Fluorodeoxyglucose positron emission tomography of soft tissue tumours: is a non-invasive determination of biological activity possible?

Since musculoskeletal tumours comprise a large heterogeneous group of entities with different biological behaviour, clinical diagnosis of such lesions can be very difficult. The aim of this prospective study was to assess the usefulness of 2-[F-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the non-invasive evaluation of soft tissue tumours. One hundred and two patients with suspected soft tissue neoplasms were investigated by FDG-PET. The uptake of FDG was evaluated semiquantitatively by determining the tumour to background ratio (TBR). All patients underwent biopsy, resulting in the histological detection of 39 high-grade sarcomas, 16 intermediate-grade sarcomas, 11 low-grade sarcomas, 25 benign tumours, 10 tumour-like lesions such as spontaneous myositis ossificans (n = 6) and one non-Hodgkin lymphoma. All lesions except for two lipomas disclosed an increased FDG uptake. Sarcomas showed significantly higher TBR values than latent or active benign lesions (P<0.001) and aggressive benign lesions (P<0.05). Using a TBR cut-off level of 3.0 for malignancy, sensitivity of FDG-PET was 97.0%, specificity 65.7% and accuracy 86. 3%. From our data there are three main conclusions: (1) Except for patients with pseudotumoral myositis ossificans, lesions with a TBR >3 were sarcomas (91.7%) or aggressive benign tumours (8.3%). (2) Tumours with a TBR <1.5 were latent or active benign lesions, exclusively. (3) The group with intermediate TBR values (<3 and >1. 5) comprised primarily latent or active benign lesions, but also four aggressive benign tumours and two low-grade sarcomas. Our data suggest that FDG-PET represents a useful tool for the evaluation of the biological activity of soft tissue neoplasms.     

Serial Evaluation of Increased Chest Wall F-18 Fluorodeoxyglucose (FDG) Uptake Following Radiation Therapy in Patients With Bronchogenic Carcinoma

PURPOSE: Following radiation therapy for bronchogenic carcinoma, increased FDG accumulation within the irradiated tissue can be identified. This finding has not been well characterized. Therefore, we retrospectively evaluated the time course, frequency, and intensity of increased FDG uptake over a one-year period in patients who had been treated with radiation therapy. MATERIALS AND METHODS: Serial FDG-PET studies (n = 38) were performed in patients (n = 12) with bronchogenic carcinoma before and after radiation therapy. Regions of interest (ROIs) were placed in the chest wall and activity concentrations of posttherapy studies were compared to pretherapy studies. FDG uptake was also described qualitatively relative to mediastinal activity (1-4 scale) by two observers blinded from clinical information. RESULTS: Chest wall radiation port ROI uptake was 18% higher in the 2-month (P = 0.08), 40% higher in the 6-month (P = 0.003), and 32% higher in the 12-month (P = 0.04) posttherapy studies than in non-port ROIs. In 6 patients that clinically had radiation-induced chest wall fibrosis or pneumonitis, visual interpretation identified abnormal chest wall or pleural region FDG uptake in 5/6. In 2/6 patients without clinical chest wall fibrosis, abnormal, chest wall FDG uptake was seen. CONCLUSIONS: Radiation therapy occasionally causes modestly increased soft tissue FDG uptake within irradiated soft tissue in patients being treated for bronchogenic carcinoma, which persists for up to one year after therapy.     

18F-FDG PET in the management of endometrial cancer

Purpose Few studies have investigated the clinical impact of whole-body positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) in endometrial cancer. We aimed to assess the value of integrating FDG-PET into the management of endometrial cancer in comparison with conventional imaging alone.Methods All patients with histologically confirmed primary advanced (stage III/IV) or suspicious/documented recurrent endometrial cancer, with poor prognostic features (serum CA-125 >35 U/ml or unfavourable cell types), or surveillance after salvage therapy were eligible. Before FDG-PET scanning, each patient had received magnetic resonance imaging and/or computed tomography (MRI-CT). The receiver operating characteristic curve method with calculation of the area under the curve (AUC) was used to compare the diagnostic efficacy. Clinical impacts were determined on a scan basis.Results Forty-nine eligible patients were accrued and 60 studies were performed (27 primary staging, 33 post-therapy surveillance or restaging on relapse). The clinical impact was positive in 29 (48.3%) of the 60 scans. Mean standardised uptake values (SUVs) of true-positive lesions were 13.2 (range 5.7–37.4) for central pelvic lesions and 11.1 (range 1.5–37.4) for metastases. The sensitivity of FDG-PET alone (P<0.0001) or FDG-PET plus MRI-CT (P<0.0001) was significantly higher than that of MRI-CT alone in overall lesion detection. FDG-PET plus MRI-CT was significantly superior to MRI-CT alone in overall lesion detection (AUC 0.949 vs 0.872; P=0.004), detection of pelvic nodal/soft tissue metastases (P=0.048) and detection of extrapelvic metastases (P=0.010), while FDG-PET alone was only marginally superior by AUC (P=0.063).Conclusion Whole-body FDG-PET coupled with MRI-CT facilitated optimal management of endometrial cancer in well-selected cases.These data were presented in part at the Tenth Biennial Meeting of the International Gynecologic Cancer Society, Edinburgh, Scotland, October 3–7, 2004     

Fluorodeoxyglucose positron emission tomography of soft tissue tumours: is a non-invasive determination of biological activity possible?

Since musculoskeletal tumours comprise a large heterogeneous group of entities with different biological behaviour, clinical diagnosis of such lesions can be very difficult. The aim of this prospective study was to assess the usefulness of 2-[F-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the non-invasive evaluation of soft tissue tumours. One hundred and two patients with suspected soft tissue neoplasms were investigated by FDG-PET. The uptake of FDG was evaluated semiquantitatively by determining the tumour to background ratio (TBR). All patients underwent biopsy, resulting in the histological detection of 39 high-grade sarcomas, 16 intermediate-grade sarcomas, 11 low-grade sarcomas, 25 benign tumours, 10 tumour-like lesions such as spontaneous myositis ossificans (n = 6) and one non-Hodgkin lymphoma. All lesions except for two lipomas disclosed an increased FDG uptake. Sarcomas showed significantly higher TBR values than latent or active benign lesions (P<0.001) and aggressive benign lesions (P<0.05). Using a TBR cut-off level of 3.0 for malignancy, sensitivity of FDG-PET was 97.0%, specificity 65.7% and accuracy 86.3%. From our data there are three main conclusions: (1) Except for patients with pseudotumoral myositis ossificans, lesions with a TBR >3 were sarcomas (91.7%) or aggressive benign tumours (8.3%). (2) Tumours with a TBR <1.5 were latent or active benign lesions, exclusively. (3) The group with intermediate TBR values (<3 and >1.5) comprised primarily latent or active benign lesions, but also four aggressive benign tumours and two low-grade sarcomas. Our data suggest that FDG-PET represents a useful tool for the evaluation of the biological activity of soft tissue neoplasms. Received 27 November 1998 and in revised form 20 January 1999     

Significance of incidental fluorodeoxyglucose uptake in the parotid glands and its impact on patient management

BACKGROUND AND OBJECTIVES: Minimal-to-low grade fluorodeoxyglucose (FDG) uptake in the parotid glands is regarded as a normal variant in a whole-body survey with FDG-PET. Not frequently, however, a relatively intense or asymmetric FDG uptake is encountered in the parotid glands. The aim of this study was to determine the causes and characteristics of this 'FDG accumulation of uncertain significance' in the parotid glands in patients without any known or suspected pathologies at the time of whole-body FDG-PET. In addition, we also examined patients in whom there was no documented evidence of parotid pathology before FDG-PET scan and a suspicion of disease involvement was first raised in the reports in view of focal uptake in the FDG-PET images. MATERIALS AND METHODS: A total of 25 patients with 49 PET examinations [46 PET and three PET/computed tomography (CT) scans] were identified from the retrospective examination of PET reports and were analyzed in this study. Only those cases with no earlier history of disease involvement of parotid gland or known parotid pathology before FDG-PET were selected for this analysis. These patients were selected from a population of patients with a known malignancy elsewhere who underwent conventional whole-body FDG-PET or PET/CT for staging, disease viability assessment, or treatment monitoring purposes and had demonstrated varying patterns of FDG uptake (unilateral, bilateral, symmetric, or asymmetric) in the parotid glands. FDG uptake in the parotid glands was reported to be of uncertain significance in the majority of these patients and further correlation was suggested in the PET reports. In five patients with asymmetric and focally enhanced FDG uptake, a suspicion of disease involvement was raised in the reports. The results of appropriate correlative investigations with MRI, low-dose nonenhanced attenuation CT images (based on PET/CT scans), and histopathology (in cases in which focal lesions were revealed by the anatomic imaging modalities and biopsy was performed) carried out subsequent to the FDG-PET scans were reviewed for a definitive conclusion with regard to the significance of the FDG uptake in the parotid glands in these patients. In the absence of any focal pathology, clinical and follow-up FDG-PET data were reviewed for a logical conclusion, which were available in a majority of these patients. Standardized uptake values (maximum) were calculated by generating a manual region of interest over FDG activity. The pattern and the intensity of the FDG uptake were correlated with the final diagnosis. RESULTS: In six of the 25 patients with diffuse and symmetrical FDG uptake no clearcut pathology was demonstrated by clinical or radiological examinations. Five patients of this subgroup also demonstrated associated enhanced FDG activity in the submandibular salivary glands. Nineteen patients (76%) demonstrated asymmetric FDG uptake. Among these, focally enhanced uptake was observed in seven patients (28% of the total number of patients and 36.8% of the patients who demonstrated asymmetric FDG uptake in the parotids). Twelve patients (48% of total patients and 63.2% of the patients who demonstrated asymmetric FDG uptake) demonstrated asymmetric and diffuse FDG uptake pattern. No revelation of disease either by the MRI or follow-up clinical and FDG-PET examinations was observed in patients with asymmetric diffuse uptake. Five of the seven patients, who had asymmetric focal uptake in one of the parotids, were found to have focal lesions in either correlative MRI or low-dose nonenhanced CT. The final diagnosis based upon histopathology revealed primary parotid tumors (e.g., Warthin's tumor and pleomorphic adenoma, which presented as FDG-avid parotid incidentaloma) or metastatic disease involvement. CONCLUSION: Both the pattern and intensity of FDG uptake have important implications for differential diagnosis in the salivary glands in whole-body FDG-PET. A bilaterally symmetrical increased uptake is usually physiological. An asymmetrical uptake, especially when focal, would warrant further radiological and histopathological correlation to rule out disease involvement. At times, this can lead to the detection of an asymptomatic hitherto unknown etiology, which would have been otherwise interpreted as a metastatic disease in the background of an existing malignancy in these patients; this is noteworthy as it may have a bearing on the subsequent management of these patients.     

FDG accumulation in aortic walls

A 65-year-old woman with no symptoms underwent whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for cancer screening. FDG accumulation was detected incidentally in her arterial walls, including the aortic wall. She had no history of inflammatory or cardiovascular disease. Although accumulation of FDG is well recognized in the aortic wall when vasculitis is present, this patient showed no symptoms of active vasculitis during the 22-month follow-up period after the PET study. The aortic wall might be a site where FDG accumulates physiologically in elderly persons.     

PET imaging in breast cancer.

The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18F has the advantages of a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. However FDG-PET revealed to be effective in the study of patients with ambiguous mammographies. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complements other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. Several clinical evidences demonstrated that FDG-PET is also able to predict wether cancer will respond to the therapy, or, when applied at the end of the treatment, it can assess the response to the therapy. These statements are coming from the examination of more than 2000 breast cancer patients included in 88 articles or abstracts on studies in which FDG-PET was used for breast cancer detection.     

FDG-PET for the diagnosis of fever of unknown origin: a Japanese multi-center study

Objective

To evaluate the clinical value of 2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) for the diagnosis of fever of unknown origin (FUO), we performed a Japanese multi-center retrospective survey.

Methods

A total of 81 consecutive patients with FUO who underwent FDG-PET at 6 institutions between July 2006 and December 2007 were retrospectively evaluated. FDG uptake was visually evaluated using a 4-grade scale. The efficacy of FDG-PET for the evaluation of FUO, the provision of additional diagnostic information, the clinical impact on therapeutic decisions (4-grade scale), and the diagnostic performance compared with the final diagnosis were evaluated.

Results

The diagnostic results were analyzed according to 4 groups of final diagnoses: infection, arthritis/vasculitis/autoimmune/collagen disease (A/V), tumor/granuloma (T/G), and other/unknown (O/U). Sensitivity was highest in T/G, followed by infection, A/V and O/U [100%(7/7), 89%(24/27), 65%(11/17), 0%(0/1) respectively]. Clinical impact and mean FDG score showed the same tendency. Additional information was highest in infection followed by T/G, A/V, and O/U [76%(22/29), 75%(6/8), 43%(9/21), 23%(5/22), respectively]. The O/U group showed a high specificity (84%, 16/19) and accurately excluded active focal inflammatory diseases and malignancy. The use of steroids for the treatment of fever seemed to mask the lesions and modified the results, especially in the A/V group (4 false negatives in 8 steroid users out of 21 A/V patients). The prevalence of each disease in each hospital significantly affected the effectiveness of FDG-PET for the diagnosis of FUO. The mean FDG uptake score and additional information (70%, 31/44 vs. 30%, 11/37, respectively) in national hospital (NH) was significantly higher than in university hospitals (UH). A Grade 3 clinical impact, in which the FDG PET results changed the clinical decision, was seen in 50% (22/44) of the patients in the NH group and 13.5% (5/37) of the patients in the UH group. The sensitivity (91%, 30/33; 63%, 12/19) and specificity (60%, 6/10; 86%, 12/14) of the results in the NH and UH groups differed. The total sensitivity was 81% (42/52), specificity was 75% (18/24). The NH group included a large number of cases with infectious diseases (50%, 23/44), while the UH group included a large number of A/V cases (38%, 14/37) and O/U cases (41%, 15/37).

Conclusion

FDG-PET for the diagnosis of FUO provided additional diagnostic information and had a high clinical impact, especially among patients with infectious diseases. It was also helpful in cases with unknown or other miscellaneous diseases by allowing the exclusion of focally active diseases. The prevalence of diseases in hospitals significantly affected the effectiveness of FDG-PET for the diagnosis of FUO. FDG-PET is a useful examination providing various degrees of clinical impact for the management of FUO, depending on the characteristics of the patient and the hospital.     

Fluorine-18 fluorodeoxyglucose PET in infectious bone diseases: results of histologically confirmed cases

The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in acute and chronic osteomyelitis and inflammatory spondylitis. The study population comprised 21 patients suspected of having acute or chronic osteomyelitis or inflammatory spondylitis. Fifteen of these patients subsequently underwent surgery. FDG-PET results were correlated with histopathological findings. The remaining six patients, who underwent conservative therapy, were excluded from any further evaluation due to the lack of histopathological data. The histopathological findings revealed osteomyelitis or inflammatory spondylitis in all 15 patients: seven patients had acute osteomyelitis and eight patients had chronic osteomyelitis or inflammatory spondylitis. FDG-PET yielded 15 true-positive results. The tracer uptake correlated with the histopathological findings in each case. Bone scintigraphy performed in 11 patients yielded ten true-positive results and one false-negative result. Follow-up carried out on two patients revealed normal or clearly reduced tracer uptake, which correlated with a normalisation of clinical data. In early postoperative follow-up it was impossible to differentiate between postsurgical reactive changes and further infection using FDG-PET. It is concluded that acute and chronic osteomyelitis of the peripheral as well as the central skeleton can be detected using FDG-PET. Osteomyelitis can be differentiated from soft tissue infection surrounding the bone. Unlike computed tomography and magnetic resonance imaging, FDG-PET is not affected by metal implants used for fixing fractures. FDG-PET demonstrated promising initial results with respect to treatment monitoring. Nevertheless, in the early postoperative phase FDG-PET seems to be of limited value owing to unspecific tracer uptake.     

Arterial inflammation in bronchial asthma

Background

Bronchial asthma is a chronic inflammatory condition associated with increased cardiovascular (CV) events. Here, we assess arterial inflammation, using 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging (FDG-PET/CT), in patients with bronchial asthma and low to intermediate Framingham risk scores (FRS).

Methods

A total of 102 patients underwent FDG-PET/CT imaging for clinical indications. Thirty-four patients (mean age 54.9 ± 16.1) with mild asthma and no known atherosclerotic disease were compared to 2 non-asthmatic groups. The first control group (n = 34) were matched by age, gender, and FRS. The second control group (n = 34) had clinical atherosclerosis and were matched by gender. Thereafter, arterial FDG uptake on PET images was determined, while blinded to patient identifiers.

Results

Target-to-background-ratio (TBR) in the aorta was higher in asthmatics vs non-asthmatic FRS-matched controls (1.96 ± 0.26 vs 1.76 ± 0.20; P < .001). The aortic TBR remained elevated in asthmatics vs non-asthmatic controls after adjusting traditional CV risk factors (P < .001). An inverse correlation was observed between FDG uptake and lung function, FEV₁ (P = .02) and peak flow (P = .03).

Conclusions

Bronchial asthma is associated with increased arterial inflammation beyond that estimated by current risk stratification tools. Further studies are required to evaluate whether attenuation of systemic inflammation will decrease CV events.     

The value of FDG-PET in patients with painful total knee arthroplasty

Purpose The purpose of this study was to evaluate ¹⁸F-fluorodeoxyglucose (FDG) uptake in patients with painful total knee arthroplasty and to relate FDG uptake to the location of soft tissue pain.Methods Twenty-eight patients with painful total knee arthroplasty had a clinical examination, standard radiographs, CT measurement of rotation of the femoral component and FDG-PET (18 PET/CT, 10 PET). The diagnosis of infection was based on microbiological examinations of surgical specimens (n=12) or clinical follow-up for at least 6 months (n=16), ^99mTc-labelled monoclonal antibody scintigraphy and joint aspiration.Results Twenty-seven of 28 patients presented with diffuse synovial FDG uptake. Additional focal extrasynovial FDG uptake was observed in 19 knees. Twenty-four of the 28 patients had a diagnosis of internal femoral malrotation. The remaining four patients showed no rotation (0°) and 3°, 4° and 7° of external rotation, respectively. Three patients presented with the additional diagnosis of an infected total knee replacement. Pain was described as diffuse (n=10) or focal (n=18). In two knees a relationship between pain location and FDG uptake was observed. Of ten patients with a severe internal femoral component rotation (>6°), seven had focal uptake, four in the femoral periosteum and three in the tibial periosteum. The difference between knees with severe malrotation and the remaining knees was not significant (p=1.000, Fisher's Exact Test).Conclusion Diffuse synovial and focal extrasynovial FDG-PET uptake is commonly found in patients with malrotation of the femoral component and is not related to pain location. The information provided by FDG-PET does not contribute to the diagnosis and management of individual patients with persistent pain after total knee replacement.     

Spontaneous regression of follicular, mantle cell, and diffuse large B-cell non-Hodgkin's lymphomas detected by FDG-PET imaging

Spontaneous regression of non-Hodgkin lymphoma (NHL) has been reported in low-grade tumors but is an extremely rare event in intermediate- and high-grade disease. Documentation of spontaneous regression by serial fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging has not been reported in the literature. We present 3 cases of spontaneous regression, 1 each of follicular lymphoma (FL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL), which showed spontaneous regression on serial FDG-PET imaging. All patients underwent serial whole-body FDG-PET scans 60 minutes after intravenous injection of 9-11 mCi of this radiotracer. None of them had any chemotherapy, radiotherapy, or surgery after the baseline PET scan. Spontaneous regression of disease in all 3 cases was correlated with conventional imaging and clinical course. All 3 patients had positive FDG-PET results on their baseline scan. There was complete disappearance of FDG uptake on a follow-up PET scan for the patient with follicular lymphoma. These results suggest complete regression. The patients with MCL and DLBCL both showed a significant reduction in FDG uptake on serial whole-body PET scans, suggesting partial regression in both cases. Although spontaneous regression of lymphoma is uncommon, this phenomenon can be successfully demonstrated by FDG-PET imaging. Therefore, serial PET imaging may play an important role in detecting this unusual event and may further enhance our understanding of the biologic behavior of this malignancy.     

Persistent non-specific FDG uptake on PET imaging following hip arthroplasty

Hip arthroplasty is a common surgical procedure, but the diagnosis of infection associated with hip arthroplasty remains challenging. Fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been shown to be a promising imaging modality in settings where infection is suspected. However, inflammatory reaction to surgery can result in increased FDG uptake at various anatomic locations, which may erroneously be interpreted as sites of infection. The purpose of this study was to assess the patterns and time course of FDG accumulation following total hip replacement over an extended period of time. Firstly, in a prospective study nine patients with total hip replacement were investigated to determine the patterns of FDG uptake over time. Three FDG-PET scans were performed in each patient at about 3, 6 and 12 months post arthroplasty. Secondly, in a retrospective analysis, the medical and surgical history and FDG-PET imaging results of 710 patients who had undergone whole-body scans for the evaluation of possible malignant disorders were reviewed. The history of arthroplasty and FDG-PET findings in the hip region were reviewed for this study. Patients with symptomatic arthroplasties or related complaints during FDG-PET scanning were excluded from the analysis. During the entire study period, all nine patients enrolled in the prospective study were demonstrated to have increased FDG uptake around the femoral head or neck portion of the prosthesis that extended to the soft tissues surrounding the femur. Among the patients reviewed in the retrospective study, 18 patients with a history of 21 hip arthroplasties who were asymptomatic at the time of FDG-PET scan met the criteria for inclusion. The time interval between the hip arthroplasty and the FDG-PET study ranged from 3 months to 288 months (mean+/-SD: 80.4+/-86.2 months). In 81% (17 of 21) of these prostheses, increased FDG uptake could be noted around the femoral head or neck portion of the prosthesis. The average time interval between arthroplasty and FDG-PET scan in these patients was 71.3 months. In only four prostheses (19%, 4 of 21) was no abnormally increased FDG uptake seen around the prostheses or adjacent sites. The average time interval in these patients was 114.8 months. It is concluded that following hip arthroplasty, non-specifically increased FDG uptake around the head or neck of the prosthesis persists for many years, even in patients without any complications. Therefore, to minimize the number of false-positive results for infection with PET studies obtained to evaluate a painful hip prosthesis, caution should be exercised when interpreting FDG uptake around the head or neck portion of the prosthesis.     

Fluorine-18 fluorodeoxyglucose positron emission tomography in infectious bone diseases: results of histologically confirmed cases

The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in acute and chronic osteomyelitis and inflammatory spondylitis. The study population comprised 21 patients suspected of having acute or chronic osteomyelitis or inflammatory spondylitis. Fifteen of these patients subsequently underwent surgery. FDG-PET results were correlated with histopathological findings. The remaining six patients, who underwent conservative therapy, were excluded from any further evaluation due to the lack of histopathological data. The histopathological findings revealed osteomyelitis or inflammatory spondylitis in all 15 patients: seven patients had acute osteomyelitis and eight patients had chronic osteomyelitis or inflammatory spondylitis. FDG-PET yielded 15 true-positive results. The tracer uptake correlated with the histopathological findings in each case. Bone scintigraphy performed in 11 patients yielded ten true-positive results and one false-negative result. Follow-up carried out on two patients revealed normal or clearly reduced tracer uptake, which correlated with a normalisation of clinical data. In early postoperative follow-up it was impossible to differentiate between postsurgical reactive changes and further infection using FDG-PET. It is concluded that acute and chronic osteomyelitis of the peripheral as well as the central skeleton can be detected using FDG-PET. Osteomyelitis can be differentiated from soft tissue infection surrounding the bone. Unlike computed tomography and magnetic resonance imaging, FDG-PET is not affected by metal implants used for fixing fractures. FDG-PET demonstrated promising initial results with respect to treatment monitoring. Nevertheless, in the early postoperative phase FDG-PET seems to be of limited value owing to unspecific tracer uptake. Received 4 November 1999 and in revised form 20 January 2000     

Early diagnosis of recurrent breast cancer with FDG-PET in patients with progressive elevation of serum tumor markers.

BACKGROUND: The aim of this work is to assess the diagnostic value of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG), in the early detection of tumour recurrence in already treated breast cancer patients in apparent complete remission and with a progressive elevation of tumour markers CEA and/or CA 15.3 without any other clinical or instrumental signs of relapses. METHODS: The author studied 45 women (mean age 58+/-12, range 35-80 years) with histological diagnosis of breast cancer who underwent a tumour marker-guided whole body FDG-PET. All patients were in remission, without any other clinical or instrumental signs of relapses, except for the progressive elevation of CA 15.3 and/or CEA, tested during the follow-up. FDG-PET results were controlled by pathology when histological sampling was possible, by other conventional imaging modalities (US, X-rays, CT, MRI) and/or by clinical follow-up up to 12 months at least. RESULTS: FDG-PET findings were evaluated in 38 patients: 27 resulted positive. Among these 27 PET positive patients 24 were true positive and 3 false positive. Tumour marker guided FDG-PET was also able to discover 3 unknown neoplasms not visualized by other modalities. PET revealed 54 sites of intense focal FDG uptake. The anatomical distribution of these sites was 19 skeleton, 18 lymph node basins, 5 liver, 5 pelvic region, 1 lung, 1 pericardium, 1 pleura, 1 contralateral breast, 2 peritoneum and 1 thyroid bed. Forty-eight of these 54 sites of FDG accumulation were confirmed to be metastases. FDG-PET resulted negative in 11 patients and only in 2 of them the other diagnostic modalities were able to discover metastatic lesions; we had 9 true negative and 2 false positive RESULTS. On the basis of our investigation the performances of tumour marker guided FDG-PET per patient are as follows: sensitivity 92% (24/26), specificity 75% (9/12), positive predictive value 89% (24/27), negative predictive value 82% (9/11), accuracy 87% (33/38). CONCLUSIONS: This study demonstrated the clinical utility of tumour marker-guided PET in the follow-up of breast cancer patients. This diagnostic approach allowed to modify the clinical management in those patients in whom a tumor relapse or unexpected primary neoplasm was discovered.     

Metastatic myxoid liposarcomas: imaging and histopathologic findings

Objective The objective was to describe the imaging and histopathologic characteristics of metastatic myxoid liposarcomas. Materials and methods This retrospective study was approved by the institutional review board and complied with HIPAA guidelines. The study group comprised 12 patients with metastatic myxoid liposarcoma who underwent MRI, CT, or FDG-PET. The location and imaging characteristics of the metastatic lesions were recorded, and the histopathology of all metastatic lesions was reviewed. Results There were 23 histologically proven metastases in 12 patients. Based on imaging criteria, there were 41 metastases. The mean time from the diagnosis of primary tumor to the first metastasis was 4.4 years. Sixty-seven percent of patients had bone and soft tissue metastases, 33% had pulmonary metastases, 33% had liver metastases, 25% had intra-abdominal, and 16% retroperitoneal metastases. CT demonstrated well-defined lobulated masses with soft tissue attenuation in all cases, without macroscopic fat component. In cases of osseous metastases, CT showed mixed lytic and sclerotic foci, with bone destruction in advanced cases. MRI demonstrated fluid-like signal intensity with mild heterogeneous enhancement in cases of soft tissue metastases. In osseous metastases, MRI showed avid heterogeneous enhancement. FDG-PET showed no significant FDG uptake for all metastases. MRI was the most useful imaging modality for osseous and soft tissue metastases. Conclusion Myxoid liposarcomas are soft tissue sarcomas, with a high prevalence of extrapulmonary metastases. The bones and soft tissues were the most common site of involvement, followed by the lungs and liver. MRI was the most sensitive modality in the detection of osseous and soft tissue metastases, and is the recommended modality for the diagnosis and follow-up of bone and soft tissue involvement.     

Correlative Whole-Body FDG-PET and Intraoperative Gamma Detection of FDG Distribution in Colorectal Cancer

Purpose: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is the superior imaging modality for detection of primary and recurrent colorectal cancer compared to magnetic resonance imaging (MRI) or computerized tomography (CT). We investigated the feasibility of developing intraoperative procedures for detection of FDG in tumor deposits in order to assist the surgeon in achieving an optimal reduction of tumor burden.Procedures: Fourteen patients (45-83 years of age) were scanned using FDG-PET followed by Gamma Detection Probe evaluation at laparotomy. One patient did not have a pre-operative FDG-PET scan. The collimated detector probe contained a CdZnTe crystal (7mm diameter x 2mm thick). We used a lower window setting of 200 KeV and an open upper window setting. Fasted patients were given an IV bolus of FDG (4.0-5.7 mCi) 15-20 minutes prior to preparation for surgery. Catheterization and the diuretic Lasix were used to remove FDG activity from the bladder. The time from FDG injection to intraoperative GDP data acquisition varied from 58-110 minutes.Results: In all patients, the GDP detected background activity in normal tissues (aorta, colon, liver, kidney, abdominal wall, mesentery, and urinary bladder). The GDP correctly identified single or multiple tumor foci in 13/14 patients as noted by an audible signal from the control unit (3 S.D. above counts obtained from normal tissues). These tumor foci corresponded to regions of high FDG uptake as seen on FDG-PET scans. The one case that the GDP did not localize was a recurrent mucin pseudomyxoma-producing tumor (acellular, mucinous deposits). Ex vivo GDP evaluations demonstrated significant tumor:normal adjacent tissue activity (audible signals in 6/6 tumor samples tested).Conclusions: These data demonstrate that tumors identified from pre-operative whole-body PET scans can be localized during surgery utilizing a gamma probe detector and FDG.     

Value of F-18 FDG hybrid camera PET and MRI in early takayasu aortitis

Takayasu aortitis (TA) is a chronic inflammatory and fibrotic vasculitis of large- and medium-sized arteries. Early stages of the disease show a panarteritis and inflammatory wall thickening of the aorta and its branches, whereas advanced (fibrotic) stages comprise stenosis, aneurismatic transformation and occlusion. Magnetic resonance imaging visualises early-stage disease with high accuracy and is considered to be the method of choice in the diagnosis of TA. The aim of this article is the detailed comparison of FDG-PET performed with a hybrid camera and MR imaging in five patients with early TA. Five patients (median age 60 years) were enrolled during an ongoing prospective study on [18F]2'-deoxy-2-fluoro-D-glucose (FDG) hybrid camera PET in patients with fever of unknown origin (FUO). These patients underwent MR imaging after establishing the diagnosis of TA. Abnormal FDG uptake in the wall of the aorta was noted in all patients. The bracheocephalic artery and the common carotid arteries were visualized in 3 cases. Increased uptake of the subclavian artery was found in 3 patients and in 4 patients pathological uptake was noted in the ilio-femoral vessels. Of 34 vascular regions studied, 26 (76%) showed elevated FDG uptake. On transversal MR images vessel wall thickening and contrast enhancement of the thoracic aorta was found in 4 patients (ascending aorta/aortic arch: n=2; descending aorta: n=3; abdominal aorta: n=1). Additionally, vessel wall pathologies of the subclavian and the common carotid arteries could be shown in 1 patient and in another patient in the ilio-femoral arteries. No abnormalities were found using contrast-enhanced MR angiography. Of 28 vascular regions studied, 9 (32%) showed vasculitis on MRI. The FDG-PET is a suitable whole-body screening method in the primary diagnosis of early TA, especially in those cases with early disease that present with uncharacteristic symptoms such as FUO. Both MRI and MRA remain indispensable in the exact determination of the pathomorphological changes and in the documentation of complications such as stenosis, aneurismatic transformation and occlusion. Electronic Publication     

Evaluation of hemangioma by positron emission tomography: role in a multimodality approach

PURPOSE: The relative utility of various preoperative diagnostic imaging modalities for the evaluation of hemangioma of the extremities, including positron emission tomography (PET) (using 18F-fluoro-2-deoxy-D-glucose [FDG] and fluorine-18 alpha-methyltyrosine [FMT]), computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA), was investigated. METHODS: Imaging findings in 16 patients with 16 histopathologically documented hemangiomas of the extremities were retrospectively reviewed. Preoperative imaging included: FDG-PET (n = 16), FMT-PET (n = 12), MRI (n =16), CT (n =11), and DSA (n =14). RESULTS: All 16 lesions examined by PET with FDG and/or FMT showed accumulation. The standardized uptake values (SUVs) for FDG-PET for the 16 examined tumors ranged from 0.7 to 1.67; for FMT-PET, they ranged from 0.14 to 1.00. The SUVs with both tracers indicated the benign nature of the tumor. Computed tomography demonstrated variable attenuation and phleboliths in two patients. The MRI signal characteristics were relatively consistent: heterogeneous signals were slightly higher than those of skeletal muscle on T1-weighted images and brighter than those of subcutaneous fat on T2-weighted images. The pooling and cotton-wool staining depicted in DSA was found to be significantly correlated with FDG accumulation, suggesting that localized blood retention-induced ischemia may accelerate anaerobic glycolysis, which leads to high FDG uptake. CONCLUSION: Although plain radiography, CT, MRI, and angiography may provide anatomic extent and be pathognomonic, FDG-PET and FMT-PET may be the most reliable among the studied imaging modalities for differentiating benign hemangiomas from other soft tissue tumors, especially malignant neoplasms.     

Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography

BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) has been shown to accumulate in inflamed tissues. However, it is not known whether vascular inflammation can be measured noninvasively. The aim of this study was to test the hypothesis that vascular inflammation can be measured noninvasively by use of positron emission tomography (PET) with FDG. METHODS AND RESULTS: Inflamed atherosclerotic lesions were induced in 9 male New Zealand white rabbits via balloon injury of the aortoiliac arterial segment and exposure to a high cholesterol diet. Ten rabbits fed standard chow served as controls. Three to six months after balloon injury, the rabbits were injected with FDG (1 mCi/kg), after which aortic uptake of FDG was assessed (3 hours after injection). Biodistribution of FDG activity within aortic segments was obtained by use of standard well gamma counting. FDG uptake was also determined noninvasively in a subset of 6 live atherosclerotic rabbits and 5 normal rabbits, via PET imaging and measurement of standardized uptake values over the abdominal aorta. Plaque macrophage density and smooth muscle cell density were determined by planimetric analysis of RAM-11 and smooth muscle actin staining, respectively. Biodistribution of FDG within nontarget organs was similar between atherosclerotic and control rabbits. However, well counter measurements of FDG uptake were significantly higher within atherosclerotic aortas compared with control aortas (P < .001). Within the upper abdominal aorta of the atherosclerotic group (area of greatest plaque formation), there was an approximately 19-fold increase in FDG uptake compared with controls (108.9 +/- 55.6 percent injected dose [%ID]/g x 10(3) vs 5.7 +/- 1.2 %ID/g x 10(3) [mean +/- SEM], P < .001). In parallel with these findings, FDG uptake, as determined by PET, was higher in atherosclerotic aortas (standardized uptake value for atherosclerotic aortas vs control aortas, 0.68 +/- 0.06 vs 0.13 +/- 0.01; P < .001). Moreover, macrophage density, assessed histologically, correlated with noninvasive (PET) measurements of FDG uptake (r = 0.93, P < .0001). In contrast to this finding, FDG uptake did not correlate with either aortic wall thickness or smooth muscle cell staining of the specimens. CONCLUSION: These data show that FDG accumulates in macrophage-rich atherosclerotic plaques and demonstrate that vascular macrophage activity can be quantified noninvasively with FDG-PET. As such, measurement of vascular FDG uptake with PET holds promise for the noninvasive characterization of vascular inflammation.