Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG).

Inflammation contributes to atherosclerotic plaque remodeling, enlargement and rupture. Non-invasive imaging of coronary artery inflammation could help target therapy to 'vulnerable' atheromata, but is limited because of small tissue mass and arterial motion. Local radiopharmaceutical imaging may overcome some of these limitations. We used a positron-sensitive fiberoptic probe, which can distinguish positron emissions from annihilation photons, to identify diseased from healthy endothelium in an atherosclerotic model. New Zealand White rabbits underwent Fogarty-catheter injury of an iliac artery and then were fed a high-fat diet for 3 weeks. Fasted animals received 90-180 MBq of 18-fluorodeoxyglucose (FDG) 2-4 h before sacrifice and harvest of injured and uninjured iliacs. Arteries were incised longitudinally and the probe was placed in contact with the arterial intima. Multiple measurements were obtained along 1 cm artery segments in 60 s intervals, and corrected for 18F decay and background. Measurements were recorded over 93 injured and normal artery segments in 11 animals. Mean probe Z-scores were 4.8-fold higher (CI 3.4-6.3) over injury atherosclerosis compared with uninjured normal iliac artery segments (P<0.001). Gamma counting confirmed that injured artery segments accumulated more FDG per gram than did normal segments (0.203% x kg injected dose per gram of tissue versus 0.042, P<0.001). Non-arterial tissue also accumulated FDG avidly, particularly reticuloendothelial tissues and blood. Delayed sacrifice, 4 h compared with 2 h after animal FDG injection, further reduced blood background counts and improved the signal-to-noise ratio. Histopathology confirmed that injured iliac artery had significantly higher intimal and medial cross-sectional area compared with uninjured artery. Injured artery also had significantly higher macrophage and smooth muscle cell density. Positron-sensitive probe counts correlated with the intima to media ratio (r =0.63, P = 0.03). Our positron-sensitive probe distinguishes atherosclerotic from healthy artery in a blood-free field. Intravascular study of plaque biology may be feasible using FDG and a positron-sensitive probe.

Metabolic response of non-Hodgkin's lymphoma to 131I-anti-B1 radioimmunotherapy: evaluation with FDG PET.

UNLABELLED: 131I-anti-B1 (CD20) radioimmunotherapy (RIT) is a promising approach for treatment of non-Hodgkin's lymphoma (NHL). We assessed the tumor metabolic response to RIT using FDG PET. METHODS: We examined 14 patients with NHL, who were given first a tracer dose of 131I-anti-B1 and then RIT, each preceded by infusion of unlabeled anti-B1. In 8 of 14 patients, PET was performed at baseline and 33-70 d after RIT. The other 6 patients underwent PET at baseline, 6-7 d after the tracer dose, and 5-7 d after RIT to estimate the early response to tracer dose and RIT. To assess tumor FDG uptake, standardized uptake value normalized for lean body mass (SUV-lean) was measured 1 h after FDG injection. RESULTS: After RIT, complete response was observed in 6 patients, partial response in 6, and no response in 2. At 33-70 d after RIT, mean SUV-lean of 6 responders markedly declined to 41% of the baseline value (P < 0.002). Soon after tracer dose and after RIT, mean SUV-lean of the other 6 responders decreased to 79% and 62% of the baseline values, respectively (P < 0.05). In 2 nonresponders, SUV-lean did not significantly decline from the baseline value at 37 d after RIT. CONCLUSION: FDG PET metabolic data obtained 1-2 mo after RIT correlate well with the ultimate best response of NHL to RIT, more significantly than the early data after tracer dose or RIT. FDG uptake in NHL may decline gradually after RIT in responding patients.

Splenic fluorodeoxyglucose uptake increased by granulocyte colony-stimulating factor therapy: PET imaging results.

UNLABELLED: Using PET, we investigated the change in 18F-fluorordeoxyglucose (FDG) uptake in the spleen after granulocyte colony-stimulating factor (G-CSF) treatment. METHODS: Forty-two FDG PET scans in 12 patients with locally advanced breast cancer who received G-CSF treatment were studied (12 baseline, 10 during G-CSF, 20 after G-CSF treatment). The PET images obtained at 50-60 and 60-70 min after intravenous FDG (370 MBq) injection were assessed visually and were compared with those before G-CSF treatment. For a semiquantitative index of FDG uptake, we determined the standardized uptake value calculated on the basis of predicted lean body mass (SUL) on these images, and we calculated the SUL ratios normalized to their baseline SUL values. RESULTS: During G-CSF treatment (n = 10), 9 scans (90%) showed increased splenic FDG uptake (3 slightly, 6 substantially). After G-CSF treatment (n = 20), 13 (65%) showed no change, 7 (35%) showed slightly increased uptake, but no case showed substantially increased FDG uptake in the spleen (P = 0.0003). Out of 30 PET scans obtained during and after G-CSF treatment, 16 (53%) showed increased FDG uptake in the spleen (10 slightly, 6 substantially), whereas 26 (87%) showed increased bone marrow FDG uptake (14 slightly, 12 substantially). The FDG uptake in other normal organs (liver, blood and lung) showed no change during or after G-CSF treatment. Similar to the change in the bone marrow, the SULs in the spleen significantly increased during G-CSF treatment (baseline, 1.50+/-0.31, versus during G-CSF, 2.69+/-0.84; P = 0.0004), then decreased after discontinuation of G-CSF (1.65+/-0.23). There was a significant correlation between the SUL ratios in the spleen and those in the bone marrow (r = 0.778, P < 0.0001), whereas there were no correlations between those in other organs and those in the bone marrow. CONCLUSION: Substantially increased FDG uptake was observed in the spleen during and after G-CSF treatment, although this change was less frequent and not as marked as the change observed in the bone marrow. The recognition and understanding of this phenomenon will be increasingly important when interpreting FDG PET images in cancer patients to avoid confusing this normal phenomenon with pathological splenic (tumor) involvement.

Evaluation of FDG PET in patients with cervical cancer.

UNLABELLED: Although many human cancers can be imaged by 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and PET, there is little clinical experience with FDG PET in cervical cancer. The purpose of this study was to evaluate the feasibility of FDG PET scans on patients with cervical cancer. METHODS: FDG PET scans were performed on 21 patients with histologically proven uterine cervical cancer (17 newly diagnosed, 4 recurrence). After two levels of transmission scanning, approximately 370 MBq FDG were injected, and dynamic scans over 60 min were obtained at the level of suspected tumors, followed by static scans. Postvoid scans were also obtained in 11 patients to minimize FDG activity in the urinary bladder. FDG uptake was interpreted visually and classified into 4 grades (0 = normal, 1 = probably normal, 2 = probably abnormal and 3 = definitely abnormal). For a semiquantitative index of FDG uptake in tumors, the standardized uptake value (SUV) corrected by predicted lean body mass (SUL) was calculated and compared. The detectability of lymph node metastases by PET was compared with that by CT. RESULTS: Of the 21 newly diagnosed or recurrent cancers, 16 (76%) were detected by FDG PET without use of postvoid imaging (i.e., interpreted as grade 2 or 3). The SULs of tumors ranged from 2.74-13.03, with a mean of 8.15 +/- 3.00 (SUV range 3.68-14.94, mean 10.31 +/- 3.19). There was no significant relationship between the SUL of cervical cancer and the clinical stage. Postvoid FDG PET images substantially reduced the tracer activity in the urinary bladder and improved the visualization of cervical cancers, with three additional cases detected using the postvoid images. In the 11 patients with postvoid imaging, all 11 cancers (100%) were detected. FDG PET detected lymph node metastases in 6 (86%) of 7 patients with known metastases, whereas CT was positive in 4 patients (57%), equivocal in 2 patients (29%) and negative in 1 patient (14%). All PET and CT scans were true-negative in the patients with no lymph node metastases (interpreted as grade 0 or 1 by PET, and as negative by CT). CONCLUSION: These preliminary data demonstrate the feasibility of FDG PET imaging in patients with cervical cancer. FDG PET appears to be promising for detecting untreated or recurrent cervical cancers and lymph node metastases, although the excreted FDG in the urine remains problematic in some cases.

Glucose transporters and FDG uptake in untreated primary human non-small cell lung cancer.

UNLABELLED: PET imaging of malignant tumors with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) as a tracer is a noninvasive diagnostic and prognostic tool that measures tumor metabolism. In this study, we assessed the relationships between FDG uptake and the expression of facilitative glucose transporters, the sizes of populations of proliferating cells and infiltrating macrophages in patients with primary non-small cell lung cancers (NSCLC). METHODS: FDG uptake and the expression of five glucose transporters and the proportions of proliferating cell and macrophage populations were studied in paraffin sections from untreated primary lung cancers by immunohistochemistry. The patients were imaged with FDG PET before surgery. RESULTS: All tumors could be detected by FDG PET. Uptake was correlated with tumor size (P = 0.004). FDG uptake was lower in adenocarcinomas (ACs) than in squamous cell carcinomas (SQCs) (P = 0.03) or large cell carcinomas (P = 0.002) [standardized uptake value corrected for lean body mass (SUL) = 5.42 +/- 2.77, 8.04 +/-3.25 and 10.42 +/- 4.54, respectively]. Glut-1 expression was significantly higher than that of any other transporter. All tumors tested (n = 23) were Glut-1-positive (70.8% +/- 26.1% of tumor cell area was positive and staining intensity was 2.8 +/- 1.2). Glut-1 expression was higher in SQCs (78% +/- 17.8% and 3.5 +/-0.6) than in ACs (47.5% +/- 30.3% and 1.6 +/- 1.1; P = 0.044 for positive tumor cell area and P = 0.005 for staining intensity). Proliferating cells constituted 15.3% +/- 13.1% of the cancer cells, and the average number of macrophages was 7.8% +/- 6.3%; neither correlated with FDG uptake. CONCLUSION: In this population of patients with NSCLC, Glut-1 is the major glucose transporter expressed. Both FDG uptake and Glut-1 expression appear to be associated with tumor size. No association was found between FDG uptake and either macrophage or proliferative cell populations.

Capabilities of two- and three-dimensional FDG-PET for detecting small lesions and lymph nodes in the upper torso: a dynamic phantom study.

The capabilities and limitations of two-(2D) and three-dimensional (3D) fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting small tumors and lymph nodes were studied in a phantom modeling the human chest and axilla. Multiple dual-radionuclide phantom studies were performed. Five hollow spheres ranging in diameter from 3 mm to 15 mm were filled with carbon-11 and placed in the axillary and mediastinal regions of an anthropomorphic phantom containing hollow organs filled with 18F to simulate FDG uptake 1 h after injection. Dynamic imaging was performed to acquire PET images with varying target-to-background ratios. Imaging was performed in 2D and 3D acquisition modes, with and without attenuation correction, on a modern PET scanner. Lesion detectability was visually and quantitatively assessed. For objects larger than 9 mm in diameter, target-to-background ratios ranging from approximately 3:1 to approximately 10:1 were detectable. Objects < 9 mm in diameter required a target-to-background ratio of >/=18:1. Target-to-background ratios required for lesion detectability were equivalent for 2D and 3D PET images with and without attenuation correction. In conclusion, 2D and 3D PET with attenuation correction consistently detected "tumors" >/= 9 mm. Lesions < 9 mm could be detected if there was high enough tumor uptake. No statistically significant differences in lesion detection were found for 2D versus 3D PET, or for attenuation-corrected versus non-attenuation-corrected images.

Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results.

The purpose of this study was to evaluate the feasibility of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET) for rapid detection of human infections. Eleven patients who were known or suspected to be harboring various infections were studied with FDG-PET. Dynamic scans over the putative infection sites were performed immediately after FDG (370 MBq) injection through 60 min, and static images including multiple projection images were then obtained. FDG uptake was assessed visually into four grades (0, normal; 1, probably normal; 2, probably abnormal; 3, definitely abnormal). For the semiquantitative index of FDG uptake in infections, the standardized uptake value of FDG normalized to the predicted lean body mass (SUV-lean, SUL) was determined from the images obtained at 50-60 min after FDG injection. PET results were compared with final clinical diagnoses. Eleven lesions in eight patients, which were interpreted as grade 2 or 3 by FDG-PET, were all concordant with active infectious foci. The SUL values of infections ranged from 0.97 to 6.69. In two patients, FDG-PET correctly showed no active infection. In one patient, it was difficult to detect infectious foci by FDG-PET due to substantial normal background uptake of FDG. In total, FDG-PET correctly diagnosed the presence or absence of active infection in 10 of 11 patients. Fusion images of PET with computed tomography showed the most intense FDG uptake to be within an abscess wall. In conclusion, FDG-PET appears to be a promising modality for rapid imaging of active human infections. More extensive clinical evaluation is warranted to determine the accuracy of this method.

Oncologic diagnosis with 2-[fluorine-18]fluoro-2-deoxy-D-glucose imaging: dual-head coincidence gamma camera versus positron emission tomographic scanner.

PURPOSE: To compare the performance of a dual-head single photon emission computed tomographic (SPECT) Anger camera operated in coincidence mode with that of a dedicated positron emission tomographic (PET) scanner in the imaging of cancer with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). MATERIALS AND METHODS: Thirty-one patients with known or suspected malignant neoplasms underwent imaging with both methods, and the images were read blindly. Diagnostic performance on a lesion-by-lesion basis was compared with attenuation-corrected PET as the standard of reference. RESULTS: Of a total of 109 discrete lesions depicted at PET, 60 (relative sensitivity, 55%) were identified on the coincidence-mode images. Of the nodules or masses depicted at PET, 13 (93%) of 14 lung nodules or masses, 20 (65%) of 31 mediastinal lymph nodes, five (71%) of seven lesions in the neck, five (55%) of nine axillary lymph nodes, 11 (50%) of 22 bone metastases, and six (23%) of 26 abdominal tumor deposits were correctly identified on the coincidence gamma camera images. CONCLUSION: These preliminary findings indicate FDG imaging with a modified dual-detector gamma camera operating in coincidence mode can depict many of the lesions depicted with a PET scanner, particularly in the lungs. Sensitivity for lesions detected at dedicated FDG PET was poor in the abdomen and in all locations outside the lungs for tumor deposits generally less than 1.5 cm in short-axis diameter.

Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy.

PURPOSE: To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on bone marrow glucose metabolism in rodents and in patients, as assessed by 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) uptake measured directly or by positron-emission tomography (PET) scanning. MATERIALS AND METHODS: Groups of three rats received either daily saline, G-CSF, or GM-CSF injections for 7 days. After treatment, FDG was injected and F-18 activities in tissues measured 1 hour later. Twenty-two breast cancer patients treated with multiagent chemotherapy were sequentially studied with PET. Eleven patients received G-CSF therapy as an adjunct to chemotherapy, while 11 received chemotherapy only. The standardized uptake value-lean (SUL) of bone marrow FDG uptake was measured and compared. RESULTS: In rats, bone marrow F-18 activity was significantly higher in both CSF groups than in the saline group (G-CSF, 0.44 +/- 0.08; GM-CSF, 0.33 +/- 0.02; saline, 0.18 +/- 0.02% injected dose [ID]/g x kg; P < .05), but the other normal tissues had comparable biodistributions to controls. In breast cancer patients, the FDG uptake of bone marrow did not change with chemotherapy alone; however, marrow uptake was increased after treatment with G-CSF. The dose of G-CSF and duration of treatment were correlated with the extent of increase in FDG uptake. The SUL of bone marrow was as follows: baseline, 1.56 +/- 0.23; after one cycle, 3.13 +/- 1.40 (P < .01); after two cycles, 2.22 +/- 0.85 (P < .05); and after three cycles, 2.14 +/- 0.79 (P < .05), respectively. Although the FDG uptake of bone marrow declined after G-CSF treatment was completed, it was higher than the baseline level for up to 4 weeks postcompletion of G-CSF and the elevated marrow FDG uptake was sustained longer than the period of blood neutrophil count elevation. CONCLUSION: Substantial increases in bone marrow FDG uptake are rapidly induced by CSF treatments and should not be misinterpreted as diffuse bone marrow metastases.

Uptake of 2-deoxy-2-[18F]fluoro-D-glucose in the normal testis: retrospective PET study and animal experiment.

Our retrospective PET and animal studies were conducted on a total of eight patients with normal testes and five male Sprague-Dawley rats. All the rats were necropsied at 60 minute post-injection of FDG, and the organs were removed and counted. The human tests were visualized on 60-70 minute FDG-PET images and whole- or partial-body images in all of the patients. The correlations between patient age over 50 years old and testis-to-muscle ratios, and patient age and SUVs were statistically significant, r = -0.755, p < 10(-6)(n = 7), r = -0.900, p < 0.007 (n = 4), respectively. FDG uptake of the rat tests was 0.162 +/- 0.004% kg injected dose/g (n = 5). The uptake was approximately 6.0 and 3.6 times as high as muscle and blood levels, respectively. In conclusion, there is substantial uptake of FDG into the normal testis which declines with age. The normal levels of FDG uptake in the testis relative to the patient's age should be considered in the interpretation of FDG scans of the inguinal and lower pelvic regions.

Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer.

The purpose of this study was to assess the feasibility of imaging of bladder cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. We studied 12 patients with histologically proven bladder cancer who had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of the urinary bladder with 1000-3710 ml saline was performed during nine of the studies. Dynamic and static PET images were obtained, and standardized uptake value images were reconstructed. FDG-PET scanning was true-positive in eight patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor mass lesions confirmed pathologically or clinically, 16 (80%) were detected by FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions and two of three proven regional lymph node metastases. FDG-PET was also capable of differentiating viable recurrent bladder cancer from radiation-induced alterations in two patients. In conclusion, these preliminary data indicate the feasibility of FDG-PET imaging in patients with bladder cancer, although a major remaining pitfall is intense FDG accumulation in the urine.

Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations.

This paper applies and evaluates an automatic mutual information-based registration algorithm across a broad spectrum of multimodal volume data sets. The algorithm requires little or no pre-processing, minimal user input and easily implements either affine, i.e. linear or thin-plate spline (TPS) warped registrations. We have evaluated the algorithm in phantom studies as well as in selected cases where few other algorithms could perform as well, if at all, to demonstrate the value of this new method. Pairs of multimodal gray-scale volume data sets were registered by iteratively changing registration parameters to maximize mutual information. Quantitative registration errors were assessed in registrations of a thorax phantom using PET/CT and in the National Library of Medicine's Visible Male using MRI T2-/T1-weighted acquisitions. Registrations of diverse clinical data sets were demonstrated including rotate-translate mapping of PET/MRI brain scans with significant missing data, full affine mapping of thoracic PET/CT and rotate-translate mapping of abdominal SPECT/CT. A five-point thin-plate spline (TPS) warped registration of thoracic PET/CT is also demonstrated. The registration algorithm converged in times ranging between 3.5 and 31 min for affine clinical registrations and 57 min for TPS warping. Mean error vector lengths for rotate-translate registrations were measured to be subvoxel in phantoms. More importantly the rotate-translate algorithm performs well even with missing data. The demonstrated clinical fusions are qualitatively excellent at all levels. We conclude that such automatic, rapid, robust algorithms significantly increase the likelihood that multimodality registrations will be routinely used to aid clinical diagnoses and post-therapeutic assessment in the near future.

Untreated lung cancer: quantification of systematic distortion of tumor size and shape on non-attenuation-corrected 2-[fluorine-18]fluoro-2-deoxy-D-glucose PET scans.

The authors quantitatively evaluated possible distortions of tumor size and shape introduced on non-attenuation-corrected 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scans obtained in primary lung cancer tumors. Primary lung cancer tumors in 21 patients were measured on x-ray computed tomography (CT), attenuation-corrected FDG PET, and non-attenuation-corrected FDG PET scans. Apparent anteroposterior tumor dimensions on non-attenuation-corrected FDG PET scans were significantly larger (P = .0007; mean difference, 30%) than on attenuation-corrected FDG PET or CT scans (P = .05; mean difference, 28%). Left-to-right tumor dimensions on non-attenuation-corrected FDG PET scans were significantly smaller than on attenuation-corrected FDG PET scans (P = .03; mean difference, 8.5%) but were not significantly different from those on CT scans (P = .3).