between NGACm and histological grade of tumor (p = 0.005, r = - 0.365). CONCLUSIONS: Breast cancer shows differences in progression, metastasis and survival due to its diversity in terms of molecular, biological and angiogenesis. High glucose metabolism in breast cancers is associated with tumor aggressiveness. Being able to examine tumor tissue characteristics such as blood flow and glucose metabolism with a single diagnostic technique and to reveal its relationship with histological parameters can provide a reliable pretherapeutic evaluation in breast cancers.

DTPA clearance test: a sensitive method for detecting radiation-induced lung fibrosis in lung cancer patients.

OBJECTIVE: The aim of this study is to analyze the frequency of lung injury and the sensitivity of the diethylenetriamine penta-acetic acid (DTPA) clearance test in detecting lung injury in patients undergoing radiotherapy (RT) to the thorax. MATERIAL AND METHOD: Twenty individuals scheduled for RT for lung cancer were included as the patient group. The healthy control group consisted of 20 age and gender-matched individuals who were nonsmokers with no history of comorbidities. We conducted follow-up with patients at 0-1-6 months, performing carbon monoxide diffusion test (DLCO), DTPA clearance test (excluding the first month), and high-resolution computed tomography of the thorax. The control group was followed up with DLCO between the baseline and 6th months. RESULTS: Ninety percent of the patient group was male, and the median age was 62 years. Seventy percent of the patients had squamous cell carcinoma and adenocarcinoma. Pneumonitis was detected in the patient group in the first month (100%) and fibrosis in the sixth month (%100) Both at the beginning and in the sixth month, the DLCO values of patients who received RT were lower than those of the control group ( P  = 0.001 and P  < 0.001, respectively). While DTPA clearance was similar between irradiated and non-radiated lungs at the beginning, there was a substantial decrease in the irradiated lung in the sixth month( P  = 0.001). There was no significant correlation between malignancy type, RT dose, and tumor size( P  > 0.05). CONCLUSION: The DTPA clearance test could be an alternative method for demonstrating radiation injury in patients receiving RT.

Could the skewness and kurtosis texture parameters of lesions obtained from pretreatment Ga-68 DOTA-TATE PET/CT images predict receptor radionuclide therapy response in patients with gastroenteropancreatic neuroendocrine tumors?

PURPOSE: In our study, tumor heterogeneity was evaluated using the parameters skewness and kurtosis on pretreatment Ga-68 DOTA-TATE PET/CT to assess therapy responses of lesions in patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs) treated with peptide receptor radionuclide therapy (PRRT). METHOD: We retrospectively studied the texture analysis with relatively simple first-order parameters skewness and kurtosis on pretreatment Ga-68 DOTA-TATE PET/CT from 22 patients (eight females, 14 males; with a mean age: 54 ± 11 years) with GEP NETs who were treated with 2-6 therapy cycles of Lu-177 DOTA-TATE. A total of 326 lesions of 22 patients were evaluated in terms of treatment response by Ga-68 DOTA-TATE PET/CT examination performed before and after treatment. Receiver-operating characteristic (ROC) curves were generated to assess skewness and kurtosis to discriminate between responder and nonresponder lesions. RESULT: A total of 326 lesions of 22 patients were evaluated and 137 lesions responded partially or completely to the treatment, 189 lesions did not respond to treatment, remained stable or progressed. The skewness and kurtosis values of the lesions which did not respond to the PRRT were significantly higher than those with response to PRRT treatment (P < 0.001 and P = 0.004, respectively). However, ROC curves provided a moderate area under the curve value for skewness and a relatively low value for kurtosis (0.619 and 0.518, respectively). CONCLUSION: Texture analysis using skewness and kurtosis of the lesions on pretreatment Ga-68 DOTA-TATE PET/CT was able to predict their responsiveness to PRRT.

Quantitative comparison of low dose and standard dose radioiodine therapy effectiveness in patients with low risk differentiated thyroid cancer.

BACKGROUND: The aim of this paper was to compare the results of postoperative I-131 remnant ablation therapy using a quantitative data in the low activity (1110 MBq) and standard dose (3700 MBq). METHODS: The study included two groups of patients with low risk differentiated thyroid cancer (DTC): Group L (low dose group) included 54 patients who were treated with 1110 MBq I-131 and Group S (standard dose group) included 61 patients treated with 3700 MBq. The postoperative thyroid remnants were assessed with the pretreatment thyroid uptake test (PTUT) and the whole body scans (WBS) were performed in the 7th day after the ablation treatment. We obtained the average count per pixel from the standard region of interest analysis of the thyroid bed (Tavc), liver (Lavc), thigh (Thavc) and whole body (WBkc). At the sixth month after the treatment, WBS were performed to 106 patients (45 patients from Group L and 61 patients from Group S) to evaluate the success of ablation treatment. RESULTS: A significant difference in PTUT and Tavc was not found between the two groups (P>0.05). However, Lavc, Thavc and WBkc were significantly higher in Group S compared with Group L (P<0.001). Although the percentage of ablation was higher in Group S (49 of 61 patients, 80.3% versus 34 of 45 patients, 75.6%), the statistical difference was not significant (P>0.05). CONCLUSIONS: In low risk DTC patients, low dose radioactive iodine can ablate thyroid remnants as effectively as a higher dose with less radiation exposure to other non-target organs and the whole body.

Combined imaging with 68Ga-DOTA-TATE and 18F-FDG PET/CT on the basis of volumetric parameters in neuroendocrine tumors.

AIM: To assess the additional contribution of the combined imaging approach with Ga-DOTA-TATE and fluorine-18 fluorodeoxyglucose (F-FDG) on the basis of volumetric parameters in neuroendocrine tumors (NETs). MATERIALS AND METHODS: Forty-one patients with NET (19 women, 22 men; age range: 30-79 years; mean age: 56.7±12.3 years) underwent Ga DOTA-TATE and F-FDG PET/computed tomography (CT) imaging. Within the drawn regions of interest, in addition to evaluating the maximum and mean standardized uptake values (SUVmax and SUVmean), the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in F-FDG PET/CT imaging, and the somatostatin receptor density and total lesion somatostatin receptor expression (TLSRE) in Ga somatostatin receptor imaging (SRI) were measured. The patients were graded on the basis of the proliferation index: well (G1; Ki-67 ≤2), moderately (G2; Ki-67=3-20), and poorly (G3; Ki-67>20) differentiated groups. RESULTS: Of the 41 NET patients, 22, 14, and five were in the G1 (53.7%), G2 (34.1%), and G3 (12.2%) groups, respectively. Liver metastases had significantly higher TLSRE values than the TLG values. Ki-67 levels showed a positive correlation with the primary tumor MTV and TLG values. Cg-A levels had a positive correlation with the volumetric parameters of the whole-body tumor burden (P<0.001). CONCLUSION: Ga SRI and F-FDG PET/CT provide complementary information on treatment protocol and response assessment. While assessing the prognosis and tumor aggressiveness, lesions and whole-body tumor burdens can be calculated on the basis of volumetric parameters by F-FDG PET/CT using MTV and TLG, and by Ga SRI using somatostatin receptor density and TLSRE.

PET/CT and Bremsstrahlung Imaging After 90Y DOTANOC Therapy for Rectal Net With Liver Metastases.

Peptide receptor radionuclide therapy with Lu or Y is promising with successful results in somatostatin receptor-positive tumors. In all radiation therapies, knowledge of the radiation dose received by the target, and other organs in the body is essential to evaluate the risks and benefits of any procedure. We report a case of liver metastases from a rectal neuroendocrine tumor, which was treated with Y DOTANOC. Posttreatment whole-body planar images were acquired through Bremsstrahlung radiations of Y on a γ-camera, and thoracolumbar PET/CT images were acquired on PET.

Imaging of primary liver carcinosarcoma scintigraphically; a case report.

UNLABELLED: Primary liver carcinosarcoma is a very rare disease. There have been only a few cases described to date, none of which has been imaged by bone scintigraphy. A 69-year-old man who developed right back pain and weight loss was admitted to our hospital. Tenderness of the right upper abdomen, hepatomegaly, and a giant mass were the main physical examination signs. Abdominal ultrasonography showed a large lobulated heterogeneous echogenic solid mass with multiple cystic areas of varying size and a highly echogenic region that had posterior acoustic shadowing within the mass in the right lobe of the liver. Labeled erythrocyte imaging and (99m)Tc-nanocolloid liver-spleen scan were performed to exclude hemangioma, showing a large intrahepatic photon deficient area. (99m)Tc-methylene diphosphonate (MDP) bone scintigraphy revealed heterogeneous, irregular and dense activity accumulation thought to be osteoblastic activity in the liver mass. Postsurgical pathological diagnosis revealed "carcinosarcoma". CONFLICT OF INTEREST: None declared.

The value of Tc-99m tetrofosmin scintimammography in the assessment of P-glycoprotein in patients with breast cancer.

P-glycoprotein (Pgp) overexpression has been shown to be correlated with resistance to chemotherapy in patients with malignant breast tumors. The aim of our study was to investigate the role of technetium-99m-tetrofosmin (99mTc-TF) as a functional imaging agent reflecting Pgp expression in these tumors. We prospectively studied 28 patients (26 females, 2 males; mean age, 53.07±9.88 years; range, 38 to 70 years) with breast cancer to ascertain the relationship between the degree of accumulation (lesion/nonlesion=L/NL) and percentage washout (WO%) rate of 99mTc-TF and expression of Pgp in tumor tissues. All patients received 555-740 MBq of 99mTc-TF intravenously at the arm controlateral to the suffering breast. Planar images were obtained 10 and 120 min post injection from prone lateral and anterior views with an acquisition time of 5 min. Visual and semiquantitative measurements were performed. The L/NL ratios and WO% rates were calculated semiquantitatively. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1. The L/NL ratios and WO% rates were related with the level of Pgp determined immunohistochemically. Our results showed an inverse correlation between the L/NL ratios of 99mTc-TF and the density of Pgp expression in tumor tissues, whereas there was no appreciable correlation between the tumor WO% rates of 99mTc-TF and the level of Pgp expression (P=0.275). The values for the L/NL ratios were significantly lower for those tumors expressing Pgp at high levels than those with intermediate or no Pgp expression (P<0.002 and P<0.04). In conclusion, although our results warrant further studies, our data strongly suggest that 99mTc-TF imaging is useful to noninvasively determine the presence of multidrug resistance in patients with breast cancer.

Octreotide uptake in parathyroid adenoma.

The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared.

Is Every Patient Followed up as a Papillary Thyroid Cancer Patient Really That?

UNLABELLED: We report the case of a 64-year-old man followed up for two years as suffering from differentiated thyroid cancer (DTC). In the patient's follow up, despite thyroglobulin level and I-131 whole body scan results being normal, metastases were identified at the 4th thoracic vertebra corpus by MR. Histopathological findings were carcinoma metastases. F-18 FDG PET/CT showed increased metabolic activity in the right renal mass, bilaterally in the surrenal gland, multiple lymph nodes in the thoracic and abdominal para-aortic region and in multiple vertebral and pelvic bones. An excisional biopsy of the right renal mass was reported as renal cell carcinoma. Immunohistochemical staining performed retrospectively to the first thyroid preparation showed renal cell carcinoma metastases. Consequently, any patient who presents with a thyroid nodule can also be considered as possibly suffering from metastatic disease. F-18 FDG PET/CT can provide valuable information in finding the primary focus and metastases. CONFLICT OF INTEREST: None declared.

Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of fibrosis in chronic hepatitis: histopathological correlation.

PURPOSE: Although liver biopsy remains the gold standard in the staging of liver fibrosis in chronic hepatitis C virus (HCV) infection, several noninvasive methods are under evaluation for clinical use. The aim of this study was to evaluate the utility of hepatobiliary function through technetium-99m-N-(-3-bromo-2,4,6-trimethylacetanilide) iminodiacetic acid (Tc-mebrofenin) scintigraphy in evaluating liver fibrosis in patients with chronic HCV infection. METHODS: We studied 62 patients with HCV (18 men, 44 women). The patients were allocated into three groups according to histopathological score: group 1: portal/periportal fibrosis (21 patients; eight men, 13 women); group 2: bridging fibrosis (23 patients; seven men, 16 women); and group 3: incomplete/complete cirrhosis (18 patients; three men, 15 women). As a control group, 20 healthy volunteers (six men and 14 women) were studied. Hepatocyte mebrofenin uptake rate, the time required for maximal hepatic activity (Tmax), and the time required for peak activity to decrease by 50% (T1/2max) were calculated using Tc-mebrofenin cholescintigraphy. Scintigraphic parameters were correlated with biochemical parameters and liver histopathology. RESULTS: The uptake rates were significantly decreased in all groups with fibrosis compared with the controls (P<0.05). The correlation between the severity of fibrosis and Tc-mebrofenin uptake rate was strongly significant (r=-0.81, P<0.0001). Tmax and T1/2max were significantly prolonged in groups 2 and 3 compared with the controls. Histopathology score was correlated moderately with Tmax and T1/2max (r=0.61, P<0.0001 and r=0.52, P<0.0001, respectively). CONCLUSION: The assessment of hepatobiliary function by Tc-mebrofenin scintigraphy may be a good choice for assessing the severity of liver fibrosis in patients with HCV.

Effect of nasal packing and haemostatic septal suture on mucociliary activity after septoplasty: an assessment by rhinoscintigraphy.

Nasal packing may influence the mucociliary clearance of the nose in the postoperative healing phase. In an attempt to overcome some of this problem, a haemostatic septal suturing technique was conceived. In this prospective study, we aimed to investigate the effects of nasal packing and septal suturing technique on mucociliary clearance by rhinoscintigraphy. Forty-eight adult patients who had undergone septoplasty were included in the investigation. Preoperatively, the patients were allocated into three groups: group 1, fingerstall packs filled with gauze and smeared with vaseline were used (11 male, 4 female); group 2, silicon septal splint packs were used (11 male, 4 female); group 3, haemostatic septal sutures were used (14 male, 4 female). Mucociliary clearance was measured by rhinoscintigraphy in all patients before surgery and 6 weeks after surgery. The nasal mucociliary clearance was presented as the velocity (mm/min) of nasal mucociliary transport of the (99m)Tc-MAA droplet. The mean velocity of nasal mucociliary clearances before and after surgery for group 1, group 2 and group 3 were 1.85 +/- 0.67 versus 2.43 +/- 0.78 mm/min, 2.36 +/- 0.80 versus 2.92 +/- 0.96 mm/min and 2.03 +/- 0.58 versus 2.62 +/- 0.65 mm/min, respectively. A significant difference in nasal mucociliary clearance was observed after surgery in all groups (p < 0.001). No significant differences were found between the groups regarding mucociliary clearance before and after surgery. Patients with septal deviation have a prolonged mucociliary transit time as compared with postoperative. Nasal packing did not significantly influence the mucociliary clearance in the postoperative healing phase.

Correlation of elevated leptin levels in amniotic fluid and maternal serum in neural tube defects.

OBJECTIVE: To measure maternal serum and amniotic fluid leptin concentrations in pregnant women diagnosed antenatally as having fetuses with a neural tube defect in the second trimester. METHODS: Twenty pregnant women who had fetuses with a neural tube defect detected on ultrasonography (neural tube defect group) in the second trimester and 20 women who had abnormal triple screens indicating an increased risk for Down syndrome but had healthy fetuses (control group) were enrolled in the study. Amniotic fluid was obtained by amniocentesis, and maternal serum samples were taken simultaneously. RESULTS: The mean leptin levels in amniotic fluid (P <.001) and maternal serum (P <.05) of patients who had fetuses with a neural tube defect were found to be significantly higher than control group levels. The mean leptin levels in maternal serum of both groups were also higher than leptin levels in amniotic fluid (P <.05 for the neural tube defect group and P <.001 for the control group). Although there were significant correlations between maternal weight, weight gain, body mass index at the time of amniocentesis, and maternal serum leptin concentrations in both groups, a significant correlation between leptin concentrations in maternal serum and amniotic fluid was found only in the neural tube defect group (P <.05). CONCLUSIONS: We found significantly higher leptin levels in both amniotic fluid and maternal serum of patients who had fetuses with a neural tube defect. We suggest that the main source of leptin in amniotic fluid of pregnant women who had fetuses with a neural tube defect is the leakage into amniotic fluid from cerebrospinal fluid. The increase of maternal serum leptin concentrations has been attributed to the transportation of amniotic fluid leptin to the maternal circulation.

A comparison between the effects of low dose (1 microg) and standard dose (250 microg) ACTH stimulation tests on adrenal P450c17alpha enzyme activity in women with polycystic ovary syndrome.

OBJECTIVE: Numerous studies have found elevated androgen production by the adrenal glands in patients with polycystic ovary syndrome (PCOS). However, the role and the mechanisms responsible for the adrenal androgen excess in women with PCOS are not well understood. DESIGN: Our aim was to compare 17-hydroxyprogesterone (17-OHP), androstenedione, dehydroepiandrosterone sulfate (DHEAS) and cortisol responses to a low dose (1 microg) ACTH stimulation test (LDT) with the responses to a standard dose (250 microg) ACTH stimulation test (SDT) in patients with PCOS. METHODS: Fifty women with PCOS (mean age 25.4+/-0.7 years) and 20 healthy women (mean age 27.3+/-2.2 years) were included in the study. The patients and controls underwent ACTH stimulation tests with 1 microg and 250 microg synthetic ACTH in the follicular phase of their cycles. Venous blood was drawn at 0, 30 and 60 min for determination of serum cortisol, 17-OHP, androstenedione and DHEAS levels. RESULTS: In PCOS subjects, peak and area under the curve (AUC) 17-OHP (9.3+/-0.3 nmol/l, 378.4+/-61 nmol/lx60 min), androstenedione (15.6+/-0.6 nmol/l, 806.4+/-52 nmol/lx60 min) and DHEAS (7.5+/-0.4 micromol/l, 385.6+/-25.5 micromol/lx60 min) responses to SDT were significantly higher than the levels in healthy women (respectively 5.7+/-0.3 nmol/l and 249.4+/-52.2 nmol/lx60 min for 17-OHP; 9.1+/-0.3 nmol/l and 413.7+/-31.6 nmol/lx60 min for androstenedione; 4.3+/-0.4 micromol/l and 224.9+/-24.5 micromol/lx60 min for DHEAS) (P<0.05). Peak and AUC cortisol responses to SDT were similar in PCOS and control subjects. Peak and AUC cortisol and 17-OHP responses to LDT in women with PCOS were similar to the values obtained in healthy women. Peak androstenedione (12.5+/-0.6 nmol/l) and peak (6.5+/-0.5 nmol/l) and AUC (336.3+/-22.4 micromol/lx60 min) DHEAS responses to LDT were significantly higher in women with PCOS. CONCLUSIONS: These results show that LDT is capable of revealing the adrenal hyperactivity in women with PCOS. Adrenal P450c17alpha enzyme dysregulation in PCOS is revealed by ACTH stimulation at a pharmacological dose (250 microg) but not by a physiological dose (1 microg). LDT is able to demonstrate adrenal hyperactivity characterized by an increase in DHEAS levels.