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A 31-year-old man with a vagal nerve stimulator for seizure control was noted to have decreased metabolism within the thalamus as visualized by F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). Some investigators think the thalamus plays an important role in the regulation of seizure activity. Vagal nerve stimulation (VNS) may reduce thalamic activity, which in turn may reduce seizure activity. However, because the thalamus has diffuse connections throughout the brain, its role in seizure activity is likely complex. Observing decreased thalamic activity during VNS is just 1 small step toward understanding this role.

Purpose: The use of whole-body PET for re-staging of renal cell carcinoma has not been investigated. The aim of the current study was to examine the diagnostic accuracy and clinical usefulness of whole-body PET imaging for re-staging of renal cell cancer., Patients and Methods: Clinical PET was performed for re-staging in 36 patients with advanced renal cell cancer. Written reports of imaging studies (including CT, MRI, US, plain film and bone scan), patient history, and extensive chart notes were used to define the clinical stage before PET (pre-PET stage). The written PET report was used to define the clinical stage after PET (PET stage). Reports were used to determine the accuracy of PET for re-staging renal cell cancer and for defining biopsy proven lesions. Clinical parameters and biopsy proven lesions served as reference for the accuracy of PET for re-staging renal cell cancer., Results: PET classified the clinical stage correctly in 32/36 patients (89%) and was incorrect in 4/36 (11%) (sensitivity and specificity: 87% and 100%). In 20 patients, 25 suspicious lesions were biopsied within 3.2 +/- 6.7 months of the PET study. Of these, 17 were malignant and 8 were benign. PET correctly classified 21/25 (84%) of the biopsied lesions (sensitivity and specificity: 88% and 75%)., Conclusion: PET re-stages renal cell cancer with a diagnostic accuracy of 89%. Its diagnostic accuracy for classifying biopsy proven anatomic lesions as malignant or benign was 84%. These findings suggest that PET is useful in characterizing anatomic lesions of unknown significance in patients with renal cell cancer.

Context: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined., Objective: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia., Design, Setting, and Patients: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000., Main Outcome Measures: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses., Results: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001)., Conclusion: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Positron emission tomography (PET) is a biochemical-imaging tool that uses the uptake of the glucose analog 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) to detect head and neck tumor proliferation. The aim of this study is to determine if quantitation of either primary tumor metabolic activity or tumor response using PET scans could predict local control and overall survival in patients with head and neck cancer undergoing primary radiotherapy. Twelve patients with squamous cell carcinomas of the head and neck underwent PET scans before and 6 weeks after completion of radiation therapy. Tumor metabolic activity was quantitated using the metabolic ratio method. Mean follow-up was 40 months (range: 18-55 months). In our series, tumors with metabolic rates greater than that of the cerebellum are associated with significantly better local control (p < 0.05) and survival. Posttreatment PET imaging was falsely positive in one patient with clinical signs of severe inflammation. Tumors with greater than 50% decrease in metabolic activity with irradiation had improved local control. Clinically, nine patients had excellent response to irradiation. These results suggest that pretreatment PET findings may have prognostic implications in determining which patients will achieve long-term local control with primary radiation therapy. This may help identify those at increased risk of recurrence that may benefit from more aggressive altered fractionation schemes or combined modality therapy.

Unlabelled: Receiver operating characteristic (ROC) and localization ROC (LROC) studies were performed to compare lesion detection at the borderline of detectability on images reconstructed with two-dimensional filtered backprojection (FBP) without attenuation correction (a common clinical protocol), three-dimensional FBP without attenuation correction, two-dimensional FBP with segmented attenuation correction and a two-dimensional iterative maximum a posteriori (MAP) algorithm using attenuation correction. Lung cancer was the model for the study because of the prominent role of 18F-fluorodeoxyglucose PET in the staging of lung cancer and the importance of lesion detection for staging., Methods: Simulated lung cancer lesions were added to two-dimensional and three-dimensional PET data from healthy volunteers. Data were reconstructed using the four methods. Four nuclear medicine physicians evaluated the images. Detection performance with each method was compared using ROC and LROC analysis. Jackknife analysis provided estimates of statistical significance for differences across all readers for the ROC results., Results: ROC and LROC results indicated statistically significant degradation in detection performance with three-dimensional acquisition (average area under ROC curves [Az] 0.51; average area under LROC curves [A(z,LROC)] 0.13) and segmented attenuation correction (average Az 0.59; average Az,LROC 0.29) compared with two-dimensional FBP without attenuation correction (average Az 0.79; average A(z,LROC) 0.54). ROC and LROC results indicated an improvement in detection performance with iterative MAP reconstruction (average Az 0.83; average A(z,LROC) 0.64) compared with two-dimensional FBP reconstruction; this improvement was not statistically significant., Conclusion: Use of segmented attenuation correction or three-dimensional acquisition with FBP reconstruction is not expected to improve detection of lung lesions on whole-body PET images compared with images with two-dimensional FBP without attenuation correction. The potential improvement in detection obtained with an iterative MAP reconstruction method is small compared with that obtained with two-dimensional FBP without attenuation correction.

Purpose: We compare the detection of metastatic disease by helical computerized tomography (CT), positron emission tomography (PET) with F-18 fluorodeoxyglucose and monoclonal antibody scan with 111indium capromab pendetide in patients with an elevated prostate specific antigen (PSA) after treatment for localized prostate cancer., Materials and Methods: A total of 45 patients with an elevated PSA (median 3.8 ng./ml.) were studied following definitive local therapy with radical prostatectomy in 33, radiation therapy in 9 and cryosurgery in 3. CT of the abdomen and pelvis, and whole body PET were performed in all patients, of whom 21 also underwent monoclonal antibody scan. Lymph nodes 1 cm. in diameter or greater on CT were considered abnormal and were sampled by fine needle aspiration in 12 patients., Results: PET and CT were positive for distant disease in 50% of 22 patients with PSA greater than 4, and in 4 and 17%, respectively, of 23 with PSA less than 4 ng./ml. The detection rate for metastatic disease was similar for CT and PET, and higher overall than that for monoclonal antibody scan. Monoclonal antibody scan was true positive in only 1 of 6 patients, while PET was true positive in 6 of 9 with CT guided fine needle aspiration proved metastases., Conclusions: CT and PET each detected evidence of metastatic disease in 50% of all patients with a high PSA or PSA velocity (greater than 4 ng./ml. or greater than 0.2 ng./ml. per month, respectively). Both techniques are limited for detecting metastatic disease in patients with a low PSA or PSA velocity. Our data suggest that monoclonal antibody scan has a lower detection rate than CT or PET.

Background: Detection of myocardial viability is important in patients with ischemic cardiomyopathy. Restoration of blood flow to viable myocardium is associated with improved left ventricular function and improved patient prognosis. However, the prevalence of viable myocardium in patients with ischemic cardiomyopathy is unknown., Methods and Results: To determine the prevalence of myocardial viability, clinical [13N]ammonia/18F-deoxyglucose PET studies performed in 283 patients (age, 63+/-10 years) with ischemic heart disease (mean ejection fraction, 26+/-8%) were visually analyzed for the presence and extent of viable and nonviable myocardium. The myocardium was divided into 19 segments. The extent of viable myocardium was considered "functionally" significant if >/=5 segments ( approximately 25% of the left ventricular myocardium) exhibited a blood flow/metabolism mismatch and "prognostically" significant if 1 to 4 left ventricular segments did so. Of all patients, 41% had no evidence of viable myocardium, 55% had viable myocardium, and 4% had normal blood flow and metabolism within an enlarged left ventricle. Functionally significant viability was found in 27% and prognostically significant viability in 28% of the patients. Multivariate analysis revealed the presence of angina to be the only clinical parameter associated with the presence of functionally significant viability., Conclusions: Revascularization might improve patient prognosis in 55% and result in improved left ventricular function in 27% of all patients with ischemic cardiomyopathy.

Unlabelled: Several tracer kinetic methods have been proposed for quantification of regional myocardial blood flow (MBF) with 13N-ammonia and PET. Merits and limitations specific to each approach, however, generally are not clear, because they have not been evaluated in the same experimental environment. Therefore, we compared six different commonly used methods (11 modifications) to characterize the accuracy of each approach. The methods included the two-parameter model (method 1), the modified two-parameter model (method 2), the four-parameter model (method 3), the graphical analysis (method 4), the first-pass extraction method (method 5) and the dose uptake index (DUI; method 6)., Methods: Eleven studies in four dogs, 16 studies in eight healthy human volunteers and 14 studies in seven patients were performed using 13N-ammonia and PET. MBF in dogs was varied with dipyridamole and coronary occlusions and was measured independently and simultaneously with microspheres. Volunteers and patients were studied at baseline and after dipyridamole. MBF and DUI were estimated using a time-activity curve (Qi[t]) derived from dynamic images and regions of interest (ROls) and using the six methods. DUI was defined as Qi(t = 2 min) x weight/dose., Results: MBF estimated by methods 1-5 correlated well with microsphere MBF in dogs. MBF estimates by method 1 correlated well with those by methods 2, 4 and 5 and to a lesser degree with those by method 3 in both dog and human studies. DUI correlated poorly with MBF by microspheres and by methods 1-5 in both dog and human studies. MBF estimates by method 3 showed larger dispersion (SD/mean flow) and higher sensitivity to metabolites correction in arterial blood than those by methods 1, 2, 4 and 5., Conclusion: MBF can be measured accurately using 13N-ammonia PET and tracer kinetic methods. DUI is a poor indicator of MBF values. The results indicate that preference should be given to the two-parameter model, incorporating geometrical ROI representation (method 2) among the compartment models, and to the graphical analysis (method 4) among the noncompartmental approaches.

Objectives: The purpose of this study was to evaluate the predictive accuracy of positron emission tomography (PET) blood flow-F-18 fluorodeoxyglucose (FDG) imaging in coronary artery disease (CAD) patients with diabetes mellitus (DM)., Background: Positron emission tomography accurately predicts the postrevascularization improvement in left ventricular dysfunction in unselected patients with CAD. In diabetic patients, however, poor myocardial glucose utilization may limit the accuracy of the approach., Methods: Forty patients (64+/-10 years old; 19 with DM = group I; 21 without DM = group II) with reduced left ventricular ejection fraction (LVEF = 29+/-6%) were studied with N-13 ammonia and FDG PET before coronary revascularization. Studies were performed after intravenous injection of regular insulin (group I) or oral glucose administration (group II). Blood flow-FDG mismatches and matches were identified by polar map analysis in the three vascular territories of the left anterior descending, left circumflex and right coronary artery. Wall motion and LVEF were assessed by two-dimensional echocardiography before and 158+/-123 days after revascularization., Results: Of 107 vascular territories analyzed, 46 were classified as mismatch, 29 as match and 32 as normal. The FDG image quality, assessed by F-18 myocardium to blood pool activity ratios, and the predictive accuracy were similar in both groups; presence of a blood flow/FDG mismatch had a sensitivity of 92% (group I) and 94% (group II) and a specificity of 85% (group I) and 79% (group II) for an improvement in regional left ventricular function. A postrevascularization improvement in global left ventricular function was related to the extent of blood flow/FDG mismatch; LVEF increased from 30+/-7% to 35+/-7% (p = 0.017) in patients with one mismatch and from 27+/-4% to 41+/-7% (p < 0.001) in those with two mismatches., Conclusions: The predictive accuracy of blood flow/FDG imaging is maintained in patients with DM when a clinically acceptable study protocol, which guarantees good FDG image quality, is used. The extent of a blood flow/metabolism mismatch is correlated with the magnitude of the postrevascularization improvement in global left ventricular function.

Despite the large number of women with breast cancer and the importance of this disease in health care, only a relatively small number of published reports involve the application of 18-fluorodeoxyglucose (FDG) in the evaluation of patients with breast cancer. This report summarizes the results of these studies, presents the opinions from various clinical oncologists from both a university and community setting, and discusses the possible future implication of positron imaging technology in the management of breast cancer. The four potential areas of clinical application include (1) detection and differentiation of primary breast lesions, (2) staging of axillary lymph nodes, (3) detection of residual and metastatic disease, and (4) monitoring the response to chemotherapy.

The usefulness of positron-emission tomography (PET) for noninvasive assessment of several biological parameters of neoplastic tissue has been reviewed. Numerous radiotracers have been developed, whose particular distribution in the presence of cancer in vivo serves to distinguish medically relevant properties of the tumor cells with which they associate. That distribution is most accurately determined through use of a PET scanner, to localize and quantify the tracer molecules, in which have been incorporated positron-emitting isotopes. These tracers include hypoxia markers, receptor ligands, substrates for enzymatic modification by the products of expression of specific genes, and precursors of protein anabolism and carbohydrate catabolism. In addition, application of PET to evaluation of patients with some particular cancers has been examined, while placing special emphasis on the level of scientific rigor of the evidence underlying conclusions about appropriate use of PET in oncology., (Copyright 1998 W.B. Saunders Company.)

Unlabelled: The mouse model is currently being explored for various applications with PET imaging. Low resolution of current animal scanners relative to mouse size leads to difficulty in quantitating data from mouse PET images. We have, therefore, investigated methods for determining blood time-activity curves (TACs) from mouse PET studies done with fluorine-18-fluorodeoxyglucose (FDG)., Methods: Eight mice were fasted, the tail vein was injected with 150-300 microCi of FDG and dynamic images were acquired with a CTI/Siemens (Knoxville, TN) animal tomograph for 64.5 min. Concurrently, 11-14 left ventricle (LV) blood samples were drawn directly from the LV chamber. Organ TACs were obtained by drawing circular regions of interest (ROIs) of various sizes on images of the heart, liver and brain. For each mouse, the FDG model parameter K = (K1 x k3)/(k2 + k3) was estimated by a Patlak algorithm with various estimates of the blood TAC and, as a reference tissue TAC, the brain TAC., Results: Most partial-volume-corrected heart ROI TACs overestimated the LV samples. Blood TACs from heart images produced statistically different estimates of K than did the LV samples. The liver image-derived blood TACs yielded estimates of K that were comparable to those yielded by the LV samples. Estimates of K determined with two directly sampled LV points in conjunction with the liver image-derived TAC were not statistically different from the estimates obtained with the LV samples. The size and location of ROIs on images of the liver minimally affected the TACs., Conclusion: We have shown that it is experimentally possible to obtain a blood TAC from mouse studies by repeatedly sampling from the LV. We have also shown that images of the liver can be used to reliably estimate the blood TAC. Future FDG PET studies with the mouse model will benefit from this demonstrated ability to noninvasively quantitate blood TACs directly from FDG PET images.

Purpose: Early experience has shown that positron-emission tomography (PET) is a useful technique for the detection of occult squamous cell carcinoma of the head and neck. Although highly sensitive, PET lacks definition of anatomic detail and therefore does not localize pathology precisely. To circumvent this limitation, a computerized coregistration technique has been developed at the University of California-Los Angeles to correlate PET and magnetic resonance images (MRI). This method allows accurate, precise anatomic localization of areas of heightened glucose metabolism, including subclinical tumors., Materials and Methods: The technique uses a coregistration computer program that precisely superimposes the PET scan with the corresponding MRI image., Results: Two cases are presented in which PET-MRI coregistration was used to anatomically define the areas of heightened glucose metabolism. Large tumors were selected because the precision of the method can be verified., Conclusion: The coregistration technique is a valuable addition to PET imaging, particularly in its ability to anatomically localize PET findings. The most important application of this technique is to facilitate the biopsy of subclinical lesions identified on PET.

Unlabelled: This study assessed the diagnostic accuracy of whole-body PET on a patient and lesion basis using 18F-fluorodeoxyglucose (FDG) for the detection of tumor foci in patients with suspected recurrent or metastatic lesions of breast carcinoma., Methods: Whole-body FDG-PET imaging was performed on 57 patients with a previous history of breast carcinoma who were referred for a clinical suspicion of disease recurrence. Whole-body PET images were scored from 1 (definitely negative) to 5 (definitely positive) by three independent observers, and discrepancies were resolved by a fourth observer. Patients were clinically followed for up to 24 mo to assess the accuracy of PET diagnosis by biopsy, follow-up imaging and other diagnostic tests., Results: PET scans showed that there were 41 sites indicating recurrent or metastatic disease in 29 patients. There were 38 sites in 28 patients that showed no evidence for malignant disease. On a patient basis, with scores 4 or 5 considered to be positive, sensitivity and specificity were 93% and 79%, respectively. The corresponding positive and negative predictive values were 82% and 92%. On a lesion basis, with scores 4 or 5 considered to be positive, the sensitivity was 85% and specificity 79%. The area index in receiver operating characteristic analysis was 0.91 for patient-based analysis and 0.88 for lesion-based analysis. To determine the cause for false-negative and false-positive findings more precisely, false-negative lesions with scores of 3 or lower and false-positive lesions with scores of 4 or higher were analyzed. Bone metastases had a significantly larger proportion of false-negative lesions than other nonosseous malignant sites (p < 0.05). False-positive lesions were due to muscle uptake (n = 5), inflammation (n = 4), blood pool activity in the great vessels (n = 2), bowel uptake (n = 1) and unknown causes (n = 6)., Conclusion: The whole-body FDG-PET scan is a useful diagnostic test for detecting recurrent or metastatic lesions of breast carcinoma. However, the sensitivity for metastases to bone appears to be lower than that to other organs. Specificity may be improved by more strict attention to patient preparation and better recognition of physiologic skeletal muscle or artifactual uptakes.

Purpose: We provide scientists and clinicians with an introduction to the basic principles and methods of positron emission tomography (PET) and summarize the recent research and clinical applications of PET in the urological field. Specifically, we introduce PET so that the reader can understand and objectively review current and future articles that involve this imaging technology., Materials and Methods: The recent applications of PET in urology in the published literature were searched and reviewed., Results: In prostate carcinoma preliminary studies using radiotracer 18-fluoro-2-deoxyglucose (FDG) demonstrated that PET cannot reliably differentiate between primary prostate cancer and benign prostatic hyperplasia, and that PET is not as sensitive as bone scintigraphy for the detection of osseous metastases. However, PET may have a role in the detection of lymph node metastases in patients with prostate specific antigen relapse after primary local therapy. In renal cell carcinoma recent studies have shown the ability of FDG PET to detect primary and metastatic lesions and to monitor response to therapy. In the staging of testicular cancer FDG PET has been used to differentiate viable carcinoma from benign teratomas and/or fibrotic or necrotic changes., Conclusions: Current developments in PET technology that accurately stage the extent of tumor before surgery as well as monitor effectiveness or ineffectiveness of new or current therapies may make PET a valuable tool in research and in the management of urological diseases.

Early diagnosis in oncology is important for treatment by surgical intervention, which generally has the highest curative potential. For higher stages of disease involvement, initiation of rapid treatment is indicated to provide the patient with the optimal therapy regimen. Although this may not improve the prognosis, it will maintain the quality of life. Anatomic imaging modalities, such as CT, MR imaging, and US, are clinically important high-resolution imaging techniques that are well suited to reveal structural abnormalities. However, the differentiation of lesions as being benign or malignant is still problematic. Metabolic imaging modalities in nuclear medicine (NM), i.e., single photon emission computed tomography (SPECT) and positron emission tomography (PET), can reveal biochemical parameters of the lesions such as glucose, oxygen, or amino acid metabolism, or measure the receptor density status. These parameters may allow a completely new clinical perspective in the management and understanding of diseases such as cancer. Although PET has been around since the early 1960s, it has only recently emerged as a powerful diagnostic tool in oncology. Society has great difficulty accepting this clinical imaging modality because of its high cost and complexity. Current applications of PET in oncology have been in characterizing lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and therapy monitoring. Here, the role of PET in diagnosis, staging, and restaging of cancer is reviewed and compared with the other tumor imaging modalities. We cover articles published in the past 3 years. We utilize the typical radiology format, in which the contribution in each body area is reviewed (topographic orientation), instead of the more organ-based approach used in internal medicine.

Medical imaging technology is rapidly expanding and the role of each modality is being redefined constantly. PET has been around since the early sixties and gained clinical acceptance in oncology only after an extreme number of scientific publications. Although PET has the unique ability to image biochemical processes in vivo, this ability is not fully used as a clinical imaging tool. In this overview, the role of PET in relation to other tumor imaging modalities will be discussed and the reported results in the literature will be reviewed. In predicting the future of PET, technical improvements of other imaging modalities need to be dealt with. The fundamental physical principles for image formation with computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), photon-emission tomography (PET), and single photon emission CT (SPECT) will not change. The potential variety of radiopharmaceuticals which may be developed is unlimited, however, and this provides nuclear imaging techniques with a significant advantage and adaptive features for future biologic imaging. The current applications of PET in oncology have been in characterizing tumor lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and monitoring therapy. The future developments in medicine may use the unique capabilities of PET not only in diagnostic imaging but also in molecular medicine and genetics. The articles discussed in this review were selected from a literature search covering the last 3 years, and in which comparisons of PET with conventional imaging were addressed specifically. PET studies with the glucose analogue fluorine-18-labeled deoxyglucose (FDG) have shown the ability of detecting tumor foci in a variety of histological neoplasms such as thyroid cancer, breast cancer, lymphoma, lung cancer, head and neck carcinoma, colorectal cancer, ovarian carcinoma, and musculoskeletal tumors. Also, the contribution of the whole body PET (WBPET) imaging technique in diagnosis will be discussed. In the current health care environment, a successful imaging technology must not only change medical management but also demonstrate that those changes improve patient outcome.

Unlabelled: Accurate staging of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) is important for treatment management. In this study, the utility of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) whole-body PET was evaluated as an imaging modality for initial staging or restaging of 7 HD and 11 NHL patients., Methods: Whole-body PET-based staging results were compared to the patient's clinical stage based on conventional staging studies, which included combinations of CT of the chest, abdomen and pelvis, MRI scans, gallium scans, lymphangiograms, staging laparatomies and bone scans., Results: Accurate staging was performed in 17 of 18 patients using a whole-body PET-based staging algorithm compared to the conventional staging algorithm in 15 of 18 patients. In 5 of 18 patients, whole-body PET-based staging showed additional lesions not detected by conventional staging modalities, whereas conventional staging demonstrated additional lesions in 4 of 18 patients not detected by whole-body PET. The total cost of conventional staging was $66,292 for 16 CT chest scans, 16 CT abdominal/pelvis scans, three limited MRI scans, four bone scans, five gallium scans, two laparotomies and one lymphangiogram. In contrast, scans cost $36,250 for 18 whole-body PET studies and additional selected correlative studies: one plain film radiograph, one limited CT, one bone marrow scan, one upper GI and one endoscopy., Conclusion: A whole-body FDG-PET-based staging algorithm may be an accurate and cost-effective method for staging or restaging HD and NHL.

Unlabelled: The extraction of pure arterial time-activity curves (TACs) from dynamic PET images of a small animal heart using factor analysis of dynamic structures (FADS) was found to be unsuccessful due to the small size of the cardiac chamber that causes extensive mixture of TACs of different structures., Methods: In this study, we used digital phantoms of the left ventricle (LV cavity size: 1-2 cm) and small monkey (LV cavity size: approximately 2 cm) dynamic FDG PET studies to evaluate FADS for extracting the pure blood-pool TACs by adding a single blood sample (taken at a late scan time) constraint., Results: In the digital phantom studies, spillover fractions in the extracted blood-pool TACs using FADS without a blood sample constraint (FADS(-)) and with a blood sample constraint (FADS(+)) were 3%-91% and < 3%, respectively. In the monkey studies (n = 4), FADS(+) extracted blood-pool TACs matched well with the arterialized well counter measurements (% differences of curve integration; FADS(-) < 82%; FADS(+) < 9%). The microparameters (K1*, k2*, k3*, k4*) and macroparameters (Knlr), obtained from the FADS(+) blood-pool TACs, were similar to those obtained from plasma samples in a three-compartment model fitting (% differences of Knlr:phantom studies < 5%; monkey studies < 9%)., Conclusion: The FADS technique with a single-blood sample has the potential to extract the pure blood-pool TACs directly from dynamic PET images of a small animal without multiple blood sampling, region of interest definition or spillover correction.

Unlabelled: Preliminary studies have shown that PET is more accurate than CT for the staging of non-small-cell lung carcinoma (NSCLC). However, the potential effect of PET on the management of these patients and its cost-effectiveness has not been rigorously studied. Thus, we have used decision tree sensitivity analysis to assess the cost-effectiveness of a PET based strategy for staging of NSCLC., Methods: Two decision strategies for selection of potential surgical candidates were compared; thoracic CT alone or thoracic CT and thoracic PET. The first decision tree was conservatively constructed by requiring mediastinoscopy (biopsy) to confirm imaging results so that no patient with surgically curable disease would miss the opportunity for surgery in either strategy. A second less conservative tree in which only nonconcordant results are biopsied was also tested. The various paths of each strategy are dependent on numerous parameters which were determined from a review of the medical literature. Life expectancy was calculated using the declining exponential approximation of life expectancy and reduced based on procedural mortality. Costs were based on mean costs at our institution. For all possible outcomes of each strategy, the expected cost and projected life expectancy were determined. The effect of changing one or more parameters on the expected cost and life expectancy were studied using a sensitivity analysis., Results: The CT + PET strategy in the conservative decision tree showed a saving of $1154 per patient without a loss of life expectancy (increase of 2.96 days) as compared to the alternate strategy of CT alone. Both these effects were the result of improved staging of lung carcinoma prior to the decision for surgery. The CT + PET strategy in the less conservative decision tree showed a savings of $2267 per patient but misses 1.7% of potentially operable patients., Conclusion: These results show through rigorous decision tree analysis, the potential cost-effectiveness of using FDG PET in the management of NSCLC. These results form a basis for detailed study of the results obtained from multicenter trials on the accuracy of PET in NSCLC management. Furthermore, the techniques utilized for decision tree analysis have broad range of applicability to the entire field of nuclear medicine.

Background: [13N]Ammonia has been validated in dog studies as a myocardial blood flow tracer. Estimates of myocardial blood flow by [13N]ammonia were highly linearly correlated to those by the microsphere and blood sample techniques. However, estimates of myocardial blood flow with [13N]ammonia in humans have not yet been compared with those by an independent technique. This study therefore tested the hypothesis that the [13N]ammonia positron emission tomographic technique in humans gives estimates of myocardial blood flow comparable to those obtained with the [15O]water technique., Methods and Results: A total of 30 pairs of positron emission tomographic flow measurements were performed in 30 healthy volunteers; 15 volunteers were studied at rest and 15 during adenosine-induced hypermia. Estimates of average and of regional myocardial blood flow by the [13N]ammonia and the [15O]water approaches correlated well (y = 0.02 + 1.02x, r = .99, P < .001 SEE = 0.023 for average and y = 0.06 + 1.00x, r = .97, P < .001, SEE = 0.025 for regional values) over a flow range of 0.45 to 4.74 mL.min-1.g-1. At rest, mean myocardial blood flow was 0.64 +/- 0.09 mL.min-1.g-1 for [13N]ammonia and 0.66 +/- 0.12 mL.min-1.g-1 for [15O]water (P = NS). For adenosine-induced hyperemia, mean myocardial blood flow was 2.63 +/- 0.75 mL.min-1.g-1 for [13N]ammonia and 2.73 +/- 0.77 mL.min-1.g-1 for [15O]water (P = NS). The coefficient of variation as an index of the observed heterogeneity of myocardial blood flow averaged, for [13N]ammonia, 9 +/- 4% at rest and 12 +/- 7% during stress and, for [15O]water, 14 +/- 11% at rest and 16 +/- 9% during stress. The coefficients of variation for [15O]water were significantly higher than those for [13N]ammonia (P = .004 at rest and P = .03 during stress)., Conclusions: The two approaches yield comparable estimates of myocardial blood flow in humans, which supports the validity of the [13N]ammonia method in human myocardium previously shown only in animals. However, the [15O]water approach reveals a greater heterogeneity (presumably method-related), which might limit the accuracy of sectorial myocardial blood flow estimates in humans.

Unlabelled: We developed a method to improve the quantitative precision of FDG-PET scans in cancer patients. The total-lesion evaluation method generates a correlation coefficient (r) constrained Patlak parametric image of the lesion together with three calculated glucose metabolic indices: (a) the total-lesion metabolic index ("KT-tle", ml/min/lesion); (b) the total-lesion voxel index ("VT-tle", voxels/lesion); and (c) the global average metabolic index ("KV-tle", ml/min/voxel)., Methods: The glucose metabolic indices obtained from conventional region of interest (ROI) and multiplane evaluation were used as standards to evaluate the accuracy of the total-lesion evaluation method. Computer simulations and four patients with metastatic melanoma before and after chemotherapy were studied., Results: Computer simulations showed that the total-lesion evaluation method has improved precision (% s.d. < 0.6%) and accuracy (approximately 10% error) compared with the conventional ROI method (% s.d. approximately 5%; approximately 25% error). The KT-tle and VT-tle indices from human FDG-PET studies using the total-lesion evaluation method showed excellent correlations with the corresponding values obtained from the conventional ROI methods and multiplane evaluation (r approximately 1.0) and CT lesion volume measurements., Conclusion: This method is a simple but reliable way to quantitatively monitor tumor FDG uptake. The method has several advantages over the conventional ROI method: (a) less sensitive to the ROI definition, (b) no need for image registration of serial scan data and (c) includes tumor volume changes in the global tumor metabolism.

Unlabelled: In this study, factor analysis of dynamic structures (FADS) was used to extract the "pure" blood-pool time-activity curves (TACs) and to generate parametric myocardial blood flow (MBF) images (pixel unit: ml/min/g)., Methods: Ten dynamic 13N-ammonia dog PET studies (three baseline, five hyperemia and two occlusion) were included. Three factors (TACs) and their corresponding factor images (the right ventricular and left ventricular blood pools and myocardial activities) were extracted from each study. The left ventricular factors matched well with the plasma TACs. The factor images of myocardium were then converted to a parametric images of MBF using a relationship derived from a two-compartment model., Results: MBF estimates obtained from FADS correlated well with MBF estimates obtained with the two-compartment model (r = 0.98, slope = 0.84) and microsphere techniques (r = 0.96, slope = 0.94). FADS-generated MBF parametric images have better image quality and lower noise levels compared to those generated with Patlak graphical analysis., Conclusion: Regional MBF can be measured accurately and noninvasively with 13N-ammonia dynamic PET imaging and FADS. The method is simple, accurate and produces parametric images of MBF without requiring blood sampling and spillover correction.

Unlabelled: Arterial sampling in dynamic PET studies can be eliminated by using left ventricular or aortic time-activity curves (TAC) obtained from user drawn regions of interest (ROIs) after appropriate spillover correction. In this study, we evaluated the feasibility of extracting the "pure" arterial TAC from dynamic PET images using factor analysis of dynamic structures (FADS)., Methods: Computer simulations were used to study the performance of the FADS algorithm with positivity constraints. Ten canine 13N-ammonia and two human FDG-PET dynamic studies were used to extract the blood TACs from FADS. Plasma samples and compartmental model fittings were used to validate the accuracy of the FADS-generated blood factors., Results: We found that FADS with positivity constraints was sufficient to extract the blood factor from the composite dynamic images. The "pure" blood-pool TACs that matched well with the arterialized well counter measurements were generated from FADS in the canine and human studies., Conclusion: FADS has the potential to accurately extract "pure" blood TAC from dynamic PET images, allowing reliable quantitation of biological information from PET studies without blood sampling, ROI drawing or spillover correction.

Unlabelled: To evaluate the effects of hematopoietic cytokines on bone marrow glucose metabolism noninvasively, we studied serial quantitative FDG-PET images in 18 patients with metastatic melanoma and normal bone marrow who were undergoing granulocyte-macrophage colony-stimulating factor (GMCSF) or macrophage colony-stimulating factor (MCSF) administration as an adjunct to chemotherapy., Methods: All patients received 14 days of cytokine therapy in three groups: four patients were treated with GMCSF (5 micrograms/kg/d SQ), eight patients were treated with GMCSF (5 micrograms/kg/d SQ) and monoclonal antibody (MAbR24) and six patients were treated with MCSF (80 micrograms/kg/d IVCI) and MAbR24. Dynamic FDG-PET imaging was performed over the lower thoracic or upper lumbar spine at four time points in each patient., Results: Baseline glucose metabolic rates in the bone marrow of these three groups of patients were similar (5.2 +/- 0.7, 4.4 +/- 0.8 and 4.8 +/- 1.2 micrograms/min/g as mean value and standard deviations, respectively). In both GMCSF and GMCSF + R24 groups, rapid increases in bone marrow glucose metabolic rates were observed during therapy. After GMCSF was stopped, bone marrow glucose metabolic rates rapidly decreased in both groups. The glucose metabolic response in these two groups was not significantly different by pooled t-statistics (p = 0.105). In the MCSF+R24 group, the increase of glucose metabolic rate on Days 3 and 10 was 35% and 31% above baseline on the average, but was not significant., Conclusion: The results support the use of parametric FDG-PET imaging for noninvasive quantitation of bone marrow glucose metabolic changes to hematopoietic cytokines in vivo.

Background: Coronary arteriography is considered the "gold standard" for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography., Methods and Results: We studied 28 subjects: 18 patients with coronary artery disease (66 +/- 8 years) and 10 age-matched healthy volunteers (64 +/- 13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non-infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4 +/- 0.4 versus 2.6 +/- 0.7, respectively; P = NS). Quantitative PET estimates of hyperemic blood flow (r = .81, P < .00001), flow reserve (r = .78, P < .00001), and an index of the "minimal coronary resistance" (r = .78, P < .00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4 +/- 0.4 versus 1.8 +/- 0.5, respectively; P = .04)., Conclusions: In patients with coronary artery disease, non-invasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.

Positron emission tomography (PET) has recently proved to be highly sensitive in detecting known extracranial head and neck squamous cell carcinomas when compared to computed tomography and magnetic resonance imaging (MRI). The ability of PET to detect early subclinical recurrent squamous cell malignancies in patients who received primary radiotherapy was evaluated. A new PET-MRI coregistration technique was used to determine precise anatomic tumor location, enabling directed biopsies to confirm the presence of malignancy, and to plan additional therapeutic strategies. Ten patients underwent PET evaluation with intravenous [18F]-fluorodeoxyglucose and received postradiotherapy MRI scans. In all cases, PET accurately detected the presence of recurrent disease despite negative or equivocal MRI scans and indeterminate clinical examinations. PET appears to be highly effective in detecting early recurrent head and neck squamous cell malignancies in postirradiated patients.

Positron emission tomography (PET) studies of cancer with the glucose analog 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) have emerged as both a useful research and clinical method for detecting (diagnosing), staging, and monitoring treatment responses in a variety of neoplasms, including tumors of the brain, head and neck, lung, breast, gastrointestinal and genitourinary systems, lymphatic system, musculoskeletal system, and other organ systems. In addition to FDG, many other positron emitting radiopharmaceuticals are under investigation and development in oncology, but the largest set of clinically relevant results to date has been acquired with FDG. Because most aggressive neoplasms have high glycolytic rates, neoplasms throughout the body may potentially be visualized with PET, using both standard transaxial imaging methods and techniques such as whole body PET imaging for surveying the entire body.

Background: The purpose of this study was to evaluate the utility of positron emission tomography- (PET) 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) imaging in extracranial head and neck cancers., Methods: Sixty patients with biopsy-proven cancers were studied using PET-FDG. Thirty-four patients were studied before therapy (staging), of which 15 patients received primary radiotherapy and serial PET-FDG imaging (monitoring). Seven patients with advanced disease had laser excision (monitoring), and 19 patients were evaluated for recurrent disease (recurrence)., Results: Four patients had unknown primary lesions. PET-FDG imaging located the primary tumor in two of four patients, and magnetic resonance imaging (MRI) in none of four. In the remaining patients (staging), PET-FDG imaging detected the primary tumor in 29 of 30 patients, and MRI in 23 of 30. In the staging group, PET-FDG imaging identified the presence or absence of lymph node involvement in 32 of 34 patients, and MRI in 31 of 34. PET-FDG imaging was helpful in evaluating tumor response to radiation therapy or laser excision. Ten patients evaluated for recurrent disease had biopsy-confirmed recurrences, and 7 had no recurrence. PET-FDG imaging results were positive for primary tumor recurrence in 9 of 10 patients, and MRI results were positive in 6 of 10. MRI results were negative for lymph node disease in one of these patients with recurrent primary tumor where PET-FDG imaging and biopsy demonstrated nodal involvement. PET-FDG results were negative for recurrent disease in seven of seven patients, and MRI results were negative for recurrent disease in in four of seven., Conclusion: In this series, the authors found that PET-FDG is a useful diagnostic modality for evaluating the patient with an unknown primary, monitoring response to therapy, and in detecting recurrent tumors.

Quantitative indexes based on regions of interest ratios from preoperative thallium-201 SPECT and F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans were compared for their ability to predict the histological grade of cerebral gliomas. Of the five different ratios used to determine the index for each PET scan, the ratio of tumour versus ipsilateral hemisphere in the same plane as the tumour showed the most significant correlation with glioma grade (p < 0.001). A large study of 62 thallium-201 SPECT scans showed equally good correlation with glioma grade (p < 0.0005). The use of thallium-201 SPECT for detection of tumour recurrence had 100% sensitivity in this series, while PET scans had 90.9% sensitivity. Patients with a rate of change in serial thallium indexes of 0.475 +/- 0.278 per month survived 5.93 +/- 2.25 months from onset of index increase, while those with little change in the index (0.069 +/- 0.063 per month) survived 17.93 +/- 5.25 months from onset of index increase. Results indicate thallium-201 SPECT correlates well with tumour grade and is equally efficient as PET in screening for glioma recurrence.

Positron emission tomography (PET) is an imaging technique that can produce high-quality tomographic images reflective of the metabolic characteristics of imaged tissue. Among the many positron-emitting tracers utilized in conjunction with PET is [18F]fluoride ion; it is actively taken up in bone in proportion to bone metabolic activity, analogous to standard nuclear medicine bone scanning agents such as technetium methylenediphosphonate ([99mTc]MDP). Whole-body imaging with PET and [18F]fluoride ion generates tomographic images that are useful in mapping patterns of bone metabolism, as well as identifying extraosseous site of bone formation or calcification. We report the case of a patient with polyostotic fibrous dysplasia, metastatic osteogenic sarcoma, and a breast mass, who presented with pulmonary nodules, in whom [18F] fluoride ion/PET imaging was useful in confirming the nature of the pulmonary nodules.

Positron emission tomography (PET) of the brain and heart has made important contributions in clinical and research applications in the fields of neurology and cardiology. The more recent applications of PET in tumor imaging has marked oncology as the next frontier in PET; however, the dilemma of rising health care cost will challenge the application of new technologies. This challenge can be approached by innovative and appropriate use of sophisticated technology in both the research and clinical realms. The current developments of PET imaging technology to accurately stage the extent of tumor, as well as monitor the effectiveness or ineffectiveness of new or current therapies will be an extremely valuable tool in research and in the cost effective management of cancer patients. In the future, the oncologist may be able to adjust the chemotherapy to the tumor response based on PET imaging. In other situations, PET may be able to predict that no existing therapy will elicit a durable response, resolving the patients' and families' uncertainty of whether extreme therapeutic measures would have made a significant difference. This paper reviews some of the recent developments and areas of research in tumor PET imaging, and describes some of the practical and technical aspects involved with FDG tumor quantitation and whole body PET imaging.

Purpose: To quantitate the changes induced in uptake of the glucose analog 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in normal structures in the head and neck and compare these to the change in uptake in malignant structures in patients with head and neck tumors undergoing radiation therapy., Materials and Methods: Eleven patients with biopsy-confirmed squamous cell carcinoma of the head and neck were studied before, during, and after a 6-week course of radiation therapy with positron emission tomography (PET)-FDG imaging. A ratio of FDG uptake in the structure compared with that in the cerebellum (termed metabolic ratio) within and outside of the field of radiation was determined in the adenoids; lingual and palatine tonsils; parotid, submandibular, and sublingual glands; and nasal turbinates, soft palate, and gingiva., Results: The average metabolic ratio in the tonsils, nasal turbinates, soft palate, and gingiva did not change significantly with treatment., Conclusion: FDG uptake in normal structures does not change with radiation therapy. This fact is in marked contrast to the FDG uptake in squamous cell carcinomas in the head and neck, which decrease dramatically with treatment (P < .005).

The utility of the mean transit time equation was investigated for estimation of the myocardial clearance rate constant of 11C-acetate, which is proportional to myocardial oxygen consumption rates. The mean transit time approach was also employed to generate parametric images of the clearance rate constant of 11C-acetate with dynamic PET imaging in 20 normal human studies. Input function delays and cutoff errors due to the truncation of the myocardial tissue time-activity curve at a finite time were corrected. The clearance rate constants estimated by mean transit time correlated well with the estimates by conventional monoexponential fitting (15 min (truncation time): Y = 0.01 + 0.94X, correlated coefficient (r) = 0.99; 16 min: Y = 0.03 + 0.94X, r = 0.98; 20 min: Y = 0.03 + 0.84X, r = 0.99). The clearance rate constants estimated by the mean transit time approach also correlated well (r = 0.94) with the measured rate-pressure products. The quality and noise level of parametric images of the clearance rate constants generated by mean transit time are improved over those generated by monoexponential fitting. Additional advantages of the mean transit time approach compared to the standard monoexponential fitting method for estimating myocardial clearance rate constant of 11C-acetate include ease of input function delay correction, less sensitivity to the shape of the input function and elimination of subjective data selection of the linear portion of the clearance data on a semilog plot. Thus, this approach is expected to facilitate objective quantitative analysis of indices of myocardial oxygen consumption.

Two types of image similarity measures, the sum of absolute differences (SAD) and the stochastic sign change (SSC), were compared for three-dimensional registration of images from PET. To test the accuracy of both registration methods, 30 FDG brain studies, 40 13N-ammonia cardiac studies and 20 FDG liver tumor studies (where each image set contained 15 image planes, 128 x 128 pixels per plane) were made into worse case conditions by creating image sets of low counts and extreme defects. These images were then registered to the reference images that had been moved in three dimensions into a random set of known translations, rotations and normalization factors (x, y, z, theta, rho, sigma, nf). Neither method required any external fiduciary markers or operator interventions to register a set of images. The optimization of the image similarity (using the SAD or SSC) was performed with the simplex method and registration was completed within 10 min of computation time on a low-end workstation. Overall, the SAD method had an average inplane (x, y) registration error of 0.5 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.5 +/- 0.4 degrees, an out-of-plane rotational error of 1.1 +/- 1.2 degrees and a normalization factor error of 0.015 +/- 0.016. The SSC method had an average inplane (x, y) registration error of 0.6 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.7 +/- 0.5 degrees, an out-of-plane rotational error of 1.0 +/- 1.2 degrees and a normalization factor error of 0.014 +/- 0.014. This study demonstrates that either the SAD or SSC method for measuring image similarity, combined with the simplex method for function optimization, are accurate methods for registration of a wide variety of PET images including low count studies and those with marked interval changes in the pattern of count distribution.

Patlak graphical analysis was applied to quantify renal cortical blood flow with N-13 ammonia and dynamic positron emission tomography. Measurements were made in a swine model of kidney transplantation with a wide range of normal and abnormal renal blood flows (N = 57 studies) and in 20 healthy human volunteers (N = 45 studies). Estimates of renal cortical blood flow by the Patlak method were compared to those from a two-compartment model for N-13 ammonia. In addition, estimates of renal cortical blood flow by the N-13 ammonia PET approach were compared in 10 normal human volunteers to estimates by the metabolically inert, freely diffusible O-15 water and a one-compartment model. Patlak graphical analysis estimates of renal cortical blood flow correlated linearly with the standard two-compartment model in pigs (y = -0.05 + 1.01x, r = 0.99) and in humans (y = 0.57 + 0.88x, r = 0.93). Estimates of renal cortical blood flow by O-15 water in human volunteers were also linearly correlated with those by N-13 ammonia and the Patlak graphical analysis (y = 0.71 + 0.84x, r = 0.86). Renal cortical blood flow estimates were highly reproducible both with N-13 ammonia and O-15 water measurements in humans. It is concluded that the Patlak graphical analysis with N-13 ammonia dynamic positron emission tomograpic imaging renders accurate and reproducible estimates of renal cortical blood flow. Moreover, the graphical analysis approach is 1,000 times faster than the standard model fitting approach and suitable for generating parametric images of renal blood flow in the clinical setting.

The existing means of detecting recurrent ovarian carcinoma are notoriously poor. Positron emission tomography (PET) is a form of computer-assisted imaging which produces images reflective of the biochemistry of the tissues rather than their physical characteristics. PET imaging with the positron emitting glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) exploits the accelerated rate of glycolysis characteristic of malignant tissue to image tumors. To begin to study PET's ability to diagnose recurrent ovarian cancer, whole-body PET FDG scanning was performed on 13 patients prior to planned surgical exploration. Seven patients were suspected of having recurrence based upon clinical findings, and 6 patients were clinically free of disease. In all 6 of the patients with suspected recurrence who subsequently underwent surgery, PET images demonstrated increased FDG uptake in a distribution that correlated with surgical-pathologic findings. Both intraperitoneal and extraperitoneal lesions were detected by PET. All 6 patients judged clinically free of disease had negative PET scans, but in 5 of these microscopic foci of residual tumor were found at surgery. Although PET FDG cannot replace surgery in the detection of microscopic recurrence, it can accurately detect tumors greater than 1.0 cm in diameter.

Purpose: Following radiation therapy, evaluation of viable tumor can often be difficult with anatomic imaging criteria (tumor size alone). In this study, the utility of biochemical imaging with the glucose analog 2-[F-18]fluoro-2-deoxy-D-glucose and positron emission tomography was investigated in patients treated with radiation therapy., Methods and Materials: Between 1990 and 1992, 19 patients were studied, including 15 patients with head and neck cancer, (4 oropharynx, 4 sinus, 3 larynx, 2 hypopharynx, 2 oral cavity [one patient], 1 nasopharynx), and 4 patients with breast cancer. Post-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose studies were done in all patients, with 9 head and neck patients receiving pre-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose scans as well. Results were correlated with other imaging techniques and pathology., Results: Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose detected head and neck primary tumors and lymph node metastases in all nine pre-radiation scans, while magnetic resonance imaging failed to detect two primary tumors. Serial positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed a significant decrease in tumor activity after radiation therapy, compared to pre-radiation levels, (p < 0.05), except for two patients with increased uptake at the primary site. Biopsies of these two patients showed persistent/recurrent disease after radiation therapy, which was not detected by magnetic resonance imaging. Six additional head and neck patients, with suspicious examination and inconclusive magnetic resonance imaging, were imaged with positron emission tomography after radiation therapy only. Five patients had increased positron emission tomography activity, with corresponding biopsies positive in four patients, and negative in one patient with clinically worsening symptoms. The remaining sixth patient had minimal and stable positron emission tomography uptake, and is improving clinically. Four patients had mammogram findings suspicious for recurrence after conservation treatment for breast cancer. Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed no focal activity in the breast in two patients, and increased activity in the area suspicious for recurrence in the other two patients. Biopsies correlated with positron emission tomography results., Conclusion: Changes and presence of positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose activity correlated with pathologic findings in head and neck and breast cancer patients in this series. In patients with elevated or rising positron emission tomography activity after radiation therapy, persistent or recurrent disease was found in 89% of patients, (8/9). Magnetic resonance imaging did not detect the head and neck recurrences, and mammography was suspicious in patients with both benign and malignant breast changes after radiation therapy. In addition, our data indicate that in head and neck patients with pre-radiation positron emission tomography scans, a significant decrease in activity should occur after radiation therapy, if local control is to be expected.

Objective: This study was done to determine the feasibility and potential utility of whole-body PET using the glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose (FDG) for the detection of primary malignancies and metastatic lesions., Materials and Methods: This was a prospective, nonrandomized study of whole-body FDG-PET imaging carried out at a large university teaching hospital in Los Angeles, CA, U.S.A. The study group consisted of all patients referred for PET imaging (87) with a suspected diagnosis of primary or recurrent malignancy and who had eventual histological confirmation of their lesions., Results: In the 87 patients, whole-body PET studies were positive (presence of focal FDG uptake relative to surrounding tissues uptake) in 61 of 70 patients (87%) with subsequent biopsy-confirmed primary or recurrent malignant lesions, including carcinomas of breast, lung, ovary, prostate, colon, urinary bladder, and gallbladder origin, as well as malignant melanoma, carcinoid, osteosarcoma, lymphoma, and spinal cord astrocytoma. The PET images revealed no focal hypermetabolism at the known site of tumor in patients with primary prostate carcinoma (two), microscopic ovarian carcinoma (two), breast carcinoma (one), low-grade carcinoid tumors (two), and one patient with recurrent microscopic osteogenic sarcoma. The PET studies detected the primary lesion in 15 of 17 patients with breast carcinoma and in 6 of 6 patients with primary lung carcinoma. Of the 17 patients with benign biopsies, 13 patients had FDG-PET studies without focal areas of uptake., Conclusion: Because of the high glycolytic rate of malignant tissue, the whole-body FDG-PET technique has promise in the detection of a wide variety of both primary and metastatic malignancies. The presence of FDG uptake in benign inflammatory conditions may limit the specificity of the technique. The sensitivity for the detection of malignant lesions was 87% and the positive predictive value was 94%. The whole-body FDG-PET method is promising both in determining the nature of a localized lesion and in defining the systemic extent of malignant disease.

Background: The clinical staging and management of both primary and metastatic lung lesions depends on accurate imaging techniques. Biochemical imaging with positron emission tomography, (PET), and the glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose, (FDG), complements anatomic imaging with conventional radiologic methods., Methods: A new "whole-body" PET FDG technique that produces two-dimensional, nontomographic and tomographic longitudinal images of the entire body has been developed at UCLA. Sixteen patients with known pulmonary nodules who had undergone thoracic computed tomography (CT) were studied with whole-body PET FDG imaging at the UCLA Medical Center., Results: This PET FDG imaging method identified metabolically active tumor foci in all eight patients with bronchogenic carcinomas, four patients with metastatic lesions to the thorax, and two patients with Hodgkin disease. All diagnoses were confirmed histologically. Additionally, the PET FDG technique detected extrathoracic metastases in 4 of 16 patients. Thoracic CT was not diagnostic of neoplasm in two of the eight patients with bronchogenic carcinomas. In one patient with an ACTH-producing bronchial carcinoid, the lesion ultimately was detected on high-resolution CT but was not metabolically active on PET FDG imaging., Conclusions: This is the first report of whole-body PET FDG imaging in patients with thoracic lesions. PET FDG imaging accurately detected metabolically active tumor (both intrathoracic and extrathoracic) in patients with bronchogenic carcinoma, pulmonary metastatic disease, and Hodgkin lymphoma. Because lung cancer is characteristically a multisystem disease, this whole-body PET FDG technique has significant implications for treatment planning.

The results of a receiver operator characteristic (ROC) study comparing maximum likelihood estimator (MLE) reconstructions of human FDG PET brain scan data to filtered backprojection reconstructions of the same data are reported. The purpose of the study was to determine whether MLE reconstructions would result in higher detectability of small focal lesions introduced artificially into otherwise normal scan data. One physician assisted in defining the location and intensity of the lesions and five physicians read the final images. Data from 90 datasets were used for the study. Of those, 42 were left in their original "normal" condition and 48 were modified by added lesions. All datasets were reconstructed by the two methods and submitted to the five physicians for evaluation. The results show an increase in the area under the ROC curve from approximately 0.65 for filtered backprojection to approximately 0.71 for the maximum likelihood reconstructions for four of the five observers with good statistical significance.

Distant sites of metastatic fallopian tube carcinoma, including humerus, umbilicus, and groin, were clearly imaged with FDG-PET; the surgical-pathologic correlations are presented. In disorders such as ovarian or fallopian tube cancer, where a reliable means of diagnosing persistent or recurrent disease remains elusive, PET scanning offers another approach to this problem. Based on the increased rate of glucose metabolism in tumors, this modality focuses on the biochemical differences between malignant tissues and their normal counterparts in order to demonstrate positive findings on imaging. Potential uses of PET scanning in gynecologic oncology are presented.

We developed a method for evaluating tumor glycolytic rates in vivo with nude mice injected with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) and a dedicated animal positron emission tomography (PET) scanner. Animals were injected with NR-6 mouse fibroblast tumor cell lines. When tumors achieved a large enough size to be macroscopically visible, quantitative measurements of FDG uptake in vivo were obtained, using both standard nonlinear regression with the FDG tracer kinetic model to generate estimates of model parameters, including KNLR, the rate constant for net phosphorylation of FDG. Additionally, we determined the values of KPAT, the rate constant for net phosphorylation of FDG measured with a non-iterative graphical method. Estimates of K were highly correlated (r = 0.95) with both methods, and parametric images of KPAT demonstrate both the tumor location and size, but are also scaled in units of phosphorylation of FDG. The method is suitable for serial studies of tumor glucose metabolism during and after therapeutic interventions, such as chemotherapeutic trials.

The goal of this study was to identify the anatomic and physiologic factors affecting left ventricular myocardial 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) uptake and myocardial glucose utilization rates (MRGlc) in normal humans. Eighteen healthy male volunteers were studied in the fasting state (4-19 h) and 16 after oral glucose loading (100 g dextrose) with positron emission tomography (PET) and FDG. Substrate and hormone concentrations were measured in each study. The kinetics of myocardial FDG uptake were evaluated using both a three-compartment model and Patlak graphical analysis. Systolic blood pressures and rate pressure products were similar in the fasting and postglucose states. MRGlc averaged 0.24 +/- 0.17 mumol/min/g in fasting subjects and rose to 0.69 +/- 0.11 mumol/min/g after glucose loading. Phosphorylation rate constant, k3, and MRGlc were linearly related (P < 0.001). Increases in MRGlc following glucose loading were correlated with plasma glucose, insulin and free fatty acid concentrations, ratios of insulin to glucagon levels, and influx rate constants of FDG. Glucose loading improved the diagnostic image quality due to more rapid clearance of tracer from blood and higher myocardial FDG uptake. When MRGlc, glucose and insulin concentrations, and insulin to glucagon ratios exceeded 0.2 mumol/min/g, 100 mg/dl, 19 microU/ml, and 0.2 microU/pg, respectively, myocardial uptake of FDG was always adequate for diagnostic use. FDG image quality and MRGlc were similar after relatively short (6 +/- 2 h) and overnight (16 +/- 2 h) fasting. Significant (P < 0.05) regional heterogeneity of myocardial FDG uptake and MRGlc was observed in both the fasting and the postglucose studies. MRGlc and FDG uptake values in the posterolateral wall were higher than those in the anterior wall and septum. Thus, both 6-h and overnight fasts resulted in similarly low myocardial glucose utilization rates. While MRGlc and myocardial FDG uptake depended on plasma glucose, free fatty acid, and insulin concentrations, the results also suggest an additional dependency on plasma glucagon levels. Regional heterogeneities in myocardial FDG uptake and MRGlc are evident and independent of the subjects' dietary state. These regional heterogeneities need to be considered in studies of patients with cardiac disease.

The value of whole body positron emission tomography using F-18 2-deoxy-2-fluoro-d-glucose in primary work-up and follow-up was prospectively evaluated in 37 patients with primary or metastatic breast cancer. From 20 primary breast masses 15 from 16 malignant and 4 from 4 benign lesions confirmed by biopsy, were detected. In 3 out of 21 patients in correlation to morphologic imaging, respectively biopsy, no metastatic disease was not identified. Generally speaking, whole body positron emission tomography appears to be a suitable diagnostic staging tool in breast cancer.

The utility of Patlak graphical analysis was investigated for quantification of regional myocardial blood flow (MBF) and for generating parametric images of MBF with 13N-ammonia and dynamic PET imaging in dogs and humans. MBF was estimated by a two-compartment model fit of the initial 2 min of the kinetic data and by Patlak graphical analysis of the initial 2, 3, or 4 min of data. In 11 dog studies, MBF by compartmental model fitting linearly correlated with MBF by microspheres (correlation coefficient (r) = 0.99, slope = 0.92) and by Patlak graphical analysis (r = 0.99, slope = 0.90). In 10 normal human studies, MBF obtained by the Patlak graphical analysis agreed well with MBF obtained by the compartmental model fitting (r = 0.96, slope = 1.04). Good agreement of the MBF estimates was also observed in 10 coronary artery disease patient studies (r = 0.96). Patlak graphical analysis permitted generation of parametric images of MBF. The parametric images of MBF, in units of ml/min/g, are of good image quality and have relatively low noise levels. We conclude that regional MBF can be noninvasively and conveniently measured with dynamic 13N-ammonia PET using either a two-compartment model or Patlak graphical analysis. MBF parametric images generated with the Patlak graphical analysis both map the distribution and quantitate the magnitude of myocardial perfusion abnormalities.

Using our recently reported whole body PET imaging technique, we performed whole body PET studies of the skeletal system with [18F]fluoride ion in 19 patients with a range of malignant and benign skeletal conditions and in 19 normal male volunteers. The technique produces two-dimensional projection images of the entire skeletal system ("a PET bone scan"), in addition to coronal, sagittal, and axial tomographic images of the skeletal system. The tomographic images had a 13% higher lesion detection sensitivity than the projection images. Whole body PET skeletal imaging with [18F]fluoride ion is technically feasible, provides images of excellent quality, and may be coupled with more quantitatively precise kinetic PET [18F]fluoride ion studies (over limited regions of the body) when numerical estimates of skeletal [18F]fluoride ion uptake are desired. The method is potentially useful in clinical applications where the high resolution and numerical precision of PET are of particular value (e.g., in accurately defining the anatomic location and extent of lesions and in assessing changes in bone metabolism on serial studies).

The aim of this study was to define and quantitate the normal anatomy of the extracranial head and neck with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). This information was used to study 12 patients with primary squamous cell carcinomas. In all cases, the lymphoid tissue of the Waldeyer ring and the palatine and lingual tonsils could be differentiated from the airway, striated muscle, osseous structures, and salivary glands. Striated muscle had markedly less activity than lymphoid or salivary gland tissue. In the 12 patients with primary tumors, FDG PET depicted the tumor as an area of increased activity significantly higher than that of normal tissue. In one instance, FDG PET allowed detection of a tumor not seen at magnetic resonance (MR) imaging or computed tomography. Of the 34 lymph nodes positive for carcinoma, 24 were positive according to MR size criteria and 25 were detected with FDG PET. FDG PET allowed detection of three nonenlarged metastatic nodes that were negative at MR imaging.

Imaging and quantifying biochemical and physiological processes with PET clearly has major potential significance for all organ systems and many disease states. Although the full utility and potential of emerging new applications of PET in organs other than the heart and brain must be demonstrated in basic and clinical research studies, the rapidly accumulating aggregate experience in oncology in particular, and in other organ systems and disease states as well, indicates that PET is now truly becoming a modality of both clinical and investigative use for the body as a whole as well as for specific organ systems. Whole-body PET FDG imaging (Fig 9) illustrates the potential of biochemical imaging to map the distribution of cancer throughout the body. With the growing list of radiopharmaceutical and quantitative techniques applicable to cancer studies with PET, this field will continue to realize significant growth.