Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium-labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe.

BACKGROUND: PET/CT lymphoscintigraphy using 89Zr-nanocolloidal albumin has the potential to improve the preoperative identification of sentinel lymph nodes (SLNs), especially if located in the near proximity of the primary tumour. This study aims to demonstrate the feasibility of PET/CT lymphoscintigraphy followed by intraoperative detection of 89Zr-nanocolloidal albumin containing SLNs with the use of a handheld high-energy gamma probe. METHODS: PET/CT lymphoscintigraphy was performed after peritumoural injection of 89Zr-nanocolloidal albumin in five patients with oral cavity carcinoma planned for surgical resection. SLN biopsy procedure was performed 18 h later. SLNs were detected using detailed information of PET/CT and the high-energy gamma probe. RESULTS: In all patients, SLNs were identified on PET/CT lymphoscintigraphy. Intraoperative detection using the high-energy gamma probe was possible in 10 of 13 SLNs, at a short distance from the SLN. CONCLUSIONS: This study demonstrates that intraoperative detection of SLNs containing 89Zr-nanocolloidal albumin using a handheld high-energy gamma probe is feasible, but its clinical use and sensitivity seem to be limited. TRIAL REGISTRATION: CCMO NL37222.092.11.

Multiregional Tumor Drug-Uptake Imaging by PET and Microvascular Morphology in End-Stage Diffuse Intrinsic Pontine Glioma.

Inadequate tumor uptake of the vascular endothelial growth factor antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma. Methods: By combining data from a PET imaging study using 89Zr-labeled bevacizumab and an autopsy study, a 1-on-1 analysis of multiregional in vivo and ex vivo 89Zr-bevacizumab uptake, tumor histology, and vascular morphology in a diffuse intrinsic pontine glioma patient was performed. Results: In vivo 89Zr-bevacizumab measurements showed heterogeneity between lesions. Additional ex vivo measurements and immunohistochemistry of cervicomedullary metastasis samples showed uptake to be highest in the area with marked microvascular proliferation. In the primary pontine tumor, all samples showed similar vascular morphology. Other histologic features were similar between the samples studied. Conclusion: In vivo 89Zr-bevacizumab PET serves to identify heterogeneous uptake between tumor lesions, whereas subcentimeter intralesional heterogeneity could be identified only by ex vivo measurements. 89Zr-bevacizumab uptake is enhanced by vascular proliferation, although our results suggest it is not the only determinant of intralesional uptake heterogeneity.

Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve.

Importance: At present, the choice of noninvasive testing for a diagnosis of significant coronary artery disease (CAD) is ambiguous, but nuclear myocardial perfusion imaging with single-photon emission tomography (SPECT) or positron emission tomography (PET) and coronary computed tomography angiography (CCTA) is predominantly used for this purpose. However, to date, prospective head-to-head studies are lacking regarding the diagnostic accuracy of these imaging modalities. Furthermore, the combination of anatomical and functional assessments configuring a hybrid approach may yield improved accuracy. Objectives: To establish the diagnostic accuracy of CCTA, SPECT, and PET and explore the incremental value of hybrid imaging compared with fractional flow reserve. Design, Setting, and Participants: A prospective clinical study involving 208 patients with suspected CAD who underwent CCTA, technetium 99m/tetrofosmin-labeled SPECT, and [15O]H2O PET with examination of all coronary arteries by fractional flow reserve was performed from January 23, 2012, to October 25, 2014. Scans were interpreted by core laboratories on an intention-to-diagnose basis. Hybrid images were generated in case of abnormal noninvasive anatomical or functional test results. Main Outcomes and Measures: Hemodynamically significant stenosis in at least 1 coronary artery as indicated by a fractional flow reserve of 0.80 or less and relative diagnostic accuracy of SPECT, PET, and CCTA in detecting hemodynamically significant CAD. Results: Of the 208 patients in the study (76 women and 132 men; mean [SD] age, 58 [9] years), 92 (44.2%) had significant CAD (fractional flow reserve ≤0.80). Sensitivity was 90% (95% CI, 82%-95%) for CCTA, 57% (95% CI, 46%-67%) for SPECT, and 87% (95% CI, 78%-93%) for PET, whereas specificity was 60% (95% CI, 51%-69%) for CCTA, 94% (95% CI, 88%-98%) for SPECT, and 84% (95% CI, 75%-89%) for PET. Single-photon emission tomography was found to be noninferior to PET in terms of specificity (P < .001) but not in terms of sensitivity (P > .99) using the predefined absolute margin of 10%. Diagnostic accuracy was highest for PET (85%; 95% CI, 80%-90%) compared with that of CCTA (74%; 95% CI, 67%-79%; P = .003) and SPECT (77%; 95% CI, 71%-83%; P = .02). Diagnostic accuracy was not enhanced by either hybrid SPECT and CCTA (76%; 95% CI, 70%-82%; P = .75) or by PET and CCTA (84%; 95% CI, 79%-89%; P = .82), but resulted in an increase in specificity (P = .004) at the cost of a decrease in sensitivity (P = .001). Conclusions and Relevance: This controlled clinical head-to-head comparative study revealed PET to exhibit the highest accuracy for diagnosis of myocardial ischemia. Furthermore, a combined anatomical and functional assessment does not add incremental diagnostic value but guides clinical decision-making in an unsalutary fashion.

Human Dosimetry of the N-Methyl-d-Aspartate Receptor Ligand 11C-GMOM.

The methylguanidine derivative 11C-GMOM (11C-labeled N-(2-chloro-3-thiomethylphenyl)-N'-(3-methoxyphenyl)-N'-methylguanidine) has been used successfully to quantify N-methyl-d-aspartate (NMDA) receptor binding in humans. The purpose of the present study was to estimate the 11C-GMOM radiation dose in healthy humans. Methods: After 11C-GMOM injection, 3 female and 2 male subjects underwent 10 consecutive whole-body PET scans in approximately 77 min. Seven source organs were defined manually, scaled to a sex-specific reference, and residence times were calculated for input into OLINDA/EXM software. Accepted tissue-weighting factors were used to calculate the effective dose. Results: The mean absorbed radiation doses in source organs ranged from 7.7 µGy·MBq-1 in the brain to 12.7 µGy·MBq-1 in the spleen. The effective dose (±SD) was 4.5 ± 0.5 µSv·MBq-1Conclusion: The effective dose of 11C-GMOM is at the lower end of the range seen for other 11C-labeled ligands, allowing for serial PET scanning in a single subject.

Calibration of PET/CT scanners for multicenter studies on differentiated thyroid cancer with (124)I.

BACKGROUND: Studies on imaging of differentiated thyroid cancer (DTC) using (124)I often require a multicenter approach, as the prevalence of DTC is low. Calibration of participating scanners is required to obtain comparable quantification. As determination of a well-defined range of recovery coefficients is complicated for various reasons, a simpler approach based on the assumption that the iodine uptake is highly focal with a background that significantly lacks radioactivity might be more efficient. For each scanner, a linear conversion between known and observed activity can be derived, allowing quantification that can be traced to a common source for all scanners within one study-protocol. The aim of this paper is to outline a procedure using this approach in order to set up a multicenter calibration of PET/CT scanners for (124)I. METHODS: A cylindrical polyethylene phantom contained six 2-ml vials with reference activities of ~2, 10, 20, 100, 400, and 2000 kBq, produced by dilution from a known activity. The phantom was scanned twice on PET/CT scanners of participating centers within 1 week. For each scanner, the best proportional and linear fit between measured and known activities were derived and based on statistical analyses of the results of all scanners; it was determined which fit should be applied. In addition, a Bland-Altman analysis was done on calibrated activities with respect to reference activities to asses the relative precision of the scanners. RESULTS: Nine Philips (vendor A) and nine Siemens (vendor B) PET/CT scanners were calibrated in a time period of 3 days before and after the reference time. No significant differences were detected between the two subsequent scans on any scanner. Six fitted intercepts of vendor A were significantly different from zero, so the linear model was used. Intercepts ranged from -8 to 26 kBq and slopes ranged from 0.80 to 0.98. Bland-Altman analysis of calibrated and reference activities showed that the relative error of calibrated activities was smaller than that of uncalibrated activities. CONCLUSIONS: A simplified multicenter calibration procedure for PET/CT scans that show highly focal uptake and negligible background is feasible and results in more precise quantification. Our procedure can be used in multicenter (124)I PET scans focusing on (recurrent) DTC.

PET/CT-derived whole-body and bone marrow dosimetry of 89Zr-cetuximab.

UNLABELLED: PET/CT imaging allows for image-based estimates of organ and red marrow (RM) residence times. The aim of this study was to derive PET/CT-based radiation dosimetry for (89)Zr-cetuximab, with special emphasis on determining RM-absorbed dose. METHODS: Seven patients with colorectal cancer received 36.9 ± 0.8 MBq of (89)Zr-cetuximab within 2 h after administration of a therapeutic dose of 500 mg·m(-2) of cetuximab. Whole-body PET/CT scans and blood samples were obtained at 1, 24, 48, 94, and 144 h after injection. RM activity concentrations were calculated from manual delineation of the lumbar vertebrae and blood samples, assuming a fixed RM-to-plasma activity concentration ratio (RMPR) of 0.19. The cumulated activity was calculated as the area under the curve of the organ time-activity data (liver, lungs, kidneys, spleen, and RM), assuming physical decay after the last scan. The residence time for each organ was derived by dividing the cumulated activity with the total injected activity. The residence time in the remainder of the body was calculated as the maximum possible residence time minus the sum of residence time of source organs, assuming no excretion during the time course of the scans. The (self and total) RM- and organ-absorbed doses and effective whole-body radiation dose were obtained using dose conversion factors from OLINDA/EXM 1.1. Several simplified 3-time-point dosimetry approaches were also evaluated. RESULTS: The first approach yielded self and total RM doses of 0.17 ± 0.04 and 0.51 ± 0.06 mGy·MBq(-1), respectively. The second approach deviated by -21% in self-dose and -6% in total dose. RMPR increased over time in 5 of 7 patients. The highest (89)Zr-absorbed dose was observed in the liver with 2.60 ± 0.78 mGy·MBq(-1), followed by the kidneys, spleen, and lungs, whereas the effective whole-body dose was 0.61 ± 0.09 mSv·MBq(-1). The simplified 3-time-point (1, 48, and 144 h) dosimetry approach deviated by at most 4% in both organ-absorbed doses and effective dose. CONCLUSION: Although the total RM dose estimates obtained with the 2 approaches differed only by at most 6%, the image-based approach is preferred because it accounts for nonconstant RMPR. The number of successive scans can be reduced to 3 without affecting effective dose estimates.

Quantification of 18F-Fluoride Kinetics: Evaluation of Simplified Methods.

UNLABELLED: (18)F-fluoride PET is a promising noninvasive method for measuring bone metabolism and bone blood flow. The purpose of this study was to assess the performance of various clinically useful simplified methods by comparing them with full kinetic analysis. In addition, the validity of deriving bone blood flow from K1 of (18)F-fluoride was investigated using (15)O-H2O as a reference. METHODS: Twenty-two adults (mean age ± SD, 44.8 ± 25.2 y), including 16 patients scheduled for bone surgery and 6 healthy volunteers, were studied. All patients underwent dynamic (15)O-H2O and (18)F-fluoride scans before surgery. Ten of these patients had serial PET measurements before and at 2 time points after local bone surgery. During all PET scans, arterial blood was monitored continuously. (18)F-fluoride data were analyzed using nonlinear regression (NLR) and several simplified methods (Patlak and standardized uptake value [SUV]). SUV was evaluated for different time intervals after injection and after normalizing to body weight, lean body mass, and body surface area, and simplified measurements were compared with NLR results. In addition, changes in SUV and Patlak-derived fluoride influx rate (Ki) after surgery were compared with corresponding changes in NLR-derived Ki. Finally, (18)F-fluoride K1 was compared with bone blood flow derived from (15)O-H2O data, using the standard single-tissue-compartment model. RESULTS: K1 of (18)F-fluoride correlated with measured blood flow, but the correlation coefficient was relatively low (r = 0.35, P < 0.001). NLR resulted in a mean Ki of 0.0160 ± 0.0122, whereas Patlak analysis, for the interval 10-60 min after injection, resulted in an almost-identical mean Ki of 0.0161 ± 0.0117. The Patlak-derived Ki, for 10-60 min after injection, showed a high correlation with the NLR-derived Ki (r = 0.976). The highest correlation between Ki and lean body mass-normalized SUV was found for the interval 50-60 min (r = 0.958). Finally, changes in SUV correlated significantly with those in Ki (r = 0.97). CONCLUSION: The present data support the use of both Patlak and SUV for assessing fluoride kinetics in humans. However, (18)F-fluoride PET has only limited accuracy in monitoring bone blood flow.

Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial.

RATIONALE: Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS), by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC) may inhibit this process and thereby improve patient outcome. METHODS: A prospective randomized, saline-controlled, single-blinded clinical trial was performed in the intensive care units of two university hospitals, and patients with ARDS were included within 24 h after meeting inclusion criteria. INTERVENTION: A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38). OUTCOMES: The primary outcome parameter was the pulmonary leak index (PLI) of 67Gallium-transferrin as a measure of alveolocapillary permeability and secondary outcomes were disease severity scores and ventilator-free days, among others. RESULTS: Baseline characteristics were similar; in 87% of patients the PLI was above normal and in 90% mechanical or non-invasive ventilation was instituted at a median lung injury score of 2.5. There was no evidence that Rh-APC treatment affected the PLI or attenuated lung injury and sequential organ failure assessment scores. Mean ventilator-free days amounted to 14 (rh-APC) and 12 days (saline, P = 0.35). 28-day mortality was 6% in rh-APC- and 18% in saline-treated patients (P = 0.12). There was no difference in bleeding events. The study was prematurely discontinued because rh-APC was withdrawn from the market. CONCLUSION: There is no evidence that treatment with intravenous rh-APC during 4 days for infectious or inflammatory ARDS ameliorates increased alveolocapillary permeability or the clinical course of ARDS patients. We cannot exclude underpowering. TRIAL REGISTRATION: Nederlands Trial Register ISRCTN 52566874.

Radiation dose of the P-glycoprotein tracer 11C-laniquidar.

UNLABELLED: Resistance to current drug therapy is an important issue in the treatment of epilepsy. Inadequate access of central nervous system drugs to their targets in the brain may be caused by overexpression or overactivity of multidrug transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier. Laniquidar, an inhibitor of P-gp, has been labeled with (11)C for use in PET studies of P-gp expression in humans. Given potential interspecies differences in biodistribution, the purpose of this study was to ensure safe use of (11)C-laniquidar by determining the dosimetry of (11)C-laniquidar using whole-body PET studies. METHODS: Six healthy volunteers were subjected to a series of 10 whole-body PET scans within approximately 70 min. Five blood samples were taken during the series. RESULTS: High uptake of (11)C-laniquidar was seen in liver, spleen, kidneys, and lung, whereas brain uptake was low. The effective dose for (11)C-laniquidar was 4.76 ± 0.13 and 3.69 ± 0.01 µSv·MBq(-1) for women and men, respectively. CONCLUSION: Biodistribution and measured effective dose indicate that (11)C-laniquidar is a safe tracer for PET imaging, with a total dose of about 2 mSv for a brain PET/CT protocol.

Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin's lymphoma using 89Zr-ibritumomab tiuxetan and PET.

PURPOSE: Positron emission tomography (PET) with (89)Zr-ibritumomab tiuxetan can be used to monitor biodistribution of (90)Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of (90)Y-ibritumomab tiuxetan in humans on the basis of (89)Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of (90)Y-ibritumomab tiuxetan influences biodistribution of (89)Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with (89)Zr-ibritumomab tiuxetan can be used to predict biodistribution of (90)Y-ibritumomab tiuxetan and the dose-limiting organ during therapy. METHODS: Seven patients with relapsed B-cell non-Hodgkin's lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of ~70 MBq (89)Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg (90)Y-ibritumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data. RESULTS: The highest (90)Y absorbed dose was observed in liver (3.2 ± 1.8 mGy/MBq) and spleen (2.9 ± 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 ± 0.04 mGy/MBq, and the effective dose was 0.87 ± 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on (89)Zr-ibritumomab tiuxetan images was high (Pearson correlation coefficient r = 0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r = 0.75). CONCLUSION: Biodistribution of (89)Zr-ibritumomab tiuxetan is not influenced by simultaneous therapy with (90)Y-ibritumomab tiuxetan, and (89)Zr-ibritumomab tiuxetan scout scans can thus be used to predict biodistribution and dose-limiting organ during therapy. Absorbed doses to spleen were lower than those previously estimated using (111)In-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.

Absolute quantification of [(11)C]docetaxel kinetics in lung cancer patients using positron emission tomography.

PURPOSE: Tumor resistance to docetaxel may be associated with reduced drug concentrations in tumor tissue. Positron emission tomography (PET) allows for quantification of radiolabeled docetaxel ([(11)C]docetaxel) kinetics and might be useful for predicting response to therapy. The primary objective was to evaluate the feasibility of quantitative [(11)C]docetaxel PET scans in lung cancer patients. The secondary objective was to investigate whether [(11)C]docetaxel kinetics were associated with tumor perfusion, tumor size, and dexamethasone administration. EXPERIMENTAL DESIGN: Thirty-four lung cancer patients underwent dynamic PET-computed tomography (CT) scans using [(11)C]docetaxel. Blood flow was measured using oxygen-15 labeled water. The first 24 patients were premedicated with dexamethasone. For quantification of [(11)C]docetaxel kinetics, the optimal tracer kinetic model was developed and a noninvasive procedure was validated. RESULTS: Reproducible quantification of [(11)C]docetaxel kinetics in tumors was possible using a noninvasive approach (image derived input function). Thirty-two lesions (size ≥4 cm(3)) were identified, having a variable net influx rate of [(11)C]docetaxel (range, 0.0023-0.0229 mL·cm(-3)·min(-1)). [(11)C]docetaxel uptake was highly related to tumor perfusion (Spearman's ρ = 0.815;P < 0.001), but not to tumor size (Spearman's ρ = -0.140; P = 0.446). Patients pretreated with dexamethasone showed lower [(11)C]docetaxel uptake in tumors (P = 0.013). Finally, in a subgroup of patients who subsequently received docetaxel therapy, relative high [(11)C]docetaxel uptake was related with improved tumor response. CONCLUSIONS: Quantification of [(11)C]docetaxel kinetics in lung cancer was feasible in a clinical setting. Variable [(11)C]docetaxel kinetics in tumors may reflect differential sensitivity to docetaxel therapy. Our findings warrant further studies investigating the predictive value of [(11)C]docetaxel uptake and the effects of comedication on [(11)C]docetaxel kinetics in tumors.

Plasma protein levels are markers of pulmonary vascular permeability and degree of lung injury in critically ill patients with or at risk for acute lung injury/acute respiratory distress syndrome.

OBJECTIVES: To evaluate the diagnostic value of plasma protein levels for pulmonary vascular permeability and acute respiratory distress syndrome. During acute lung injury and acute respiratory distress syndrome, increased vascular permeability induces protein-rich fluid extravasation. We hypothesized that plasma protein levels predict increased vascular permeability and acute respiratory distress syndrome. DESIGN: A prospective, observational study. PATIENTS: Eighty-three consecutive, mechanically ventilated patients with or at risk for acute lung injury/acute respiratory distress syndrome, of whom 18 had sepsis. Patients with increased pulmonary capillary wedge pressures or central venous pressures were excluded. INTERVENTIONS: Patients were subjected to pulmonary capillary wedge pressure/central venous pressure-guided fluid loading with saline or colloid fluids. MEASUREMENTS AND MAIN RESULTS: We measured plasma albumin and transferrin levels and determined the Gallium-transferrin pulmonary leak index, the American European Consensus Conference criteria, and the lung injury score. Measurements were performed before and after fluid loading to evaluate effects of fluid loading. Plasma albumin and transferrin levels were approximately 30% lower in acute respiratory distress syndrome than patients with acute lung injury (p < .01) and patients without lung injury (p < .05). Protein levels inversely related to the pulmonary leak index (standardized regression coefficient -0.28, p < .001 for albumin; standardized regression coefficient -0.30, p = .003 for transferrin) and the lung injury score (standardized regression coefficient -0.19, p = .01 for albumin), independently of presence of sepsis, severity of disease, and fluid loading. Albumin and transferrin levels had a high sensitivity (77-93%) and negative predictive value (80-98%) for elevated pulmonary vascular permeability and acute respiratory distress syndrome (American European Consensus Conference criteria and lung injury score). The addition of hypoalbuminemia (<17.5 g/L) and hypotransferrinemia (<0.98 g/L) as criteria to the American European Consensus Conference criteria or the lung injury score increased their predictive values for elevated pulmonary vascular permeability. CONCLUSIONS: In critically ill patients, decreased plasma albumin and transferrin levels parallel increased pulmonary vascular permeability irrespective of underlying disease and fluid status. While normal levels help to exclude acute respiratory distress syndrome, hypoalbuminemia and hypotransferrinemia increase the diagnostic accuracy of the American European Consensus Conference criteria and lung injury score for elevated pulmonary vascular permeability.

H9c2 cardiomyoblasts produce thyroid hormone.

Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125 I, we found that 125 I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125 I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.

FDG PET in lymphoma: the need for standardization of interpretation. An observer variation study.

OBJECTIVE: To measure and describe patterns of interobserver variation in visual interpretation of 18-FDG PET in malignant lymphoma. METHODS: Eleven nuclear medicine physicians with different levels of PET experience independently reviewed 37 18F-FDG PET scans of lymphoma patients (10 obtained at presentation, 27 during or after therapy). They were requested to identify and localize suspicious lymphoma sites and to assign a stage to the baseline scans, and to interpret the remaining scans for the presence of viable lymphoma. Individual (extra-)nodal regions were assessed for the likelihood of malignancy as positive, negative or equivocal. These results were compared to expert readings after dichotomization in conservative and sensitive reading classifications. RESULTS: Sixty-one percent and 56% (using sensitive and conservative reading, respectively) of the baseline scans were scored in accordance with the experts. Fourteen of the 27 scans obtained for therapy evaluation with viable tumour sites were scored in accordance with the experts in 82% and 94% of the patients, using conservative and sensitive reading, respectively. The 13 negative scans were scored in agreement with the experts in only 45% of the cases. False positivity pertained especially to the neck, periclavicular, axilla, mediastinum, lung and bone marrow. More experienced observers tended to have fewer false negative scores. CONCLUSION: There are substantial disparities among nuclear medicine physicians' interpretations of FDG PET scans of lymphoma patients, which may affect patient care and results of multi-institutional clinical trials. A well-defined set of criteria is urgently needed to improve consistency.

Observer variation of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography in mediastinal staging of non-small cell lung cancer as a function of experience, and its potential clinical impact.

PURPOSE: To test the extent of variation among nuclear medicine physicians with respect to staging non-small cell lung cancer with positron emission tomography (PET). PROCEDURES: Two groups of nuclear medicine physicians with different levels of PET experience reviewed 30 PET scans. They were requested to identify and localize suspicious mediastinal lymph nodes (MLN) using standardized algorithms. Results were compared between the two groups, between individuals, and with expert reading. RESULTS: Overall we found good interobserver agreement (kappa 0.65). Experience with PET translated into a better ability to localize MLN stations (68% vs. 51%, respectively), and experienced readers appeared to be more familiar with translating PET readings into clinically useful statements. CONCLUSIONS: Although our results suggest that clinical experience with PET increases observers' ability to read and interpret results from PET adequately, there is room for improvement. Experience with PET does not necessarily improve the accuracy of image interpretation.

Attenuation-corrected vs. nonattenuation-corrected 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography in oncology: a systematic review.

PURPOSE: To perform a systematic review and meta-analysis to determine the diagnostic accuracy of attenuation-corrected (AC) vs. nonattenuation-corrected (NAC) 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) in oncological patients. PROCEDURES: Following a comprehensive search of the literature, two reviewers independently assessed the methodological quality of eligible studies. The diagnostic value of AC was studied through its sensitivity/specificity compared to histology, and by comparing the relative lesion detection rate reported with NAC-PET vs. AC, for full-ring and dual-head coincidence PET (FR- and DH-PET, respectively). RESULTS: Twelve studies were included. For FR-PET, the pooled sensitivity/specificity on a patient basis was 64/97% for AC and 62/99% for NAC, respectively. Pooled lesion detection with NAC vs. AC was 98% [95% confidence interval (95% CI): 96-99%, n = 1,012 lesions] for FR-PET, and 88% (95% CI:81-94%, n = 288 lesions) for DH-PET. CONCLUSIONS: Findings suggest similar sensitivity/specificity and lesion detection for NAC vs. AC FR-PET and significantly higher lesion detection for NAC vs. AC DH-PET.

Cardiac response is greater for colloid than saline fluid loading after cardiac or vascular surgery.

OBJECTIVE: To study the effects on volume expansion and myocardial function of colloids or crystalloids in the treatment of hypovolaemic hypotension after cardiac and major vascular surgery. DESIGN AND SETTING: A single-centre, single-blinded, randomized clinical trial at the intensive care unit of a university hospital. PATIENTS AND METHODS: Patients (n=67) were subjected to a 90-min filling pressure-guided fluid challenge with saline 0.9% or the colloids gelatin 4%, hydroxyethyl starch 6% or albumin 5%. Biochemical variables and haemodynamics (transpulmonary thermodilution) were measured. RESULTS: An amount of 1800 (1300-1800) ml of saline or 1600 (750-1800) ml of colloid solution (P< 0.005) was infused. Colloid osmotic pressure (COP) decreased in the saline group and increased in the colloid groups (P< 0.001). Plasma volume increased by 3.0% (-18 to 24) in the saline versus 19% (-11 to 50) in the colloid groups (P< 0.001). Cardiac index increased by median 13% (ns) in the saline group and by 22% in the colloid groups (P<0.005). The rise in left ventricular stroke work index was greater in the colloid than in the saline groups. The different colloids were equally effective. The rise in cardiac index related to the rise in plasma volume and global end-diastolic volume, confirming plasma volume and preload augmentation by the fluid loading. CONCLUSION: After cardiac or major vascular surgery, the pressure- and time-guided fluid response is dependent on the type of fluid used. Colloid fluid loading leads to a greater increase in preload-recruitable cardiac and left ventricular stroke work indices than that with saline, because of greater plasma volume expansion following an increase in plasma COP.

Interobserver variability in the semi-quantitative assessment of 201Tl SPECT in cerebral gliomas.

OBJECTIVES: 201Tl SPECT is used successfully in the diagnosis of recurrent supratentorial glioma and in the evaluation of its response to chemotherapy. However, different methods are used to measure relative tracer uptake in tumour and background. The objective of this study was to assess the interobserver variability of such methods, and, if possible, to provide nomograms for data conversion. METHODS: Using baseline and follow-up SPECT scans from 20 patients with recurrent glioma treated with chemotherapy, three observers applied manual and semi-automatic ROI techniques to define activity in tumour (manual, semi-automatic) as well as in reference tissue (scalp, mirror, hemisphere). RESULTS: All tumour ROI techniques had intra-class correlation coefficients (ICC) > or = 0.80 indicating almost perfect agreement. The main source of variation with the manual techniques was the tumour intensity; with the semi-automatic method, observer agreement was independent of the level of tumour activity. Agreement for background ROIs was also adequate, but the mirror technique tended to perform poorer at follow-up SPECT scans (ICC 0.68). Measurement of fractional change during treatment revealed no significant differences between observers for any of the investigated ROI methodology variants. Conversion of quantitative methods to measure fractional change was possible using linear regression analysis. CONCLUSION: 201Tl SPECT in recurrent glioma appears to be a robust method with acceptable interobserver variability. The clinical field in neuro-oncology should consider including 201Tl SPECT parameters in monitoring response to chemotherapy.

The sentinel node in cervical cancer: scintigraphy and laparoscopic gamma probe-guided biopsy.

The sentinel node (SN) procedure has been proven to be a valuable technique in the staging and treatment of a number of solid tumours. We evaluated the feasibility of SN biopsy with a laparoscopic gamma probe and dye guidance in 34 patients with clinically localised cervical cancer. After peritumoural injection of 140 MBq 99mTc colloidal albumin, dynamic and late static images were obtained. Just before the laparoscopic procedure, blue dye was injected. Blue and radioactive lymph nodes were excised followed by a regular lymphadenectomy. Lymphoscintigraphy revealed 70 SNs in 50 basins during dynamic imaging and 83 SNs in 63 basins at late imaging. SNs were visualised in 97% of the patients, bilaterally in 30 and unilaterally in three. Seventy-four of the 105 radioactive lymph nodes that were excised laparoscopically were considered to be SNs, 53 being blue as well, and were sent for frozen section. Nine foci that had been seen on scintigraphy could not be found either intraoperatively or in the remaining lymphadenectomy specimen. Four blue nodes were excised in three of five basins that had shown no foci during scintigraphy. In 17 basins of 12 patients, tumour-positive lymph nodes were found. In one of them a micrometastasis was found in the hysterectomy specimen while the lymphadenectomy did not contain any metastases (sensitivity 92%). Based on SN histology, the treatment was altered in nine patients (26%). We conclude that laparoscopic SN biopsy is feasible in cervical cancer and may result in custom-designed treatment strategies with a reduction in morbidity.

Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity?

INTRODUCTION: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear. METHODS: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1-11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for 67Gallium (67Ga)-transferrin (upper limit of normal 14.1 x 10(-3)/min) was measured. RESULTS: The PLI ranged between 7.5 and 14.0 x 10(-3)/min in the study patients. Two patients received a course of acyclovir and all survived. CONCLUSIONS: The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs.