Imaging of infectious diseases using [18F] fluorodeoxyglucose PET.

The role of fluorodeoxyglucose positron emission tomography (FDG PET) in the diagnostic localization of infectious diseases has expanded rapidly in years. In general, sensitivity of FDG PET in depicting infections compares favorably to other diagnostic modalities . It is shown to be useful in patients with suspected osteomyelitis, especially in chronic low grade infections and in vertebral osteomyelitis. although the sensitivity of FDG PET in prosthetic joint infections is very high, reported specificity varies considerably. In experienced centers, FDG uptake localized along the interface between bone and prosthesis can be used to diagnose infection with acceptable specificity. Combined leukocyte scintigraphy and bone scanning, however, remains the standard scintigraphic method for diagnosis of infected joint prostheses. FDG PET has shown promising results in vascular graft infections, in the evaluation of metastatic infectious foci inpatients with blood stream infections and in neutropenic patients, but further studies are needed before definitive conclusions can be drawn . In fever of unknown origin (FUO), FDG PET appears to be of great advantage as malignancy, inflammation and infection can be detected. Image fusion combining PET and computed tomography facilitates anatomical localization of increased FDG uptake and better guiding for further diagnostic tests to achieve a final diagnosis. In conclusion, the body of evidence on utility of FDG PET in infectious diseases and FUO is growing and FDG PET may become one of the preferred diagnostic procedures for many of these diseases, especially when a definite diagnosis cannot easily be achieved.

Chemotherapy response evaluation with FDG-PET in patients with colorectal cancer.

BACKGROUND: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. METHODS: Dynamic FDG-PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates. RESULTS: There was an increase in the rates of death (P = 0.049 for DeltaMRGlu PET1-2; P = 0.017 for DeltaSUV PET1-2; P = 0.032 for DeltaMRGlu PET1-3; P = 0.048 for DeltaSUV PET1-3) and progression (P = 0.026 for DeltaMRGlu PET1-2; P = 0.035 for DeltaSUV PET1-2; P = 0.041 for DeltaMRGlu PET1-3; P = 0.081 for DeltaSUV PET1-3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of DeltaMRGlu and DeltaSUV cut-off levels. CONCLUSION: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG-PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.

Iron absorption during epoetin alfa therapy for chemotherapy-associated anaemia.

Absorption of a physiological dose of ferrous iron was studied in 18 patients with solid malignancy receiving epoetin therapy for mild chemotherapy-associated anemia. The historical control group consisted of 25 iron replete volunteers (iron absorption 20 +/- 11% in males and 26 +/- 13% in females) and 21 patients with uncomplicated iron deficiency (iron absorption 71 +/- 19%). Iron absorption was increased in the majority of the cancer patients (iron absorption 59 +/- 35%). There were no significant differences in iron absorption between cancer patients who were iron replete or iron deficient according to current clinical practice guidelines (iron deficiency: transferrin saturation < 20% and/or serum ferritin < 100 ng/mL). Red cell iron incorporation was not disturbed in the majority (89%) of patients.

FDG-PET for imaging of non-osseous infection and inflammation.

UNLABELLED: FDG-PET is emerging as a promising imaging technique in non-osseous infectious and inflammatory diseases, as an increasing number of reports are appearing in literature. In general, sensitivity of FDG-PET in diagnosing non-osseous infections compares favorably to other diagnostic modalities. Lower specificity due to FDG accumulation in conditions involving leukocyte activation and malignancy may be overcome by implementing FDG-PET in a diagnostic protocol. In fever of unknown origin, FDG-PET appears to be of great advantage as malignancy, inflammation and infection can be detected. Studies on standardized uptake value ratios, uptake patterns and dynamics may be helpful to increase specificity. Image fusion combining PET and CT facilitates anatomical localization of increased FDG-uptake and better guiding for further diagnostic tests to achieve a final diagnosis. More data on the utility of FDG-PET to monitor the response to treatment will be available in near future. Early reports on FDG-PET during treatment follow-up in large vessel vasculitis already showed promising RESULTS: In conclusion, the body of evidence on the utility of FDG-PET in non-osseous infection and inflammation is growing and FDG-PET may become one of the preferred diagnostic procedures for these diseases.

Decrease of (99m)Tc-uptake in autonomous thyroid tissue in Germany since the 1970s. Clinical implications for radioiodine therapy.

AIM: The clinical relevance of thyroidal autonomy, i.e. the risk of a patient to become hyperthyroid after exposure to iodine, can be estimated by measurement of the thyroidal (99m)Tc uptake under suppression of TSH (TcTUs). The upper tolerable limit has been set to 2% some 25 years ago. Considering the increase in nutritional iodine uptake over the last 15 years, we wanted to find out if the TcTUs per ml of autonomous volume may have changed. PATIENTS, METHODS: We performed a pilot study in 1166 randomly chosen patients from 1980-2003 with different kinds of benign thyroid disorders to determine changes in TcTU or TcTUs over time. A second analysis was performed in 1063 patients from 1987-2004 with unifocal autonomy (UFA). In these patients, the volume of the autonomous tissue can be determined precisely thus allowing for exact determination of TcTUs per ml of autonomous volume. RESULTS: The pilot study demonstrated that the TcTUs or the TcTU has been falling over the last 25 years in all benign thyroid disorders (p < 0.01). The total thyroid volume has also been decreasing in all disorders. In the second analysis of UFA only, 500 from the 1063 patients fulfilled the inclusion criteria. In these patients, the TcTUs per ml of autonomous volume has fallen from an average of 0.48% to an average of 0.28%. These results are statistically significant as determined by ANOVA testing (p = 0.032). CONCLUSION: As the TcTUs in relation to autonomous volume has dropped by approximately 40% over the last 25 years, the upper limit for a normal TcTUs should be reduced to 1-1.4%, dependent on regional factors.

Diagnosis of Candida lung abscesses by 18F-fluorodeoxyglucose positron emission tomography.

In three patients with catheter-associated candidaemia, use of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) led to the diagnosis of Candida lung abscesses, which was confirmed by computed tomography and a favourable response to antifungal therapy. It was concluded that FDG-PET is a promising new imaging technique that enables early identification of sites of disseminated candidiasis, and that this technique can be used in the evaluation of therapy.

Radiolabeled compounds in diagnosis of infectious and inflammatory disease.

Nuclear medicine offers powerful noninvasive techniques for visualization of infectious and inflammatory disorders using whole body imaging enabling the determination of both localization and number of inflammatory foci. A wide variety of approaches depicting the different stages of the inflammatory response have been developed. Non-specific radiolabeled compounds, such as 67Ga-citrate and radiolabeled polyclonal human immunoglobulin accumulate in inflammatory foci due to enhanced vascular permeability. Specific accumulation of radiolabeled compounds in inflammatory lesions results from binding to activated endothelium (e.g. radiolabeled anti-E-selectin), the enhanced influx of leukocytes (e.g. radiolabeled autologous leukocytes, anti-granulocyte antibodies or cytokines), the enhanced glucose-uptake by activated leukocytes (18F-fluorodeoxyglucose) or direct binding to micro-organisms (e.g. radiolabeled ciprofloxacin or antimicrobial peptides). Scintigraphy using autologous leukocytes, labeled with 111In or 99mTc, is still considered the "gold standard" nuclear medicine technique for the imaging of infection and inflammation, but the range of radiolabeled compounds available for this indication is still expanding. Recently, positron emission tomography with 18F-fluorodeoxyglucose has been shown to delineate various infectious and inflammatory disorders with high sensitivity. New developments in peptide chemistry and in radiochemistry will result in specific agents with high specific activity. A gradual shift from non-specific, cumbersome or even hazardous approaches to more sophisticated, specific approaches is ongoing. In this review, the different approaches to scintigraphic imaging of infection and inflammation, already in use or under investigation, are discussed.

FDG-PET in staging lung cancer: how does it change the algorithm?

BACKGROUND: In patients with lung cancer, positron emission tomography (PET) using fluor-18-fluorodesoxyglucose (FDG) may be used both to detect extrathoracic metastases (ETM) and for mediastinal lymph node staging (MLS), potentially reducing the need for mediastinoscopy. We assessed the added value of FDG-PET in detecting ETM and focused on the reliability of FDG-PET and mediastinoscopy for MLS. PATIENTS AND METHODS: In 72 consecutive patients with non-small cell lung cancer, the impact of adding FDG-PET to full conventional clinical staging was prospectively analyzed. The predictive value of FDG-PET findings and tumor location for pathologic mediastinal lymph node status were assessed in a logistic regression analysis. RESULTS: Unexpected extrathoracic metastases were detected by FDG-PET in 15% of patients. In MLS overall negative and positive predictive values were 71 and 83% for FDG-PET, and 92 and 100% for mediastinoscopy. However, the negative predictive value of FDG-PET was only 17% in case of FDG-PET positive N1 nodes and/or a centrally located primary tumor, whereas it was 96% in case of FDG-PET negative N1 nodes and a non-centrally located primary tumor. CONCLUSION: By incorporating FDG-PET in clinical staging, 15% of patients with lung cancer are upstaged due to unexpected extrathoracic metastases. In case of a negative mediastinal FDG-PET, mediastinoscopy can only be omitted in the presence of a non-centrally located primary tumor and without FDG-PET positive N1 nodes.

Longitudinal study of bone mineral density in patients with Crohn's disease.

Osteoporosis is frequent in Crohn's disease. The aim of the study was to assess the rate of bone loss over time retrospectively and the influence of disease-related factors on bone loss. Twenty-nine patients (8 male), admitted for repeated bone mineral density assessments (BMD) were enrolled. BMD measured by dual energy x-ray absoptiometry was expressed in grams per square centimeter, and as sex- and age-matched Z score. The mean interval between BMD assessments was 41 months, during which period 27 patients used corticosteroids (mean dose 8.6 g) and 21 patients some form of bone protective medication. Initial Z scores at a mean age of 41 years were significantly below zero (spine -1.6 +/- 1.4; femur -1.4 +/- 1.4). Over time, no change in absolute BMD was observed accompanied by an improvement in Z scores. At the same time, an increase in body weight and a decrease in erythrocyte sedimentation rate (ESR) was observed. Multilinear regression analysis demonstrated change in ESR as independent predictor for change in femoral Z score. In conclusion, low BMD is frequent in Crohn's disease, but decline of BMD over time was not found, despite ongoing use of corticosteroids.

Radiolabeled chemotactic cytokines: new agents for scintigraphic imaging of infection and inflammation.

Several radiopharmaceuticals are currently used for diagnosis of inflammatory and infectious diseases in patients. Most inflammatory and infectious processes can be visualized with radiolabeled autologous leukocytes, currently considered to be the most appropriate radiopharmaceutical for this purpose. This agent is very well capable to delineate most inflammatory and infectious foci in a relatively short time after injection. The time-consuming and intricate labeling procedure and the handling of potentially contaminated blood, however cause that there is a great interest in the development of new radiopharmaceuticals comprising the same imaging qualities but without these disadvantages. Besides radiolabeled leukocytes several other radiopharmaceuticals, such as (67)Ga-citrate, radiolabeled anti-granulocyte antibodies and FDG are used to image infection and inflammation. These agents accumulate in infectious and inflammatory lesions in a non-specific manner or have suboptimal diagnostic characteristics. Nowadays, there is a great interest in the development of radiolabeled chemotactic and chemokinetic cytokines that accumulate and are retained in infectious and inflammatory foci by specific interaction with infiltrated inflammatory cells. In this review we describe the specific characteristics of the chemotactic and chemokinetic compounds that are currently studied as potential radiopharmaceutical to visualize infectious and inflammatory foci. The characteristics of a series of cytokines (IL-1, IL-2), chemokines (IL-8, PF-4, MCP-1, NAP-2), complement factors (C5a, C5adR), chemotactic peptides (fMLF) and other chemotactic factors (LTB4) are described. The potentials of these compounds to serve as an imaging agent are discussed.

F-18-fluorodeoxyglucose positron emission tomography in diagnosis and follow-up of patients with different types of vasculitis.

BACKGROUND: F-18-fluorodeoxyglucose (FDG) accumulates in inflammatory cells due to an increased metabolic rate. Therefore, FDG positron emission tomography (PET) represents a promising imaging technique in patients with vasculitis. The aim of this study was to assess the value of FDG PET in the diagnosis of different types of vasculitis. METHODS: The results of FDG PET performed because of suspected vasculitis or fever of unknown origin with results indicating vasculitis were reviewed. These results were compared with the final diagnosis, based on the American College of Rheumatology 1990 criteria. RESULTS: FDG PET was ordered because of suspected vasculitis in 20 patients, because of fever of unknown origin in two patients, and for follow-up of vasculitis in five patients. Fourteen patients were diagnosed with vasculitis (giant cell arteritis n = 5, polymyalgia rheumatica n = 2, polyarteritis nodosa n = 3, Takayasu n = 1, Churge-Strauss n = 1, Wegener's granulomatosis n = 1, vasculitis skin n = 1), two patients were diagnosed with fibromuscular dysplasia and one patient had media necrosis of the aorta. In five patients no diagnosis could be reached. FDG PET results were considered to be true-positive in ten patients, true-negative in 14 patients and false-negative in three patients resulting in a positive predictive value of 100% and a negative predictive value of 82%. CONCLUSIONS: FDG PET appears to be a promising new imaging technique in diagnosing and determining the extent of various forms of vasculitis. Furthermore, FDG PET may become a useful tool for evaluating the effect of treatment of vasculitis.

Efficacy of fluorine-18-deoxyglucose positron emission tomography in detecting tumor recurrence after local ablative therapy for liver metastases: a prospective study.

PURPOSE: The aims of this prospective study were to investigate the potential role of fluorine-18-deoxyglucose (FDG) positron emission tomography (PET) in determining the efficacy of the local tumor ablative process and to determine the added value of FDG-PET in the detection of tumor recurrence during follow-up. PATIENTS AND METHODS: Twenty-three patients with unresectable colorectal liver metastases were followed up after local ablative therapy consisting of a standard protocol including FDG-PET scanning, computed tomography (CT) scanning, and carcinoembryonic antigen measurements. The mean follow-up period was 16 months (range, 10 to 21 months). RESULTS: Ninety-six lesions was treated, 56 by local ablative treatment. Within 3 weeks after local ablative treatment, 51 lesions became photopenic on FDG-PET, while five lesions (in five patients) showed persistent activity on FDG-PET. In four of five FDG-PET-positive lesions, a local recurrence developed during follow-up; one FDG-PET-positive lesion turned out to be an abscess. None of the FDG-PET-negative lesions developed a local recurrence during a mean follow-up period of 16 months. During follow-up, 11 patients showed recurrence in the liver outside of the treated area. In all cases, previously negative FDG-PET scans became positive. Extrahepatic recurrence was encountered in nine patients during follow-up; FDG-PET showed all nine cases of tumor recurrence. There was one false-positive FDG-PET caused by an intra-abdominal abscess. In all patients, the time point of detection of recurrence by FDG-PET was considerably earlier than the detection by CT. CONCLUSION: FDG-PET seems to have a significant impact in measuring treatment efficacy directly after local ablative therapy. Furthermore, FDG-PET has an added value in patient follow-up because it reveals recurrences earlier than conventional diagnostic modalities.

Corticosteroid-induced osteoporosis: does it occur in patients with Crohn's disease?

OBJECTIVE: In Crohn's disease, osteoporosis is frequently found. However, the etiology of osteoporosis remains unclear. The aim of this study was to determine disease-related variables predictive for impaired bone mineral density (BMD). METHODS: A total of 91 patients with Crohn's disease who were admitted for BMD assessment were enrolled in the study. BMD was measured at the femoral neck and lumbar spine by dual energy x-ray absorptiometry (DXA). Results were expressed as T-score and as age- and sex-matched Z-score. Data were obtained by a questionnaire and from patients' medical records. Stepwise linear regression analysis was used to determine independent variables predictive for BMD. RESULTS: Mean age at BMD assessment was 41 +/- 12 yr, duration of disease 11.6 +/- 8.5 yr, and body mass index (BMI) 23.0 +/- 4.1 kg/m2. The cumulative dose of steroids used was 18.7 +/- 19.2 g. Mean Z-scores were less than zero (spine, -1.1 +/- 1.3 SD; femur, -1.1 +/- 1.2 SD; p < 0.0001). A total of 27 patients (30%) fulfilled the World Health Organization criteria for osteoporosis and 46 patients (50%) for osteopenia. Osteoporotic patients used more corticosteroids and had longer duration of disease, lower BMI, and more bowel resections than patients with normal BMD. However, in the linear regression analysis, the only significant independent predictors for BMD of the lumbar spine and femoral neck were BMI and history of bowel resections. BMI and history of resections together accounted for 28% of BMD Z-scores. CONCLUSIONS: BMI and a history of bowel resections were significant predictive variables for BMD. Despite the high dose of steroids used in this study, no detrimental effect could be demonstrated as independent predictor for osteoporosis.

131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative study.

The aims of this study were to establish the percentage of metastatic renal cell carcinoma (RCC) lesions detected by radioimmunoscintigraphy (RIS) with the chimeric monoclonal antibody 131I-cG250 versus positron emission tomography (PET) with 18F-labelled deoxyglucose ([18F]FDG), and to evaluate the use of these radionuclide imaging modalities compared with routinely used imaging techniques. Twenty patients with metastatic RCC disease were examined with [18F]FDG-PET and 131I-cG250 RIS within 1 week. Total body gamma camera images were obtained up to 120h after injection of 232MBq 131I-cG250. Total body PET scanning was performed 45-60 min after intravenous injection of 370MBq [18F]FDG. Nuclear medicine techniques were compared to routine imaging procedures. Routine imaging modalities revealed a total of 79 metastases. [18F]FDG-PET and 131I-cG250 RIS detected 33 previously unknown metastases, of which 32 were [18F]FDG positive and seven were 131I-cG250 positive. Of the 112 tumour lesions that were documented, [18F]FDG-PET detected 69% (77 out of 112), whereas 131I-cG250 RIS detected only 30% (34 out of 112). In conclusion, [18F]FDG-PET is superior to 131I-cG250 RIS in detecting metastases in patients with metastatic RCC, and therefore seems a promising tool for (re)staging patients with RCC. The usefulness of RIS with a diagnostic dose of 131I-cG250 seems to be restricted to selecting patients for radioimmunotherapy with 131I-cG250.

Value of positron emission tomography with [F-18]fluorodeoxyglucose in patients with colorectal liver metastases: a prospective study.

PURPOSE: To assess prospectively the value of fluor-18-deoxyglucose (FDG) positron emission tomography (PET), in addition to conventional diagnostic methods (CDM), as a staging modality in candidates for resection of colorectal liver metastases. PATIENTS AND METHODS: In 51 patients analyzed for resection of colorectal liver metastases, clinical management decisions were recorded after a complete work-up with CDM. Afterward, FDG-PET scans were performed and any change of clinical management according to FDG-PET results was carefully documented. Discordances between FDG-PET and CDM results were identified and related to the final diagnosis by histopathology, intraoperative findings, and follow-up. RESULTS: In 10 (20%) out of 51 patients, clinical management decisions based on CDM were changed after FDG-PET findings were known. FDG-PET detected unresectable pulmonary (n = 5) and hepatic metastases (n = 1) and ruled out extrahepatic (n = 2) and hepatic disease (n = 2). Due to FDG-PET, eight patients were spared unwarranted liver resection or laparotomy and two other patients were identified as candidates for liver resection. When the results of FDG-PET were regarded as decisive in a retrospective analysis, potential change of management was 29% (15 patients). FDG-PET and CDM showed discordant extrahepatic results in 11 patients (22%) and discordant hepatic results in eight patients (16%). Compared with CDM, FDG-PET resulted in true upstaging (n = 11), true downstaging (n = 5), false upstaging (n = 1), and false downstaging (n = 2). The detection rate of liver metastases on a lesion basis was generally better for computed tomography than for FDG-PET (80% v 65%); this was related to tumor size. CONCLUSION: FDG-PET as a complementary staging method improves the therapeutic management of patients with colorectal liver metastases, especially by detecting unsuspected extrahepatic disease.