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Context: Approximately 10% of pheochromocytomas are malignant with a 5-yr survival rate of less than 40%. Promising results have been published on single high-dosage [131I]metaiodobenzylguanidine ([131I]MIBG) treatment for malignant pheochromocytoma. We present our experience with multiple intermediate-dosage [131I]MIBG therapy instead of single high-dosage therapy., Setting and Patients: The study took place at University Medical Centers and included two patients (one male, 36 yr of age, and one female, 43 yr of age) with widely spread metastatic pheochromocytoma and bad prognosis because of liver and lung metastases., Interventions: Instead of a single high dosage, these two patients were treated with multiple intermediate dosages of [131I]MIBG. The first patient received 37 GBq (1 Ci) [131I]MIBG in five sessions [7400 MBq (200 mCi) each; interval range, 2-11 months]; the second patient received 66.6 GBq (1.8 Ci) [131I]MIBG in 12 sessions [5550 MBq (150 mCi) each; interval range, 2-14 months]., Outcome Measures: We measured efficacy, toxicity, and survival., Results: Both patients had a complete symptomatic response and a partial tumor volume response. The first patient had a partial biochemical response, the second a complete biochemical response. In both cases, toxicity has been confined to nausea during treatment. Hematological toxicity was minimal, and both patients stayed euthyroid. The survival (so far) of these patients was 5 yr (clinical case 1) and 16 yr (clinical case 2) after initial diagnosis., Conclusions: Repeated intermediate-dosage [131I]MIBG treatment appears to be a reliable and well-tolerated radionuclide therapy and might be a useful adjunct in patients with malignant pheochromocytoma, providing longstanding palliation and prolonged survival.

Purpose: To compare diagnostic accuracy of computed tomography (CT), endoscopic ultrasonography (US), and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for assessment of response to neoadjuvant therapy in patients with esophageal cancer by using a systematic review of the literature., Materials and Methods: MEDLINE and EMBASE databases and Cochrane Database of Systematic Reviews were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. Summary receiver operating characteristic (ROC) analysis was used to summarize and compare the diagnostic accuracy of the three modalities., Results: Four studies with CT, 13 with endoscopic US, and seven with FDG PET met inclusion criteria. Percentages of the maximum score in regard to methodological quality ranged from 15% to 100%. Summary ROC analysis could be performed for three studies with CT, four with endoscopic US, and four with FDG PET. The maximum joint values for sensitivity and specificity were 54% for CT, 86% for endoscopic US, and 85% for FDG PET. Accuracy of CT was significantly lower than that of FDG PET (P < .006) and of endoscopic US (P < .003). Accuracy of FDG PET and that of endoscopic US were similar (P = .839). In all patients, CT was always feasible, whereas endoscopic US was not feasible in 6% of the patients, and FDG PET was not feasible in less than 1%., Conclusion: CT has poor accuracy for assessment of response to neoadjuvant therapy in patients with esophageal cancer. Endoscopic US and FDG PET have equivalent good accuracy, but endoscopic US is not always feasible after chemotherapy and radiation therapy. FDG PET seems to be a promising noninvasive tool for assessment of neoadjuvant therapy in patients with esophageal cancer.

Objective: The aim of this study was to evaluate the advantages and disadvantages of sentinel lymph node biopsy (SLNB) in patients with cutaneous melanoma., Design: Descriptive follow-up study., Method: In the period 1995-2004, 300 patients with cutaneous melanoma (Breslow thickness: > or = 1.0 mm) underwent SLNB and, in case of a tumour-positive result, regional lymph node dissection. Results of the SLNB procedure, postoperative complications, follow-up, recurrences, disease-free survival and disease-specific survival were evaluated., Results: The SLNB detection rate was 99%. 85 patients had a tumour-positive SLNB (28%) and underwent completion regional lymph node dissection; 215 patients underwent SLNB alone. The rate of postoperative complications after SLNB was 7%. With a median follow up of 51 months, the false-negative rate was 11%. The recurrence rate was 23% (SLNB negative: 19%; SLNB positive 34%; p = 0.005). In-transit metastases were found in 4% of the SLNB-negative group and in 20% of the SLNB-positive group (p < 0.001). The 5-year disease-free survival and disease-specific survival rates were 79% and 86%, respectively, in SLNB-negative patients and 57% and 71%, respectively, in SLNB-positive patients. Multivariate analysis showed that the independent prognostic factors for disease-free survival were presence of ulceration (p < 0.001) and SLNB positivity (p < 0.01). Prognostic factors for overall survival were presence of ulceration (p < 0.001) and male sex (p < 0.05), but not the SLNB results. Multivariate analysis also showed that SLNB positivity (p < 0.001) and presence of ulceration (p < 0.01) were independent prognostic factors for developing in-transit metastases., Conclusion: SLNB in patients with cutaneous melanoma is still only of prognostic value since survival benefit is not proven. Disadvantages of SLNB were the false-negative rate, the possibility of an increased risk of in-transit metastases in SLNB-positive patients, and postoperative complications. These must be kept in mind when offering patients SLNB.

Purpose: Dual-isotope simultaneous acquisition (DISA) single-photon emission computed tomography (SPECT) is an attractive technique as it permits assessment of both myocardial glucose metabolism and perfusion within a single session, but few data on its accuracy for the assessment of viability are available as yet. In the present study, DISA SPECT was compared with positron emission tomography (PET) for the detection of myocardial viability in normal and dysfunctional left ventricular (LV) myocardium., Methods: Fifty-eight patients with chronic coronary artery disease and LV dysfunction (LV ejection fraction 33+/-12%) were studied. Patients underwent a 1-day dipyridamole stress 99mTc-sestamibi/18F-fluorodeoxyglucose (18FDG) DISA SPECT and 13N-ammonia/18FDG PET protocol. Within 1 week, resting MRI was performed to assess contractile function. Comparison of PET and SPECT data was performed using both visual and quantitative analysis., Results: The correlation of normalised activities of the flow tracers 99mTc-sestamibi and 13N-ammonia was good (r = 0.82; p < 0.001). The correlation between the two 18FDG studies was also good (r = 0.83; p < 0.001). The agreement for the assessment of viability for all segments between DISA SPECT and PET was 82%, with a kappa-statistic of 0.59 (95% CI 0.53-0.64), without a significant difference; in dysfunctional segments only, the agreement was 82%, with a kappa-statistic of 0.63 (95% CI 0.56-0.70), without a significant difference. When the DISA SPECT data were analysed visually, the agreement between DISA SPECT and PET was 83%, with a kappa-statistic of 0.58 (95% CI 0.52-0.63), without a significant difference. Moreover, there was no significant difference between visual and quantitative DISA SPECT analysis for the detection of viability., Conclusion: This study shows an overall good agreement between 99mTc-sestamibi/18FDG DISA SPECT and PET for the assessment of myocardial viability in patients with severe LV dysfunction. Quantitative or visual analysis of the SPECT data did not influence the agreement with PET, suggesting that visual assessment may be sufficient for clinical purposes.

Objective: Recent case-control studies show associations of the minor T allele (of the C1858T single-nucleotide polymorphism corresponding to the R620W amino acid substitution) of PTPN22 with multiple autoimmune diseases, including systemic lupus erythematosus (SLE). We performed family-based association studies of this polymorphism in 4 independent cohorts containing SLE patients and their parents and/or other family members., Methods: A total of 2,689 individuals from 902 independent Caucasian families with SLE were genotyped using polymerase chain reaction pyrosequencing (cohorts 1 and 2) and the Sequenom MassArray system (cohorts 3 and 4). The transmission disequilibrium test (TDT) and the pedigree disequilibrium test (PDT) were conducted to assess the evidence of association., Results: The 1858 C > T allele frequencies of the parents showed no deviation from Hardy-Weinberg equilibrium within each cohort. No evidence of preferential transmission of the T allele from heterozygous parents to their affected offspring was observed in each of the 4 cohorts or in the combined sample. Consistent with the TDT result, the PDT analysis revealed no significant association between the T allele and SLE. In 54 of the 661 SLE patients (cohorts 1 and 3) with documented autoimmune thyroid disease, the T allele frequency was higher than in individuals with SLE alone (16.7% versus 8.5%; P = 0.008, odds ratio 2.16 [95% confidence interval 1.25-3.72])., Conclusion: The R620W polymorphism of the PTPN22 gene is not a major risk allele for SLE susceptibility in our sample of Caucasian individuals from northern America, the UK, or Finland, but it appears to be a risk factor for the concurrent autoimmune diseases of autoimmune thyroid disease and SLE.

Objective: On PET, the level of tissue glycolysis can be quantified by the accumulation of fluorine-18-fluorodeoxyglucose expressed as the standardized uptake value (SUV). The aims of this study were to investigate the relation between SUV and the stage of disease and whether SUV can be used to predict resectability and survival in patients with esophageal cancer., Conclusion: SUV can be used to predict resectability; however, SUV is not an independent factor that can be used to assess survival in patients with esophageal cancer.

Unlabelled: Because of improvements in diagnostic technology, the incidental detection of synchronous primary tumors during the preoperative work-up of patients with esophageal cancer has increased. The aim of this study was to determine the rate and clinical relevance of synchronous neoplasms seen on (18)F-FDG PET in staging of esophageal cancer., Methods: From January 1996 to July 2004, 366 patients with biopsy-proven malignancy of the esophagus underwent (18)F-FDG PET for initial staging. This series of patients was retrospectively reviewed for the detection of synchronous primary neoplasms., Results: Twenty synchronous primary neoplasms (5.5%) were identified in 366 patients. Eleven neoplasms were in the colorectum, 5 in the kidney, 2 in the thyroid gland, 1 in the lung, and 1 in the gingiva. One of the thyroid lesions and the lung lesion were erroneously interpreted as metastases, leading to incorrect upstaging of the esophageal tumor., Conclusion: (18)F-FDG PET detected unexpected synchronous primary neoplasms in 5.5% of patients with esophageal cancer. Sites of pathologic (18)F-FDG uptake should be confirmed by dedicated additional investigations before treatment, because synchronous neoplasms may mimic metastases.

A 51-year-old white woman with extreme fatigue, fever episodes, weight loss, leucocytosis and increased erythrocyte sedimentation rate showed diffuse high uptake of 18F-fluorodeoxyglucose in the entire aortic wall, which is characteristic of giant cell large-vessel arteritis, such as Takayasu disease.

A carcinoid crisis is a severe complication of the carcinoid syndrome that can arise in patients with advanced metastatic neuroendocrine tumors. It can be initiated by stress, catecholamines, and tumor manipulation. In this article, we report a case in which an injection with the catecholamine tracer 6-18F-fluorodihydroxyphenylalanine, used for PET, induced a carcinoid crisis. Octreotide can be used for treatment and should be available. Tracer injection should be slow.

In differentiated thyroid carcinoma 10-year survival rates amount to 80-95%. Because age at diagnosis varies widely, these survival rates strongly depend on age at presentation. The aim of the present study was to analyse the attributable risk factors, including therapy per se, on survival in thyroid cancer after proper adjustment for the baseline mortality rate in the general population and to elucidate the adverse treatment effects on survival. Initial treatment in 504 patients consisted of thyroidectomy and 131I ablation. High-dose 131I was administered for residual disease. Patients in complete remission underwent an annual physical examination and thyroglobulin measurements during TSH suppression. Survival time was studied after transformation to standardised survival time to adjust for the baseline mortality rate in the general population. Median follow-up since diagnosis was 9 years. The 10-year overall survival was 83% and disease-specific survival 91%. After initial treatment, persistent disease occurred in 75 patients (15%). In univariate analysis, T4, N1, M1 status and Hürthle cell type were prognostic for persistent and recurrent disease. Age was not prognostic for recurrent disease in multivariate analysis. The standardised survival time was not altered in disease-free patients. However, patients with persistent disease had a median standardised survival time of only 0.60 (95% confidence interval 0.47;0.72), ranging from 0 to above 1, independent of initial tumour status or age. The cumulative proportion of persistent disease was at least 20% of the whole group. Disease-free patients after thyroid carcinoma have a normal residual life span. In contrast, in cases of persistent disease the life expectancy ranges widely with its median being reduced to 60%. Overall, treatment including radioiodine is safe but unsuccessful in 20% of the patients. Age is not a disease-specific risk factor and should not be used as an independent factor in treatment algorithms.

Unlabelled: 18F-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET. Furthermore, the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated., Methods: Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT, endoscopic ultrasonography, and ultrasound of the neck. In addition, all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity., Results: 18F-FDG PET was able to detect all esophageal cancers, whereas 18F-FLT PET visualized the tumor in 8 of 10 patients. Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients. 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET, whereas 18F-FDG PET showed uptake in benign lesions in 2 patients. The uptake of 18F-FDG (median standardized uptake value [SUV(mean)], 6.0) was significantly higher than 18F-FLT (median SUV(mean), 3.4). Neither 18F-FDG maximum SUV (SUV(max)) nor 18F-FLT SUV(max) correlated with Ki-67 expression in the linear regression analysis., Conclusion: In this study, uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake. 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans. Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation.

Distant metastases or local invasion are frequently found during the explorative phase of surgery for esophageal cancer. This study was performed to determine the rate of patients with incurable disease encountered during exploration and to examine the impact of preoperative staging, including positron emission tomography (PET), on the number of unnecessary explorations. The records of 203 patients with esophageal cancer who were eligible for curative resection were retrospectively reviewed. The surgical reports were analyzed to obtain the reasons for abandoning resection. Furthermore, the different staging modalities according to the related time interval were reviewed for each patient to analyze the influence of them on the number of explorations. After exploratory surgery, resection was abandoned in 78 of the 203 patients (38%) because of distant metastases (n=59; 29%), metastatic spread and local irresectability (n=5; 2%), and local irresectability (n=14; 7%). In a logistic regression model with all preoperative staging modalities and the year of examination as independent variables, F-18-fluorodeoxyglucose (FDG)-PET) was the only modality that predicts intended curative resection in these patients (P<0.001). In patients with esophageal cancer who are suitable for potentially curative surgery, resection was abandoned mainly because of distant metastases encountered during exploration. The addition of FDG-PET may have reduced the rate of unnecessary surgery in this group of patients.

Background: Findings of mediastinal uptake of 131I after surgical treatment for differentiated thyroid carcinoma (DTC) are common, especially in young patients. Given the frequency of false-positive findings, a protocol for diagnostic and therapeutic strategies would be useful. With the goal of accurately selecting management strategies, the authors analyzed their data and data found elsewhere in the literature for correlations with the incidence of mediastinal 131I uptake and with treatment for patients exhibiting such 131I uptake., Methods: All patients with DTC who were treated between 1978 and 2000 at Groningen University Hospital (Groningen, The Netherlands) and who received adjuvant 131I ablation therapy were included in the current analysis, which involved retrospective review of all relevant data., Results: Five hundred four patients with DTC initially underwent total thyroidectomy, with additional 131I ablation performed for 489 of these patients. In 48 of 489 patients (9.8%), 131I uptake was seen in the mediastinum on a posttreatment scan. Analysis of those 48 patients and of cases in the literature demonstrated that serum thyroglobulin levels, risk status, and the presence of thymus on radiologic images were important in the surgical decision-making process., Conclusions: Mediastinal uptake of 131I on posttreatment scans was found in approximately 10% of patients after total thyroidectomy for DTC. Based on the current data and the data presented in the literature, the authors developed a flow chart for determining appropriate treatment strategies, which included mediastinal dissection for high-risk patients and for patients with serum thyroglobulin levels > 10 ng/mL.

Objective: After initial treatment with total thyroidectomy and radioiodine ablation, most follow-up protocols for patients with differentiated thyroid carcinoma contain cyclic diagnostic I-131 imaging and serum thyroglobulin measurements. The applied diagnostic I-131 doses vary between 37 and 370 MBq. The aim of this study was to determine the yield of a diagnostic scan with 370 MBq I-131 in patients with a negative diagnostic scan with 74 MBq I-131., Methods: Retrospective evaluation of 158 patients who received a high-dose diagnostic scan with 370 MBq I-131 because of a negative low-dose diagnostic scan with 74 MBq I-131. Special attention was paid to the patients with positive high-dose diagnostic scanning and undetectable serum thyroglobulin levels after thyroid hormone withdrawal., Results: In 127 (80%) of patients the 370 MBq I-131 scan was negative, just like the preceding low-dose scan. In 31 (20%) of patients abnormal uptake was present on the 370 MBq diagnostic scan. In 19 of these 31 patients serum thyroglobulin was undetectable. In 15/19 the high-dose diagnostic scan proved either false positive or demonstrated clinically irrelevant minor ablation rests. In only four patients (2.5%) did the high-dose diagnostic scans reveal possibly relevant uptake caused by residual differentiated thyroid cancer., Conclusion: In 98% of patients a 370 MBq dose of I-131 for diagnostic WBS had no additional value. The combination of a low-dose diagnostic I-131 scan using only 74 MBq combined with a serum Tg level measurement proved sufficient for correct clinical decision making regarding whether the patient requires additional I-131 therapy.

In recent years, [18F]-fluoro-3'-deoxy-3'-L: -fluorothymidine ([18F]FLT) has been developed as a proliferation tracer. Imaging and measurement of proliferation with PET could provide us with a non-invasive staging tool and a tool to monitor the response to anticancer treatment. In this review, the basis of [18F]FLT as a proliferation tracer is discussed. Furthermore, an overview of the current status of [18F]FLT-PET research is given. The results of this research show that although [18F]FLT is a tracer that visualises cellular proliferation, it also has certain limitations. In comparison with the most widely used PET tracer, [18F]FDG, [18F]FLT uptake is lower in most cases. Furthermore, [18F]FLT uptake does not always reflect the tumour cell proliferation rate, for example during or shortly after certain chemotherapy regimens. The opportunities provided by, and the limitations of, [18F]FLT as a proliferation tracer are addressed in this review, and directions are given for further research, taking into account the strong and weak points of the new tracer.

Background: The aim of this study was to evaluate the value of attenuation correction of technetium 99m tetrofosmin single photon emission computed tomography (SPECT) imaging for the detection of myocardial viability., Methods and Results: A head-to-head comparison between resting Tc-99m tetrofosmin SPECT and fluorine 18 fluorodeoxyglucose (FDG) SPECT was performed. Both the noncorrected and attenuation-corrected Tc-99m tetrofosmin SPECT images were compared with the FDG images that served as the reference for viability. Consecutive patients (n = 33) with chronic coronary artery disease and left ventricular dysfunction were included. Segmental Tc-99m tetrofosmin and FDG data were displayed in polar maps (17-segment model), and the segments were normalized to peak activity by use of the 4D-MSPECT software program. Segments with normalized FDG activity greater than 50% were considered viable. A similar cutoff value to assess viability was used for the noncorrected and attenuation-corrected Tc-99m tetrofosmin images. Regional contractile function was determined from the gated Tc-99m tetrofosmin images and scored as normokinesia, hypokinesia, or akinesia/dyskinesia. Of all segments, 482 (85%) were viable on FDG SPECT. Of these, 427 (89%) were classified as viable with noncorrected Tc-99m tetrofosmin. Thus 55 (11%) were underestimated with noncorrected Tc-99m tetrofosmin SPECT; these segments were mainly located in the inferior and inferoseptal regions. Attenuation correction changed the classification of 39 (70%) of the underestimated segments to viable. By use of attenuation correction, the agreement between Tc-99m tetrofosmin and FDG imaging improved from 84% to 90%. Similar observations were made when the analysis was restricted to the dysfunctional segments., Conclusion: The addition of attenuation correction to Tc-99m tetrofosmin SPECT significantly improved detection of myocardial viability in patients with chronic coronary artery disease, although minimal underestimation of viability remained as compared with FDG SPECT imaging.

Sentinel node detection in patients with breast cancer is routinely performed in our department. Images frequently show star-shaped activity at the site of injection caused by septum penetration. These star-shaped artifacts could possibly impair visualization of nearby sentinel nodes. The aim of this study was to determine whether sentinel node detection in patients with breast cancer can be improved using a medium-energy all-purpose (ME) collimator instead of a low-energy all-purpose (LEAP) collimator. For this purpose, 15 patients were studied and a phantom study was performed. The LEAP collimator was used for a dynamic study immediately after injection, and both the LEAP and the ME collimators were used for static studies. A total of 20 sentinel nodes were found with both collimators. All sentinel nodes were found in the axilla. To separate sentinel nodes from the injection site, the ME collimator gave the best results in 4 of 15 patients, but only within the first hour after injection. To separate 2 nearby sentinel nodes from each other, the LEAP collimator gave the best results in 3 of 15 patients. Our conclusion is that the LEAP collimator gave better results than the ME collimator as a result of the better resolution and the higher sensitivity. Use of the ME collimator did not improve sentinel node detection.

Unlabelled: The objective of this study was to compare 18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) PET with clinical TNM staging, including that by 18F-FDG PET, in patients with non-small cell lung cancer (NSCLC)., Methods: Patients with NSCLC underwent whole-body 18F-FDG PET and whole-body 18F-FLT PET, using a median of 360 MBq of 18F-FDG (range, 160-500 MBq) and a median of 210 MBq of 18F-FLT (range, 130-420 MBq). 18F-FDG PET was performed 90 min after 18F-FDG injection, and 18F-FLT PET was performed 60 min after 18F-FLT injection. Two viewers independently categorized the localization and intensity of tracer uptake for all lesions. All 18F-FDG PET and 18F-FLT PET lesions were compared. Staging with 18F-FLT PET was compared with clinical TNM staging based on the findings of history, physical examination, bronchoscopy, CT, and 18F-FDG PET. From 8 patients, standardized uptake values (SUVs) were calculated. Maximal SUV and mean SUV were calculated., Results: Sixteen patients with stage IB-IV NSCLC and 1 patient with strong suspicion of NSCLC were investigated. Sensitivity on a lesion-by-lesion basis was 80% for the 8 patients who received treatment before 18F-FLT PET and 27% for the 9 patients who did not receive pretreatment, using 18F-FDG PET as the reference standard. Compared with clinical TNM staging, staging by 18F-FLT PET was correct for 8 of 17 patients: 5 of 9 patients in the group with previous therapy and 3 of 8 patients in the group without previous therapy. The maximal SUV of 18F-FLT PET, at a median of 2.7 and range of 0.8-4.5, was significantly lower than that of 18F-FDG PET, which had a median of 8.0 and range of 3.7-18.8 (n = 8; P = 0.012). The mean SUV of 18F-FLT PET, at a median of 2.7 and range of 1.4-3.3, was significantly lower than that of 18F-FDG PET, which had a median of 6.2 and range of 2.8-13.9 (n = 6; P = 0.027)., Conclusion: 18F-FLT PET is not useful for staging and restaging NSCLC.

Trastuzumab (Herceptin) is a recombinant humanised IgG1 monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), used for metastatic breast cancer treatment. Radiolabelled trastuzumab may have several future applications for diagnostic use. The aim of the present study was to develop clinical grade (111)Indium ((111)In) radiolabelled trastuzumab, to evaluate the stability and immunoreactivity of the tracer and to perform a biodistribution study in human tumour-bearing mice. Trastuzumab was radiolabelled with (111)In using DTPA as a chelator. (111)In-DTPA-trastuzumab (labelling yield 92.3+/-2.3%, radiochemical purity 97.0+/-1.5%) is stable in PBS when stored at 4 degrees C for more than 14 days. The immunoreactive fraction determined by cell-binding assays, using the HER2-overexpressing human ovarian SK-OV-3 tumour cell line, was 0.87+/-0.06. Biodistribution and tumour targeting were studied in HER2 receptor-positive and -negative tumour-bearing athymic mice. The HER2-positive tumour showed (9.77+/-1.14% injected dose per gram (ID g(-1))) substantial uptake of the labelled antibody already after 5 h. The difference in uptake between HER2-positive versus -negative tumours was even more pronounced 3 days after injection (16.30+/-0.64% ID g(-1)), and was visualised by radioimmunoscintigraphy. Liver, spleen and kidney showed marked tracer uptake. In summary, trastuzumab can be efficiently radiolabelled with (111)In with high labelling yields and high stability. (111)In-DTPA-trastuzumab selectively binds to the human HER2 receptor both in vitro and in vivo in animals. Therefore, (111)In-DTPA-trastuzumab appears suitable for clinical use.

Unlabelled: The purpose of this study was to appraise the value of PET in the assessment of the effect of supposedly proangiogenic new therapies such as gene therapy with vascular endothelial growth factor (VEGF) gene and endomyocardial laser therapy., Methods: Thirty-five patients with end-stage coronary artery disease and class III (Canadian Cardiovascular Society) angina were included. Myocardial ischemia was evaluated with dipyridamole PET scanning and exercise tolerance with bicycle ergometry. Ten patients were treated with naked plasmid DNA encoding for human VEGF165 (VEGF) and 12 patients were treated with laser therapy (direct myocardial revascularization [DMR]) using an electromechanical mapping system. Thirteen patients were treated with standard medical therapy (control)., Results: In both active treatment groups, angina was reduced in most subjects, except in 2 VEGF and 5 DMR patients. In the control group, no improvement in anginal classification was found, except in 3 subjects. On the PET scan, solely in the VEGF group, the stress perfusion was significantly improved (from 57 +/- 33 to 81 +/- 55 mL/min/100 g; P = 0.031). Furthermore, in the VEGF group, the number of ischemic segments was reduced from 274 +/- 41 to 234 +/- 48 segments (P = 0.004) but not in the DMR group (from 209 +/- 43 to 215 +/- 52 segments) or in the control group (from 218 +/- 18 to 213 +/- 28 segments). Bicycle exercise duration showed slight nonsignificant changes in the VEGF group (from 3.6 +/- 2.0 to 4.6 +/- 2.1 min), in the DMR group (from 5.1 +/- 1.5 to 4.7 +/- 1.3 min), and in the control group (from 3.3 +/- 1.8 to 3.5 +/- 2.3 min)., Conclusion: PET showed that intramyocardial gene therapy with the human VEGF165 gene in contrast to laser DMR treatment effectively reduces myocardial ischemia.

Unlabelled: Sentinel lymph node biopsy (SLNB) without further axillary dissection in patients with sentinel node-negative breast carcinoma appears to be a safe procedure to ensure locoregional control. During a median follow-up of 35 months the false-negative rate was 1% in our study population of 185 patients., Background: The objective of this prospective study is to provide data on follow-up of patients with primary operable breast carcinoma staged with SLNB without axillary lymph node dissection (ALND) if the sentinel lymph nodes (SLNs) were tumour-negative., Methods: One hundred and eighty-five patients were enrolled. Preoperative dynamic and static lymphoscintigraphy were performed; both a vital blue dye and a gamma detection probe were used intraoperatively. Patients with tumour-positive SLNs received completion ALND or if no SLNs could be identified. All patients were monitored according to regional follow-up protocols., Results: The SLNs were identified in 179 out of the 185 patients. In 73 patients the SLNs were tumour-positive and in 106 patients tumour-negative. The median follow-up was 35 months (range 17-59). In one SLN-negative patient an axillary recurrence occurred 26 months after the SLNB (false-negative rate: 1%)., Conclusions: SLNB without ALND appears to be a safe procedure to ensure locoregional control in SLN-negative breast carcinoma, if carried out by an experienced team.

Background: Conventional imaging such as with (99m)Tc(V)dimercaptosunnic acid (DMSA), (111)In-octreotide scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI) rarely localizes occult medullary thyroid cancer (MTC). The role of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is not well defined. The aim of this study was to examine the usefulness of postoperative FDG-PET in localizing MTC metastases., Methods: FDG-PET was performed in 26 patients with elevated serum tumor markers after total thyroidectomy with central compartment dissection and additional neck dissection on indication. Patient- and lesion-based results were compared with the findings of conventional nuclear imaging and validated by morphological imaging (CT, MRI, ultrasonography), including bone scintigraphy and pathology when possible. Clinical impact was evaluated., Results: FDG-PET detected foci in 50% of patients with lesion-based sensitivity of 96%. (111)In-octreotide detected foci in 19% with sensitivity of 41%, and (99m)Tc(V)DMSA scintigraphy and morphological imaging detected foci in 21% and 40%, respectively, with sensitivity of 57% and 87%. No lesions were found in 11 patients (42%). Positive FDG-PET findings led to surgical intervention in nine patients (35%). They all underwent surgery for removal of residual tumor or metastases. One patient achieved disease-free status. In all patients who underwent surgery, serum calcitonin levels were reduced by an average of 58 +/- 31%., Conclusions: For detection of occult MTC lesions, FDG-PET is superior to conventional nuclear imaging and is the best detection method yet available. FDG-PET in postoperative follow-up has clinical value and may be used for guiding reoperation and additional morphological imaging preoperatively.

Objectives: There is an increasing interest among gynecologic oncologists to implement the sentinel lymph node (SLN) procedure in vulvar cancer patients in clinical practice. However, the safety of this promising method of staging still has to be proven in a randomized trial., Materials and Methods: Two vulvar cancer patients are reported to illustrate pitfalls in the sentinel lymph node procedure., Results: The phenomena of bypassing the sentinel lymph node and confusion about the number of removed sentinel lymph nodes are presented and discussed., Conclusion: Gynecological oncologists who perform the sentinel lymph node procedure in vulvar cancer patients should perform this technique by following a strict protocol and within the protection of a clinical trial.

Unlabelled: Standard staging of esophageal and gastroesophageal junction (GEJ) tumors substantially lacks accuracy. The aim of this study was to investigate whether the addition of PET with (18)F-FDG is a valuable gain in the initial staging., Methods: Between January 1996 and January 2002, (18)F-FDG PET was performed in 74 patients. Conventional staging included CT in all patients and well-performed endoscopic ultrasonography (EUS) in 52 patients. They were compared with (18)F-FDG PET with pathology and follow-up of suspicious lesions as the gold standard., Results: PET identified 70 primary tumors (sensitivity, 95%). Sensitivity to identify locoregional metastases was highest for EUS (69%) but was not different for CT and PET (44% and 55%, respectively). PET was able to identify distant nodal disease in 71% (17/24 patients) compared with 29% (7/24 patients) after combined CT/EUS alone (P = 0.021). Sensitivity to detect distant nodal and systemic (M1) disease increased with PET (78% vs. 37%; P = 0.012). PET upstaged 15 patients (15/74; 20%) correctly as M1 disease, missed by CT/EUS, and correctly downstaged 4 patients (5%) from M1 to M0 disease. However, false upstaging and downstaging was encountered in 5 (7%) and 3 (4%) patients, respectively., Conclusion: PET improves the currently applied staging of esophageal and GEJ tumors, particularly by ameliorating the detection of M1 disease.

Background: The new anti-cancer drug imatinib mesylate inhibits the tyrosine kinase growth factor receptor, c-KIT, and has shown spectacular activity in patients with gastrointestinal stromal tumours (GISTs)., Objective: To assess whether fluorodeoxyglucose positron emission tomography (FDG PET) is suitable for response evaluation of this new type of tumour treatment., Methods: Sixteen consecutive patients with irresectable or metastasized GIST or another c-KIT (CD117) positive mesenchymal tumour underwent FDG PET before and 1 week after the start of treatment with imatinib mesylate (Glivec). Visual findings and standard uptake values (SUVs) were compared with the overall response to treatment, based on clinical and radiological response., Results: PET visualized all known and some unknown tumour locations. The separation by PET after 1 week of treatment in "PET responders" (11/16 patients, mean SUV reduction 65%) versus "PET non-responders" (5/16 patients, mean SUV increase 16%) appeared to match almost perfectly with overall treatment response and proved correct in 14/15 patients (prediction sensitivity 93%). FDG uptake changes after 1 week of treatment were of greater magnitude than tumour volume changes on computed tomography at 8 weeks. Progression-free survival was significantly better in patients with a PET response (P=0.002). PET response predicted treatment outcome better than the radiological response. Finally, PET was helpful during follow-up, in discriminating side effects from tumour progression., Conclusion: FDG PET is a valuable tool in patients with gastrointestinal stromal tumours treated with imatinib mesylate. It improves staging, accurately separates responders from non-responders in an early phase, and is helpful during follow-up.

Amyloidosis is a group of diseases, all characterised by deposition of protein fibrils with a beta-sheet structure. This structure generates affinity of amyloid for Congo red dye and is resistant to proteolysis. Three types of systemic amyloidosis are important for the clinician: AA (related to underlying chronic inflammation), AL (related to underlying monoclonal light chain production) and ATTR amyloidosis (related to old age or underlying hereditary mutations of transthyretin). Signs and symptoms vary considerably among the three types and the choice of treatment differs completely. A stepwise approach in diagnosis and therapy is presented. When amyloidosis is suspected the first step is histological proof of amyloid and the second is proof of systemic involvement. The next two steps are determination of the type of amyloid followed by detection of the precursor protein. The fifth step is a thoughtful clinical evaluation, necessary for assessment of prognosis and therapy. Subsequently, the choice of therapy is based on the 'precursor-product' concept. In the final step, the effects of therapy on the underlying disease as well as on the amyloidosis are assessed during follow-up. In this evaluation serum amyloid P component (SAP) scintigraphy helps to show organ involvement and therapy response.

Unlabelled: Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology. It has been suggested that radiolabeled nucleosides might be more tumor specific., Methods: To test this hypothesis, we compared the biodistribution of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) and (18)F-FDG in Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus (30 MBq) of either (18)F-FLT (n = 5) or (18)F-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of (18)F-FLT proved to be necessary to reduce the serum levels of endogenous thymidine and achieve satisfactory tumor uptake of radioactivity., Results: Tumor-to-muscle ratios of (18)F-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of (18)F-FLT (3.8 +/- 1.3). (18)F-FDG showed high physiologic uptake in brain and heart, whereas (18)F-FLT was avidly taken up by bone marrow. (18)F-FDG accumulated in the inflamed muscle, with 4.8 +/- 1.2 times higher uptake in the affected thigh than in the contralateral healthy thigh, in contrast to (18)F-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4)., Conclusion: In (18)F-FDG PET images, both tumor and inflammation were visible, but (18)F-FLT PET showed only the tumor. Thus, the hypothesis that (18)F-FLT has a higher tumor specificity was confirmed in our animal model.

Purpose: The aim of the study was to investigate the feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine positron emission tomography (FLT-PET) for the detection and grading of soft tissue sarcoma (STS)., Experimental Design: Nineteen patients with 20 STSs of the extremities were scanned, using attenuation corrected whole-body FLT-PET. Standardized uptake values (SUVs) and tumor:nontumor ratios (TNTs) were compared with histopathological parameters using French and Japanese grading systems., Results: Mean SUV, maximal SUV, and TNT could differentiate between low-grade (grade 1; n = 6) STS and high-grade (grade 2 and 3; n = 14) STS according to the French grading system (P = 0.001). Mean SUV, max SUV, and TNT correlated with mitotic score, MIB-1 score, the French and Japanese grading system (* = 0.550-0.747)., Conclusions: FLT-PET is able to visualize STS and differentiate between low-grade and high-grade STS. The uptake of FLT correlates with the proliferation of STS.

Unlabelled: The aim of this study was to compare left ventricular (LV) volumes and regional wall motion determined by PET with those determined by the reference technique, cardiovascular MRI., Methods: LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were measured and regional wall motion was scored in 38 patients with chronic coronary artery disease by both gated (18)F-FDG PET and MRI. A 9-segment model was used for PET and MRI to assess regional wall motion., Results: Good correlations were observed between MRI and gated PET for all parameters (r values ranging from 0.91 to 0.96). With PET, there was a significant but small underestimation of LVEDV and LVEF. Mean +/- SD LVEDV, LVESV, and LVEF for MRI were 131 +/- 57 mL, 91 +/- 12 mL, and 33% +/- 12%, respectively, and those for gated PET were 117 +/- 56 mL, 85 +/- 51 mL, and 30% +/- 11%, respectively. For regional wall motion, an agreement of 85% was found, with a kappa-statistic of 0.79 (95% confidence interval, 0.70-0.89; SE, 0.049)., Conclusion: LV volumes, LVEF, and regional wall motion can be assessed with gated (18)F-FDG PET and correlate well with these parameters assessed by MRI.

Background: Sarcomas represent a significant diagnostic and therapeutic challenge that requires techniques to provide better assessment of the disease than provided by traditional means. FDG-PET depicts the increased metabolism in abnormal tissues, enabling visualisation and quantification in vivo. The objective of this review was to assess the diagnostic value of FDG-PET in the detection, grading and therapy response of soft tissue and bone sarcomas., Methods: A systematic review and meta-analysis of clinical studies on FDG-PET and sarcomas was conducted. Databases of PubMed, Embase and Cochrane were searched for studies. Besides that, the references of identified studies were reviewed. Three reviewers independently assessed the methodological quality. Statistical pooling was possible for studies concerning detection and grading of studies with mixed sarcomas (soft tissue and bone) and studies with soft tissue sarcomas only., Results: Twenty-nine studies met the inclusion criteria. There was disagreement between the reviewers in 21.5% of the questions from the criteria list. The methodological quality of most of the included studies was poor. Pooled sensitivity, specificity and accuracy of PET for the detection of sarcomas were 0.91, 0.85 and 0.88, respectively. The difference between the mean Standard Uptake Value (SUV) in malignant and benign tumours for the studies concerning mixed and soft tissue sarcomas was statistically significant, as well as the difference in FDG uptake between low and high grade mixed sarcomas., Conclusions: The meta-analysis in this study was limited by the fact that only a few studies had mutual comparable outcome parameters. Moreover, the methodological quality of the studies was generally poor. Nevertheless, our results indicate that FDG-PET can discriminate between sarcomas and benign tumours and low and high grade sarcomas based on the mean SUV. The diagnostic implications of these results have to be investigated, especially the discrimination between benign tumours and low grade sarcomas. Based on this meta-analysis, there is no indication to use FDG-PET in the standard treatment of sarcomas. In the future PET imaging in bone and soft tissue sarcomas should be directed to the clinical implication for the detection and grading of sarcomas and the treatment evaluation of locally advanced sarcomas.

Unlabelled: The feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with (18)F-FDG PET., Methods: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary laryngeal cancer underwent attenuation-corrected (18)F-FLT PET imaging 60 min after injection of a median of 213 MBq (range, 175-400 MBq) (18)F-FLT and attenuation-corrected (18)F-FDG PET imaging 90 min after injection of a median of 340 MBq (range, 165-650 MBq) (18)F-FDG. All patients were staged by endoscopy and CT according to the Union Internationale Contre la Cancer TNM staging system. All patients underwent biopsy of the laryngeal area after imaging. Lesions seen on (18)F-FDG PET and (18)F-FLT PET were compared with histopathologic results. Mean SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for (18)F-FLT and (18)F-FDG. Wilcoxon nonparametric testing was used for comparison of (18)F-FDG with (18)F-FLT uptake. The Spearman correlation coefficient was used to correlate mean SUVs, maximum SUVs, and TNT ratios of (18)F-FDG PET and (18)F-FLT PET. Two-tailed P values < 0.05 were considered significant., Results: (18)F-FDG PET and (18)F-FLT PET detected laryngeal cancer correctly in 15 of 17 patients. One lesion judged as positive on (18)F-FDG PET turned out to be normal tissue. Of 2 lesions judged as positive on (18)F-FLT PET, 1 turned out to be inflammation and the other to be normal tissue. Maximum SUVs were 3.3 (range, 1.9-8.5) for (18)F-FDG and 1.6 (range, 1.0-5.7) for (18)F-FLT (P < 0.001). Mean SUVs were 2.7 (range, 1.5-6.5) for (18)F-FDG and 1.2 (range, 0.8-3.8) for (18)F-FLT (P < 0.001). TNT was 1.9 (range, 1.3-4.7) for (18)F-FDG and 1.5 (range, 1.1-3.5) for (18)F-FLT (P < 0.05)., Conclusion: The numbers of laryngeal cancers detected with (18)F-FLT PET and (18)F-FDG PET were equal. In laryngeal cancer, the uptake of (18)F-FDG is higher than that of (18)F-FLT.

Objectives: To determine the value of Positron Emission Tomography (PET) in the diagnosis of Takayasu arteritis (TA) and giant cell arteritis (GCA) and its value in the assessment of disease activity and response to therapy., Methods: In 5 consecutive patients diagnosed with TA or GCA, PET using the tracer F18-deoxyglucose (FDG) was performed when disease activity was suspected based on clinical and laboratory parameters. PET was repeated after therapeutic intervention when disease remission was achieved. PET findings were compared with angiography, MRA and clinical parameters., Results: PET visualised inflamed arteries in all 5 patients, but there was a discrepancy between PET and angiography or MRA. In 8 arteries of 4 patients only PET showed disease involvement, while in 5 arteries of 2 patients only angiography or MRA showed involvement. After treatment and the disappearance of clinical symptoms, FDG uptake was clearly reduced compared to the initial scan in all patients. In all but one the acute phase response declined. In that patient a urinary tract infection explained the elevated acute phase response, as this normalised after antibiotic treatment., Conclusion: PET is a promising new technique for the diagnosis of large vessel vasculitides. Furthermore, PET appears to be a valuable tool for the assessment of disease activity during follow-up and of the response to therapy.

Planar gated blood-pool imaging (GBPI) is a standard method for non-invasive assessment of left ventricular (LV) function. Gated blood-pool single photon emission computed tomographic (GBPS) data acquisition can be accomplished in the same time as GBPI, with the benefit of enabling visualization of all cardiac chambers simultaneously. The purpose of this investigation was to evaluate the degree to which automated and manual LVEF calculations agree with one another and with conventional GBPI LVEF measurements. GBPI studies were performed in 22 consecutive, unselected patients, followed by GBPS data acquisition. GBPS left ventricular ejection fraction (LVEF) calculations were performed by available software (NuSMUGA, Northwestern University, Chicago, IL) automatically and manually, using all LV gated short axis slices. Automatic LVEF assessed by GBPS correlated well with conventional planar GBPI (r = 0.88, P < 0.001). Mean planar GBPI LVEF was 50% +/- 12%, and mean GBPS automatic LVEF was significantly lower at 45% + 14% (P = 0.001), with a mean difference of 6% +/- 5%. Manual GBPS LVEF also correlated well with conventional planar GBPI (r = 0.90, P < 0.0001). Mean LVEF measurement by manual GBPS versus GBPI was significantly higher at 59% +/- 13%, with a mean difference of 10% +/- 6% (P < 0.001). Manual GBPS LVEF values were also significantly higher than automatically determined GBPS LVEF values (P < 0.001). It is concluded that LVEF values assessed by NuSMUGA GBPS software were reproducible, and automatic and manual values correlated well with conventional GBPI values. However, both automatic and manual GBPS calculations were significantly different from one another and from GBPI values, so that GBPI and NuSMUGA calculations cannot be considered to be equivalent.

Unlabelled: In this study, the feasibility of 3'-(18)F-fluoro-3'-deoxy-L-thymidine PET ((18)F-FLT PET) for staging patients with clinical stage III melanoma was investigated., Methods: Ten patients with melanoma and metastases to the locoregional draining lymph nodes, clinical stage III-based on physical examination, chest radiography, lactate dehydrogenase, and histopathologic confirmation-underwent a whole-body (18)F-FLT PET scan 1 h after injection of a median 400-MBq dose (range, 185-430 MBq) of (18)F-FLT. All (18)F-FLT PET lesions were verified using the American Joint Committee on Cancer Staging System, which includes physical examination, spiral CT, ultrasound, chest radiography, and histopathologic examinations. Size and mitotic rate of metastatic lymph nodes and skin metastases were determined., Results: All histopathologic samples and (18)F-FLT PET lesions were categorized over anatomic regions and correlated. All locoregional metastases were correctly visualized by (18)F-FLT PET. Region-based sensitivity for detection of lymph node metastatic disease was 88%. There were 3 true-negative and 2 false-positive lesions. The detection limit for lymph node metastases appeared to be approximately 6 mm or a mitotic rate of 9 mitoses per 2 mm(2). Two patients were upstaged by (18)F-FLT PET, which was confirmed by CT. In 3 patients, (18)F-FLT PET detected a total of 3 additional lesions with therapeutic consequences, without influencing staging. These lesions were initially missed by clinical staging., Conclusion: (18)F-FLT PET seems promising for (re)staging purposes in clinical stage III melanoma. Further research is needed, in which (18)F-FLT PET should be compared with (18)F-FDG PET.

The aim of this study was to determine the yield of attenuation correction in myocardial perfusion imaging (MPI), before and after a 1-year experience period. In 48 consecutive patients referred for MPI, both non-corrected (NC) and attenuation-corrected (AC) images were analysed by three independent readers shortly after implementation of attenuation correction. The same images were re-analysed 1 year later, after having obtained experience in attenuation correction on a routine basis in >500 patients with clinical feedback. Results were compared with gold standards for ischaemia and infarction based on coronary angiography, follow-up, ultrasound and gated blood pool imaging. Sensitivity and specificity for the detection of coronary artery disease were 95% and 45% respectively for NC images and 77% and 70% respectively for AC images at first readings. After 1 year of AC experience, NC sensitivity/specificity was 100%/61%, and AC results were 89%/92%. It is concluded that attenuation correction improves the performance of MPI interpretation. With attenuation correction, specificity is increased and sensitivity is similar as compared with NC images. However, attenuation correction requires experience and is associated with a learning curve.

Background: 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) is valuable in staging of esophageal cancer. However, FDG-PET may falsely upstage patients leading to incorrect exclusion from surgical treatment. This study was performed to determine the false-positive rate and possible causes., Methods: The rate of false-positive lesions on FDG-PET was documented in 86 out of a group of 98 patients. Lesions were defined as false positive when pathological examination was negative or as absence of tumor activity within 6 months of follow-up. To evaluate the influence of a learning curve on the false-positive rate, the PET scans were revised recently., Results: False-positive lesions were found in 13 patients (13 of 86; 15%). FDG-PET incorrectly revealed only locoregional node metastases in 5 patients in whom surgery with curative intent was performed. Ten lesions in the other 8 patients were classified as distant organ or as nonregional node metastases (M1a/1b). Finally, 5 patients upstaged to M1a/1b underwent a curative resection. The number of false-positive lesions decreased from 16 to 5 (6%) after revision., Conclusions: Proper interpretation of FDG-PET in staging esophageal cancer is impeded by false-positive results. Even after completion of the learning curve, positive FDG-PET findings still have to be confirmed by additional investigations.

Background: In comparison with planar imaging gated blood-pool single photon emission computed tomography (GBPS) has the advantage of separating left and right ventricle. The purpose of this investigation was to evaluate the right ventricular ejection fraction (RVEF) calculations by GBPS software ('NuSMUGA', Northwestern University, Chicago, IL) in comparison to first-pass radionuclide angiography (FPRNA)., Methods: In 22 consecutive patients FPRNA and GBPS acquisition was performed. GBPS RVEF calculations were manually and automatically performed, using all gated short-axis-slices of the right ventricle., Results: Automatic RVEF assessed by GBPS did not correlate with conventional FPRNA (r = 0.40, p = 0.065). Mean FPRNA RVEF was 55 +/- 10% and mean GBPS automatic RVEF was 32 +/- 8%. Also manual GBPS RVEF did not correlate with conventional FPRNA (r = 0.41, p = 0.055). Mean RVEF measurement by manual GBPS was 33 +/- 8%. Manual GBPS RVEF values correlated well with automatically determined GBPS RVEF values (r = 0.96, p < 0.0001)., Conclusion: Automatic and manual values RVEF values assessed by GBPS did not correlate with conventional FPRNA values. FPRNA and GBPS calculations cannot be considered to be equivalent. Therefore the NuSMUGA program cannot be used to calculate RVEF.

Background: Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear., Objective: To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions., Methods: Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity., Results: WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections., Conclusion: Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower.

Background: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative (131)I diagnostic whole-body scan (WBS) is advocated. However, the therapeutic benefit of this "blind" treatment is not clear., Objective: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic (131)I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose (131)I., Design: Retrospective single-center study., Methods: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi (131)I. Median follow-up from this treatment until the end of observation was 4.2 Years (range 0.5-13.5 Years)., Results: The post-treatment WBS revealed (131)I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive post-treatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P=0.001)., Conclusions: High-dose iodine treatment in diagnostically negative patients who have a negative post-treatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

Unlabelled: The purpose of this study was to describe the clinical presentation of bone metastases in patients with carcinoid tumors and to determine the diagnostic value of imaging techniques and markers of bone metabolism., Methods: This retrospective study was performed on the entire group of patients with carcinoid tumors treated in our hospital from January 1992 to May 1999. Only patients with metastasized tumors were included., Results: Eleven of 90 patients (12%) (95% confidence interval [CI], 5%-19%) with a metastasized carcinoid tumor had symptomatic bone metastases. All bone metastases occurred in 55 patients with midgut carcinoids (20%; 95% CI, 9%-31%). Plain radiography had a sensitivity of 44% (95% CI, 12%-76%); MRI, 100% (95% CI, 61%-100%); bone scintigraphy, 90% (95% CI, 72%-100%); and octreotide scintigraphy, 60% (95% CI, 35%-93%). In 9 patients, both octreotide scintigraphy and bone scintigraphy were performed. Of 45 bone lesions, 22 (49%) were visualized by both modalities, 13 (29%) were visualized with octreotide scintigraphy but not with bone scintigraphy, and 10 (22%) were visualized with bone scintigraphy but not with octreotide scintigraphy. In 2 patients, octreotide scintigraphy and bone scintigraphy provided complementary results. Markers of bone metabolism could not discriminate carcinoid patients from those without bone metastases. The markers of bone metabolism did not reflect the osteolytic or osteoblastic appearance of metastases., Conclusion: Pain is the principal symptom of bone metastases in patients with carcinoid tumors. Plain radiography and markers of bone metabolism do not contribute to the diagnosis of bone metastases. MRI has a high sensitivity for bone metastases. Both bone scintigraphy and octreotide scintigraphy have acceptable sensitivity and can provide complementary results.

The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research, new diagnostic techniques, such as Positron Emission Tomography and the introduction of the sentinel lymph node biopsy with advanced laboratory methods such as immuno-histochemical markers, and reverse transcriptase polymerase chain reaction, have been developed to facilitate early detection of metastatic melanoma. The role of these new techniques on the staging and surgical treatment of melanoma is discussed in this paper.

Aim: The aim of this study was to evaluate the reliability and clinical impact of sentinel node biopsy, including preoperative lymphoscintigraphy and intraoperative lymphatic mapping in patients with cutaneous melanoma of the head, neck, trunk or extremities., Methods: Two hundred patients (103 women, 97 men), median age 57 (range 21-86) years with cutaneous melanoma > or =1.0mm Breslow thickness and clinically negative lymph nodes participated in a single institutional prospective study from May 1995 to January 2000. Primary melanoma sites included: 22 head and neck (11%), 67 trunk (34%), 29 upper extremity (14%) and 82 lower extremity (41%). The median Breslow thickness was 2.5 (range 1.0-20.0)mm. Preoperative dynamic and static lymphoscintigraphy, intraoperative blue dye and a gamma detection probe were used. If histological examination with HE or IHC showed metastases, therapeutic lymph node dissection (TLND) was performed., Results: Sentinel node(s) could be identified in 197 patients (99%); 393 sentinel nodes (mean: 2.0 per patient, range 1-7) were removed from 241 basins. Three procedures failed in the head and neck region. In 167 patients, the sentinel nodes were both blue and radioactive (85%); in 26 patients, they were only radioactive (13%) and in four patients only blue (2%). In total, 150 patients had tumour-negative sentinel nodes (76%). During a median follow-up of 47 (range 24-79) months, nodal recurrence in a negative mapped basin was documented in six patients of which isolated recurrence was in two patients and recurrence together with locoregional recurrence in four patients (false negative rate 6/54=11%). Estimated three-year recurrence-free survival in the node-negative patients and node-positive patients was 83 and 66% respectively (P<0.05). The overall survival at three years was 92 and 73% respectively (P<0.05)., Conclusion: Sentinel node biopsy provides accurate staging and important prognostic information. The final place of sentinel node biopsy is still undefined, and therefore sentinel node biopsy is still considered as an experimental surgical staging procedure.