Hypoxia imaging predicts success of hypoxia-induced cytosine deaminase/5-fluorocytosine gene therapy in a murine lung tumor model.

Tc-99m-HL91 is a hypoxia imaging biomarker. The aim of this study was to investigate the value of Tc-99m-HL91 imaging for hypoxia-induced cytosine deaminase (CD)/5-fluorocytosine (5-FC) gene therapy in a murine lung tumor model. C57BL/6 mice were implanted with Lewis lung carcinoma cells transduced with the hypoxia-inducible promoter-driven CD gene (LL2/CD) or luciferase gene (LL2/Luc) serving as the control. When tumor volumes reached 100 mm(3), pretreatment images were acquired after injection of Tc-99m-HL91. The mice were divided into low and high hypoxic groups based on the tumor-to-non-tumor ratio of Tc-99m-HL91. They were injected daily with 5-FC (500 mg kg(-1)) or the vehicle for 1 week. When tumor volumes reached 1000 mm(3), autoradiography and histological examinations were performed. Treatment with 5-FC delayed tumor growth and enhanced the survival of mice bearing high hypoxic LL2/CD tumors. The therapeutic effect of hypoxia-induced CD/5-FC gene therapy was more pronounced in high hypoxic tumors than in low hypoxic tumors. This study provides the first evidence that Tc-99m-HL91 can serve as an imaging biomarker for predicting the treatment responses of hypoxia-regulated CD/5-FC gene therapy in animal tumor models. Our results suggest that hypoxia imaging using Tc-99m-HL91 has the predictive value for the success of hypoxia-directed treatment regimens.

The use of dual-phase 18F-FDG PET in characterizing thyroid incidentalomas.

AIM: To examine the usefulness of dual-phase 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) for the evaluation of thyroid incidentalomas. MATERIALS AND METHODS: In this retrospective study, cases with focal thyroid lesions seen incidentally at FDG PET in which the histopathological diagnosis was available and in which dual-phase FDG PET imaging was performed at 1 and 2 h after FDG injection were reviewed. In the included cases, the 1 and 2 h maximal standard uptake value (1-hour maximal SUV and 2-hour maximal SUV, respectively) and retention index (RI) were calculated, and the differences between benign and malignant thyroid incidentalomas were analysed. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of 1-hour maximal SUV, 2-hour maximal SUV, and RI to discriminate benign from malignant lesions. RESULTS: A total of 39 patients (25 females, 14 males) with 45 lesions (17 malignant, 28 benign) were included. In malignant thyroid incidentalomas, the average 1-hour maximal SUV, 2-hour maximal SUV, and RI were 5.20, 5.72, and 7.67%, respectively, and in benign thyroid incidentalomas the values were 4.67, 4.97, and 7.38%, respectively. There were no significant differences in 1-hour maximal SUV, 2-hour maximal SUV, and RI between benign and malignant lesions. The area under the ROC curve did not differ from 0.5. CONCLUSION: Dual-phase FDG PET is not useful for differentiating benign from malignant thyroid incidentalomas.

A retrospective study of pulmonary infarction in patients with systemic lupus erythematosus from southern Taiwan.

Since large-scale reports of pulmonary infarction in systemic lupus erythematosus (SLE) are limited, a retrospective study was performed for this manifestation in 773 hospitalized patients in southern Taiwan from 1999 to 2009. Pulmonary infarction was defined as the presence of pulmonary embolism, persistent pulmonary infiltrates, and characteristic clinical symptoms. Demographic, clinical, laboratory, and radiological images data were analyzed. There were 12 patients with pulmonary embolism and 9 of them had antiphospholipid syndrome (APS). Six patients (19 to 53 years, average 38.2 ± 12.6) with 9 episodes of lung infarction were identified. All cases were APS and four episodes had coincidental venous thromboembolism. There were four episodes of bilateral infarction and seven episodes of larger central pulmonary artery embolism. Heparin therapy was routinely prescribed and thrombolytic agents were added in two episodes. Successful recovery was noted in all patients. In conclusion, there was a 0.8% incidence of pulmonary infarction in patients with SLE, all with the risk factor of APS. Differentiation between pulmonary infarction and pneumonia in lupus patients should be made; they have similar chest radiography with lung consolidation but require a different clinical approach in management. Although this report is a retrospective study with relatively small numbers of lupus patients with lung infarcts, our observation might provide beneficial information on the clinical features and radiological presentations during the disease evolution of pulmonary infarction in SLE with APS.

Characterization of a serine protease-mediated cell death program activated in human leukemia cells.

Tightly controlled proteolysis is a defining feature of apoptosis and caspases are critical in this regard. Significant roles for non-caspase proteases in cell death have been highlighted. Staurosporine causes a rapid induction of apoptosis in virtually all mammalian cell types. Numerous studies demonstrate that staurosporine can activate cell death under caspase-inhibiting circumstances. The aim of this study was to investigate the proteolytic mechanisms responsible for cell death under these conditions. To that end, we show that inhibitors of serine proteases can delay cell death in one such system. Furthermore, through profiling of proteolytic activation, we demonstrate, for the first time, that staurosporine activates a chymotrypsin-like serine protease-dependent cell death in HL-60 cells independently, but in parallel with the caspase controlled systems. Features of the serine protease-mediated system include cell shrinkage and apoptotic morphology, regulation of caspase-3, altered nuclear morphology, generation of an endonuclease and DNA degradation. We also demonstrate a staurosporine-induced activation of a putative 16 kDa chymotrypsin-like protein during apoptosis.

Clinical significance and outcome of one or two rib lesions on bone scans in breast cancer patients without known metastases.

The presence of one or two rib lesions on bone scans of post-treatment breast cancer patients without known metastases often makes clinical decision making problematic. The aim of this study was to identify skeletal metastasis predictors that might help the management of these patients. We recruited post-treatment breast cancer patients without overt metastases whose bone scans showed (1) one or two rib hot spots, or (2) one rib lesion and a concurrent bone abnormality. Their clinical and serial scintigraphic data were collected, reviewed and evaluated for correlations. After their first abnormal bone scans, 23 patients (11 of the 77 patients initially with one rib lesion (incidence, 14.3%), three of the 27 patients with two rib lesions (incidence, 11.1%), and nine of the 11 patients with one rib lesion plus a concurrent bone abnormality (incidence, 81.8%)) developed multiple bone metastases within 2 years of the initial rib lesions in all but one case. Univariate analyses revealed that a concurrent bone lesion other than the rib, direct tumour invasion to the chest wall or skin, and 10 or more lymph nodes involved were associated with increased risks of bone metastases whereas longer persistence of the rib lesions was associated with a lower risk. Multivariate proportional hazard analyses indicated that patients with a concurrent bone lesion other than the rib (relative risk (RR)=39.65; 95% confidence interval (CI)=8.13-193.28), 10 or more lymph nodes involved (RR=13.49; 95% CI=2.09-86.91), and no radiotherapy (RR=7.59; 95% CI=2.11-27.39) were more likely to have bone metastases, while those with longer persistence of the rib lesions (RR=0.92; 95% CI=0.84-0.98) and longer time interval between surgery and the rib lesion detection (RR=0.96; 95% CI=0.94-0.99) were less likely. We have identified clinical features applicable to risk stratification. High incidence of bone metastases was noted in patients with one rib lesion and a concurrent bone abnormality. Regular follow-up for 2 years after detection of rib lesions is recommended, especially for those with risk factors.

Evolution of differential renal function after acute pyelonephritis.

(99m)Tc dimercaptosuccinic acid (DMSA) renal scans can provide accurate diagnosis of acute pyelonephritis, its sequelae (renal scars) and differential renal function (DRF). The purposes of this retrospective study were (1) to assess the relationship between DRF obtained during acute pyelonephritis and at follow-up, and (2) to elucidate the value of initial DRF in predicting subsequent renal scars. A total of 47 children were enrolled. All had both unilateral acute pyelonephritis diagnosed by initial DMSA renal scans, and follow-up DMSA renal scans. We found the correlation between initial and follow-up DRF poor (adjusted R2 = 0.396). Whether or not renal scars developed determined the follow-up DRF. Vesicoureteral reflux was significantly more common in children who developed renal scars. In addition, the higher the grade of vesicoureteral reflux, the lower the follow-up DRF and the improvement in DRF. When using a DRF of 46% as the cut-off value to predict subsequent renal scars, the sensitivity and specificity were 47.8% and 83.3%, respectively. Owing to the low sensitivity, initial DRF is not suitable for predicting the occurrence of renal scars.

Renal fibrosis: prediction from acute pyelonephritis focus volume measured at 99mTc dimercaptosuccinic acid SPECT.

PURPOSE: To evaluate whether acute pyelonephritis lesion volume derived from acute technetium 99m ((99m)Tc) dimercaptosuccinic acid (DMSA) renal single photon emission computed tomographic (SPECT) images is predictive of the development of subsequent renal fibrosis. MATERIALS AND METHODS: Children with acute pyelonephritis underwent (99m)Tc DMSA renal SPECT during acute infection and 6-10 months later. At quantitative analysis, the volume of photopenic lesions and the ratio of radioactivity in the photopenic lesion to that in normal renal tissue were calculated. Sensitivity, specificity, and positive and negative predictive values were determined. RESULTS: Sixty-nine acute pyelonephritis foci in 44 children were analyzed. Thirty-seven (54%) of these lesions were normal on follow-up renal scans, while 32 (46%) developed scars. Significant differences in the photopenic lesion volume were found between the two groups (P < .001). When photopenic lesion volume indicated a positive diagnosis (>or=4.6-cm(3) lesion volume), sensitivity, specificity, positive predictive, and negative predictive values were 96.7%, 92.3%, 90.6%, and 97.3%, respectively. CONCLUSION: Quantitative analysis of acute DMSA renal SPECT findings is valuable in predicting renal fibrosis. The volume of an acute pyelonephritis lesion is useful in predicting the development of fibrosis.

Alzheimer's disease: scintigraphic appearance of Tc-99m HMPAO brain spect.

UNLABELLED: To investigate the value of Tc-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) single photon emission computed tomography (SPECT) as a diagnostic test for Alzheimer's disease. METHODS AND PATIENTS: Tc-99m HMPAO SPECT was performed on 140 patients and 20 controls. A final diagnosis was established for 115 patients, 58 of whom had Alzheimer's disease. The probability of AD was determined for seven scintigraphic patterns. The probability of Alzheimer's disease was 14% for patients with memory loss and normal perfusion. For patients with abnormal perfusion patterns, the probability of Alzheimer's disease was 87% with bilateral temporoparietal defects, 73% with bilateral temporoparietal defects plus additional defects, 62% with a unilateral temporoparietal defect, 33% with a frontal defect only, 0% with other large defects, and 0% with multiple small cortical defects. In 115 patients with the complaint of memory loss or cognitive abnormalities, bilateral temporoparietal hypoperfusion with or without additional hypoperfusion was more frequent than other scintigraphic patterns in patients with Alzheimer's disease. Tc-99m HMPAO SPECT offers the clinician the possibility of differentiating dementias on the basis of differences in perfusion patterns.

Use of 99mTc (V) DMSA scintigraphy in the detection and localization of intestinal inflammation: comparison of findings and colonoscopy and biopsy.

PURPOSE: To evaluate the potential use of technetium 99m (99mTc) (V) dimercaptosuccinic acid (DMSA) scintigraphy in the detection and localization of intestinal inflammation. MATERIALS AND METHODS: In a prospective study, 62 patients who were suspected of having intestinal inflammation and 30 control subjects were enrolled. All patients underwent 99mTc (V) DMSA scintigraphy and colonoscopy with biopsy within 1 week. 99mTc (V) DMSA scintigrams were interpreted blindly with respect to clinical information, and radiotracer uptake in the bowel segments was graded. The findings were then compared with the results of the colonoscopy and colonoscopic biopsy. RESULTS: In the detection of intestinal inflammation, findings at 99mTc (V) DMSA scintigraphy were as follows: true-positive in 55, false-positive in two, true-negative in 32, and false-negative in three. Overall sensitivity was 95%; overall specificity, 94%; and overall accuracy, 95%. CONCLUSION: Our results show that 99mTc (V) DMSA scintigraphy is a useful noninvasive diagnostic test for the detection and localization of intestinal inflammation.

Heroin-induced rhabdomyolysis as a cause of reflex sympathetic dystrophy.

Reflex sympathetic dystrophy is an excessive or abnormal response of the sympathetic nervous system in an extremity to an injury or other condition. The authors describe a 37-year-old man who experienced constant pain and vasomotor instability in both feet after nontraumatic rhabdomyolysis secondary to smoking heroin. Three-phase bone scintigraphy was performed and revealed significantly increased blood-flow, blood-pool, and delayed-phase radioactivity. The follow-up three-phase bone scinitigram showed less radiotracer uptake that was consistent with a good response to calcitonin therapy. Heroin-induced rhabdomyolysis should be added to the list of precipitating conditions that can induce this syndrome.

Differences in 99mTc-HMPAO brain SPET perfusion imaging between Tourette's syndrome and chronic tic disorder in children.

Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because both the outcome and the treatment of these two childhood-onset diseases are distinct. We assessed the sensitivity and specificity of brain single-photon emission tomography (SPET) perfusion imaging in distinguishing the two diseases, and characterized their different cerebral perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual interpretation and semiquantitative analysis of SPET images were performed. On visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had lesions characterized by decreased perfusion. The left hemisphere was more frequently involved. None of the children with chronic tic disorder had a visible abnormality. Semi-quantitative analysis showed that, compared with children with chronic tic disorder, children with Tourette's syndrome had significantly lower perfusion in the left lateral temporal area and asymmetric perfusion in the dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the visual approach, brain SPET perfusion imaging is sensitive and specific in differentiating Tourette's syndrome and chronic tic disorder. The perfusion difference between the two groups, demonstrated by semi-quantitative analysis, may be related more to the co-morbidity in Tourette's syndrome than to tics per se.

Protein-losing enteropathy: diagnosis with (99m)Tc-labeled human serum albumin scintigraphy.

PURPOSE: To investigate the diagnostic value of technetium 99m-labeled human serum albumin (HSA) scintigraphy in a group of patients suspected of having protein-losing enteropathy (PLE). MATERIALS AND METHODS: After intravenous injection of 740 MBq of freshly prepared (99m)Tc HSA, serial images of the abdomen were obtained from 10 minutes until 24 hours after injection. A (99m)Tc HSA scan was considered positive for PLE if there was visible tracer exudation in the gut. The diagnosis was established on the basis of standard clinical and biopsy findings. RESULTS: Thirty-nine scans were obtained: 27 scans in 26 suspected cases of PLE and 12 scans in control subjects with no known gastrointestinal disease. Twenty-five of the 26 studies in patients suspected of having PLE showed (99m)Tc HSA activity in the bowel. Among the 25 studies with positive findings, seven demonstrated PLE only on images obtained 24 hours after injection. In the control subjects, no activity was seen in the bowel. CONCLUSION: (99m)Tc HSA with serial scanning for up to 24 hours is reliable and useful for imaging PLE. Sites of protein loss may also be demonstrated. This imaging method is convenient, easy to perform, and yields results within 24 hours.

Bilateral orbital pseudotumor with suprasellar and pulmonary involvement: report of a case.

A 39-year-old man had bilateral proptosis and blurred vision for I week. Computed tomography and magnetic resonance imaging showed signs of bilateral orbital pseudotumor, a suprasellar mass, and pulmonary infiltration. Biopsies from retrobulbar and bronchial sites showed similar inflammatory tissue. His disease resolved with pulsed corticosteroid therapy.

Symptomatic and asymptomatic accessory navicular bones: findings of Tc-99m MDP bone scintigraphy.

AIM: The accuracy of bone scintigraphy in diagnosing symptomatic accessory navicular bones has not been well studied. We conducted a retrospective study to explore the results and use of scintigraphy in symptomatic and asymptomatic accessory navicular bones. MATERIALS AND METHODS: Thirteen patients with a total of 13 symptomatic and 10 asymptomatic accessory navicular bones were included in the study. We used a scoring system to grade the scintigraphic abnormalities. The patients' symptoms and scintigraphic findings were recorded. RESULTS: Though focally increased radiopharmaceutical uptake was observed in all symptomatic accessory naviculars, half of the asymptomatic accessory navicular bones had the same manifestations. The scoring system was of no value in differentiating symptomatic from asymptomatic accessory navicular bones. CONCLUSION: Bone scintigraphy is a sensitive but not a specific tool for diagnosing a symptomatic accessory navicular.

Peritoneal scintigraphy for diagnosing periumbilical leakage in a patient on continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) offers several advantages over hemodialysis for patients with end-stage renal disease; however, this technique also includes many documented complications. A case with clinical suspicion of dialysate leakage on CAPD was investigated by peritoneal scintigraphy using technetium-99m macroaggregated human albumin (99mTc-MAA). Peritoneal scintigraphy showed radiotracer accumulation over the periumbilical area at 2 hours 30 minutes after intraperitoneal infusion of 99mTc-MAA. Six hours of imaging revealed more apparent radioactivity at the same site. This study is to illustrate the simple diagnostic helpfulness of peritoneal scintigraphy in a patient with a CAPD-related structural defect.

Evaluation and validation of ureteric jet index by glomerular filtration rate.

RATIONALE AND OBJECTIVES: Ureteric jet index (UJI), a newly developed technique derived from color Doppler ultrasonography, may hold promise in evaluating renal function because of its ability to evaluate individual renal function and the use of nonionizing radiation. To assess the usefulness of UJI, the authors in this study analyzed the relation between UJI and the glomerular filtration rate (GFR). METHODS: Fifteen adult patients with a wide range of renal function were included in this study. Subjects were well hydrated before color Doppler ultrasonography examinations. The UJI formula was: Vmean (average jet velocity) x D (jet duration) x F (jet frequency). GFR was calculated by the radionuclide method. Correlations between UJI, serum creatinine, and GFR were analyzed. RESULTS: Ureteric jet index had only a fair correlation with GFR. The coefficient of correlation value was 0.61, and the standard error of estimate of GFR was 17.9 mL/min. CONCLUSIONS: With the measurement of UJI, color Doppler ultrasound can provide both structural images and individual renal function information. It could substitute for a renal scan in determining individual renal function when a radionuclide examination is unavailable. Even if a renal scan were available, UJI can play a valuable role in the ultrasound examination of patients with suspected impaired renal function, providing further assessment of individual renal function.

Technetium-99m(V)-DMSA and gallium-67 in the assessment of bone and joint infection.

UNLABELLED: The aim of our study was to investigate the diagnostic value of scans with 99mTc(V)-dimercaptosuccinic acid (DMSA) to localize bone and joint infection compared with scans using 67Ga. METHODS: Thirty-six patients referred for investigation of bone and joint infection were studied. In all patients, a bone scan was obtained initially. Subsequently, comparative scans with 99mTc(V)-DMSA and 67Ga were performed 1 wk apart. Microbiological findings, pathologic findings and/or clinical follow-up (until symptoms disappeared) were considered to be proof of the presence of bone and joint infection. RESULTS: Technetium-99m (V)-DMSA showed greater sensitivity and accuracy than 67Ga in the assessment of bone and joint infection, although the difference was not statistically significant. CONCLUSION: In comparison with a 67Ga scan, a 99mTc(V)-DMSA scan, in combination with a bone scan, is a reliable way to diagnose bone and joint infection. Both tracers were useful in the diagnosis of bone and joint infection.

Reflex sympathetic dystrophy syndrome in stroke patients with hemiplegia-three phase bone scintigraphy and clinical characteristics.

In an attempt to investigate the correlation between three phase bone scintigraphy (TPBS) and the clinical manifestation of reflex sympathetic dystrophy syndrome (RSDS) in the upper extremity of hemiplegia, we collected 30 patients with cerebral vascular accidents (CVA) confirmed by head computed tomography (infarction or hemorrhage) within 3 months of their CVA event. All patients received TPBS after admission. Clinical assessment for the development of the RSDS was done at least 3 months (268 +/- 120 days) after the stroke. The correlation between the development of RSD and certain clinical variables (including sex, age, side affected, caused of stroke, and motor stage) were analyzed. Twelve patients (40%) manifested definite or probable RSDS, as assessed by Tepperman's criteria, during the follow-up period. Nineteen patients (63%) exhibited radionuclide evidence of RSDS based on delayed bone scan criteria performed within 3 months (43 +/- 25 days) of the stroke. The positive delayed image of TPBS demonstrated a sensitivity = 92%; specificity = 56%; positive predictive value = 58%, and negative predictive value = 91%. The Kappa statistics for agreement between positive bone scan and RSDS development was 70% (Kappa = 0.43, p < 0.05). Neither sex, age, side affected, cause of stroke, or motor stage had a significant correlation with clinical RSDS. In conclusion, TPBS is a useful screening tool for the development of RSD in hemiplegic patients. However, the diagnosis of RSDS depends on the clinical evaluation and that TPBS as an adjunct assessment of RSDS must be interpreted with caution.