Performance characteristics of amyloid PET with florbetapir F 18 in patients with alzheimer's disease and cognitively normal subjects.

UNLABELLED: The objectives of this study were to examine the effective dose range and the test-retest reliability of florbetapir F 18 using, first, visual assessment by independent raters masked to clinical information and, second, semiautomated quantitative measures of cortical target area to cerebellum standardized uptake value ratios (SUVr) as primary outcome measures. Visual ratings of PET image quality and tracer retention or ß-amyloid (Aß) binding expressed as SUVrs were compared after intravenous administration of either 111 MBq (3 mCi) or 370 MBq (10 mCi) of florbetapir F 18 in patients with Alzheimer's disease (AD) (n = 9) and younger healthy controls (YHCs) (n = 11). In a separate set of subjects (AD, n = 10; YHCs, n = 10), test-retest reliability was evaluated by comparing intrasubject visual read ratings and SUVrs for 2 PET images acquired within 4 wk of each other. RESULTS: There were no meaningful differences between the 111-MBq (3-mCi) and 370-MBq (10-mCi) dose in the visual rating or SUVr. The difference in the visual quality across 111 and 370 MBq showed a trend toward lower image quality, but no statistical significance was achieved (t test; t(1) = -1.617, P = 0.12) in this relatively small sample of subjects. At both dose levels, visual ratings of amyloid burden identified 100% of AD subjects as Aß-positive and 100% of YHCs as Aß-negative. Mean intrasubject test-retest variability for cortical average SUVrs with the cerebellum as a reference over the 50- to 70-min period was 2.4% ± 1.41% for AD subjects and 1.5% ± 0.84% for controls. The overall SUVr test-retest correlation coefficient was 0.99. The overall κ-statistic for test-retest agreement for Aß classification of the masked reads was 0.89 (95% confidence interval, 0.69-1.0). CONCLUSION: Florbetapir F 18 appears to have a wide effective dose range and a high test-retest reliability for both quantitative (SUVr) values and visual assessment of the ligand. These imaging performance properties provide important technical information on the use of florbetapir F 18 and PET to detect cerebral amyloid aggregates.

Variable cardiac 18FDG patterns seen in oncologic positron emission tomography computed tomography: importance for differentiating normal physiology from cardiac and paracardiac disease.

PURPOSE: Cardiac fluorine-18-fluorodeoxyglucose (FDG) uptake is known to be variable in fasting oncologic positron emission tomography computed tomography studies. Increased posterolateral and basal FDG activity have been reported with the basal pattern ascribed to radiation injury. The purpose of this study was to investigate the spectrum of normal cardiac FDG findings seen in oncologic patients. MATERIALS AND METHODS: Men <35 years of age and women <45 years of age seen over a 3-year period were included. A visual assessment of FDG cardiac activity was performed using a 12-segment model of the heart by 2 observers. Focal papillary muscle activity was not included in the analysis. RESULTS: Of 65 patients who met the entry criteria, increased FDG activity was observed in the base of the heart in 37 (57%) patients. This was most common in the lateral-basal wall in 35 (54%) patients, followed by posterior-basal wall in 21 (32%) patients, anterior-basal wall in 10 (15%) patients, and basal-septum in 10 (15%) patients. Suppression of total cardiac activity was present in only 6 (9%) patients in spite of adequate fasting. Diffuse cardiac activity was seen in 9 (14%) patients. The previously reported increased posterolateral pattern was present in only 9 (14%) patients. CONCLUSION: This study confirms variable fasting FDG cardiac activity with a predominant basal pattern not associated with radiation injury. Knowledge of these patterns is important for recognition of possible underlying cardiac ischemia, tumor, or other inflammatory conditions encountered during interpretation of oncologic positron emission tomography computed tomography studies.

How to differentiate benign versus malignant cardiac and paracardiac 18F FDG uptake at oncologic PET/CT.

Patients undergoing 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) whole-body oncologic positron emission tomography (PET)/computed tomography (CT) are studied while fasting. Cardiac FDG uptake in fasted patients has been widely reported as variable. It is important to understand the normal patterns of cardiac FDG activity that can be seen in oncologic FDG PET/CT studies. These include focal and regional patterns of increased FDG myocardial activity. Focal activity can be observed in papillary muscles, the atria, the base, and the distal anteroapical region of the left ventricle. Regional increased cardiac FDG activity may be diffuse or localized in the posterolateral wall or the base of the left ventricle. Abnormal patterns of cardiac FDG activity not related to malignancy include those associated with lipomatous hypertrophy of the interatrial septum, epicardial and pericardial fat, increased atrial activity associated with atrial fibrillation or a prominent crista terminalis, cardiac sarcoidosis, endocarditis, myocarditis, and pericarditis. Knowledge of these patterns of cardiac FDG activity is important to be able to recognize malignant disease involving the paracardiac spaces, myocardium, and pericardium. With a better understanding of the range of normal and abnormal patterns of cardiac FDG activity, important benign and malignant diseases involving the heart and pericardium can be recognized and diagnosed.

F-18 fluorodeoxyglucose-positron emission tomography imaging for primary breast cancer and loco-regional staging.

Breast cancer is the most common female malignancy in Western countries. The limitations of mammography, ultrasound and MRI do not allow reliable identification of primary breast cancer at early stages. Functional breast imaging with positron emission tomography (PET) and F-18 fluorodeoxyglucose (FDG) enables the visualization of increased glucose metabolism of breast cancer. However, despite the successful identification of primary breast cancer, FDG-PET provides a low sensitivity to detect small tumors. Therefore, FDG-PET does not allow screening of asymptomatic women and cannot be used to exclude breast cancer in patients with suspicious breast masses or abnormal mammography. FDG-PET is a powerful tool for staging of breast cancer patients, but does not detect micrometastases and small tumor infiltrated lymph nodes. Nevertheless, in patients with locally advanced breast cancer, PET accurately determines the extent of disease, particularly the loco-regional lymph node status. Advances in technology, for example the development of dedicated breast imaging devices such as positron emission mammography, hold promise to improve the detection of primary tumors in the future.

High-resolution fluorodeoxyglucose positron emission tomography with compression ("positron emission mammography") is highly accurate in depicting primary breast cancer.

We sought to prospectively assess the diagnostic performance of a high-resolution positron emission tomography (PET) scanner using mild breast compression (positron emission mammography [PEM]). Data were collected on concomitant medical conditions to assess potential confounding factors. At four centers, 94 consecutive women with known breast cancer or suspicious breast lesions received 18F-fluorodeoxyglucose (FDG) intravenously, followed by PEM scans. Readers were provided clinical histories and x-ray mammograms (when available). After excluding inevaluable cases and two cases of lymphoma, PEM readings were correlated with histopathology for 92 lesions in 77 women: 77 index lesions (42 malignant), 3 ipsilateral lesions (3 malignant), and 12 contralateral lesions (3 malignant). Of 48 cancers, 16 (33%) were clinically evident; 11 (23%) were ductal carcinoma in situ (DCIS), and 37 (77%) were invasive (30 ductal, 4 lobular, and 3 mixed; median size 21 mm). PEM depicted 10 of 11 (91%) DCIS and 33 of 37 (89%) invasive cancers. PEM was positive in 1 of 2 T1a tumors, 4 of 6 T1b tumors, 7 of 7 T1c tumors, and 4 of 4 cases where tumor size was not available (e.g., no surgical follow-up). PEM sensitivity for detecting cancer was 90%, specificity 86%, positive predictive value (PPV) 88%, negative predictive value (NPV) 88%, accuracy 88%, and area under the receiver-operating characteristic curve (Az) 0.918. In three patients, cancer foci were identified only on PEM, significantly changing patient management. Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging, PEM sensitivity was 91%, specificity 93%, PPV 95%, NPV 88%, accuracy 92%, and Az 0.949 when interpreted with mammographic and clinical findings. FDG PEM has high diagnostic accuracy for breast lesions, including DCIS.

F-18 Fluorodeoxyglucose-Positron Emission Tomography Imaging for Primary Breast Cancer and Loco-Regional Staging.

Breast cancer is the most common female malignancy in Western countries. The limitations of mammography, ultrasound and MRI do not allow reliable identification of primary breast cancer at early stages. Functional breast imaging with positron emission tomography (PET) and F-18 fluorodeoxyglucose (FDG) enables the visualization of increased glucose metabolism of breast cancer. However, despite the successful identification of primary breast cancer, FDG-PET provides a low sensitivity to detect small tumors. Therefore, FDG-PET does not allow screening of asymptomatic women and cannot be used to exclude breast cancer in patients with suspicious breast masses or abnormal mammography. FDG-PET is a powerful tool for staging of breast cancer patients, but does not detect micrometastases and small tumor infiltrated lymph nodes. Nevertheless, in patients with locally advanced breast cancer, PET accurately determines the extent of disease, particularly the loco-regional lymph node status. Advances in technology, for example the development of dedicated breast imaging devices such as positron emission mammography, hold promise to improve the detection of primary tumors in the future.

Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer.

BACKGROUND: High-resolution positron-emission mammography (PEM) is a new device, which allows the imaging of breast tissue. A prospective study was performed to assess the accuracy of PEM in newly diagnosed breast cancer patients. METHODS: In a prospective multicenter study, 44 women with confirmed breast cancers were imaged with a high-resolution PEM scanner (Naviscan PET Systems, Rockville, MD) with 18F-fluorodeoxyglucose. The images were blindly evaluated and were compared with final pathology. RESULTS: The majority of the index lesions were seen on PEM (89%, 39/44). PEM detected 4 of 5 incidental breast cancers, 3 of which were not seen by any other imaging modalities. Of 19 patients undergoing breast-conserving surgery, PEM correctly predicted 6 of 8 (75%) patients with positive margins and 100% (11/11) with negative margins. CONCLUSION: The current PEM device shows promise in detecting breast malignancies and may assist in the planning of adequate partial mastectomy procedures to better ensure negative margins.

Quantitative immuno-positron emission tomography imaging of HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody.

Positron emission tomography (PET) provides an effective means of both diagnosing/staging several types of cancer and evaluating efficacy of treatment. To date, the only U.S. Food and Drug Administration-approved radiotracer for oncologic PET is (18)F-fluoro-deoxyglucose, which measures glucose accumulation as a surrogate for malignant activity. Engineered antibody fragments have been developed with the appropriate targeting specificity and systemic elimination properties predicted to allow for effective imaging of cancer based on expression of tumor associated antigens. We evaluated a small engineered antibody fragment specific for the HER2 receptor tyrosine kinase (C6.5 diabody) for its ability to function as a PET radiotracer when labeled with iodine-124. Our studies revealed HER2-dependent imaging of mouse tumor xenografts with a time-dependent increase in tumor-to-background signal over the course of the experiments. Radioiodination via an indirect method attenuated uptake of radioiodine in tissues that express the Na/I symporter without affecting the ability to image the tumor xenografts. In addition, we validated a method for using a clinical PET/computed tomography scanner to quantify tumor uptake in small-animal model systems; quantitation of the tumor targeting by PET correlated with traditional necropsy-based analysis at all time points analyzed. Thus, diabodies may represent an effective molecular structure for development of novel PET radiotracers.

Positron emission mammography: high-resolution biochemical breast imaging.

Positron emission mammography (PEM) provides images of biochemical activity in the breast with spatial resolution matching individual ducts (1.5 mm full-width at half-maximum). This spatial resolution, supported by count efficiency that results in high signal-to-noise ratio, allows confident visualization of intraductal as well as invasive breast cancers. Clinical trials with a full-breast PEM device have shown high clinical accuracy in characterizing lesions identified as suspicious on the basis of conventional imaging or physical examination (sensitivity 93%, specificity 83%, area under the ROC curve of 0.93), with high sensitivity preserved (91%) for intraductal cancers. Increased sensitivity did not come at a cost of reduced specificity. Considering that intraductal cancer represents more than 30% of reported cancers, and is the form of cancer with the highest probability of achieving surgical cure, it is likely that the use of PEM will complement anatomic imaging modalities in the areas of surgical planning, high-risk monitoring, and minimally invasive therapy. The quantitative nature of PET promises to assist researchers interested studying the response of putative cancer precursors (e.g., atypical ductal hyperplasia) to candidate prevention agents.

Quantitation of small-animal (124)I activity distributions using a clinical PET/CT scanner.

UNLABELLED: Time-dependent PET imaging can be an important tool in the assessment of radiotracer performance in murine models. We have performed a quantitative analysis of PET images of (124)I, acquired on a clinical PET system using a small-animal phantom. We then compared the recovered activity concentrations with the known activity concentration in the phantom spheres. The recovery coefficients found from the phantom data were applied to in vivo (124)I anti-HER2/neu C6.5 diabody PET data and compared with necropsy biodistribution data from the same tumor-bearing immunodeficient mouse. METHODS: The small-animal phantom consisted of a 4 x 8 cm water-filled acrylic cylinder with hollow spheres filled with water ranging in volume from 0.0625 to 1.0 mL and activity concentration of 27 +/- 2 kBq/mL. The background activity concentrations varied from 0 to 0.05 to 0.10 of the spheres. Data were acquired at 0, 5, and 10 cm from the scanner longitudinal axis. Recovery coefficients were theoretically calculated for spheres of different volume, background-to-target concentrations, and distance from the scanner's longitudinal axis. The theoretic recovery coefficients were applied to the maximum sphere activity concentration measured from the PET images, thus obtaining a recovered activity concentration to be compared with the known activity concentration of the spheres. RESULTS: The mean recovered activity concentration for the phantom spheres was 25 +/- 2 kBq/mL. The (124)I diabody PET image of a mouse with a tumor xenograft was then analyzed using the techniques described. The tumor percentage injected dose per gram estimated from the murine PET image (4.8 +/- 0.4) compared well with those obtained from necropsy studies (5.1). CONCLUSION: This study indicates the feasibility of performing quantitative imaging on murine (124)I antibody fragment PET images using a large-bore clinical scanner, which enables high-throughput studies to evaluate the performance of PET tracers in a timely and cost-effective manner by imaging multiple animals simultaneously. Tracers deemed promising by this screening method can then be further evaluated using traditional necropsy studies. Our group is currently conducting time-dependent (124)I diabody PET and necropsy comparative studies with larger numbers of mice.

Positron emission tomography of soft tissue sarcomas.

The purpose of this review is to underscore the value of positron emission tomography (PET) in the management of patients with soft tissue sarcomas. Although the most essential step in the diagnostic evaluation of soft tissue sarcomas is tumor biopsy, functional imaging techniques is growing and becoming more popular than before. PET scan traces molecular and cellular activities of normal and tumor cells through the use of radiotracers that engage in cell metabolism. The most important and widely used tracer is fluorodeoxyglucose (18FDG). PET scan usefulness is not limited to its ability to differentiate benign from malignant lesions. The scan can detect intralesional morphologic variation which is especially true in soft tissue sarcomas, it can predict tumor grade, and it is of value in staging, restaging and prognosis. As for the time, PET is not meant to replace tissue biopsy but rather complement the biopsy to better understand the biological behavior of soft tissue sarcomas.

Method for combined FDG-PET and radiographic imaging of primary breast cancers.

The purpose of the study was to demonstrate the feasibility of a hybrid functional/anatomic breast imaging platform with biopsy capability for facilitating lesion detection and diagnosis. This platform consists of an investigative dedicated positron emission mammography (PEM) device mounted on a stereotactic X-ray mammography system, permitting sequential acquisition of mammographic and emission images during a single breast compression. There is automatic coregistration of images from both modalities, and these results can be successfully correlated with histopathologic findings. The potential utility of functional images correlated to anatomic images would include noninvasively detecting clinically and radiographically occult cancers, assessing response to therapy, discriminating between benign and malignant breast masses, and ultimately reducing the number of invasive and costly surgical interventions. A spot-digital mammogram and subsequent PEM image, collected over a 4-minute period, were obtained in a single patient with the breast in compression after intravenous injection of (F-18)-2-deoxy-2-fluoro-D-glucose (FDG) at the time of stereotactic biopsy. The authors conclude that FDG-based lesion localization information may be combined with the lesion X-ray attenuation characteristics using this common imaging platform.

Radiographic assessment of airway tumors.

The initial imaging evaluation of a patient with a suspected tracheal abnormality is the chest radiograph, which is poor for detection of central airway lesions. Prior to the development of CT, planar tomography was performed to better evaluate the deep layers of the chest. Tomography is rarely performed today for chest imaging. There have been major advances in chest radiography techniques secondary to improvements in electronics and computer technology that might ultimately improve plain film assessment of the central airways.

Positron emission mammography: initial clinical results.

BACKGROUND: Evaluation of high-risk mammograms represents an enormous clinical challenge. Functional breast imaging coupled with mammography (positron emission mammography [PEM]) could improve imaging of such lesions. A prospective study was performed using PEM in women scheduled for stereotactic breast biopsy. METHODS: Patients were recruited from the surgical clinic. Patients were injected with 10 mCi of 2-[18F] fluorodeoxyglucose. One hour later, patients were positioned on the stereotactic biopsy table, imaged with a PEM scanner, and a stereotactic biopsy was performed. Imaging was reviewed and compared with pathologic results. RESULTS: There were 18 lesions in 16 patients. PEM images were analyzed by drawing a region of interest at the biopsy site and comparing the count density in the region of interest with the background. A lesion-to-background ratio >2.5 appeared to be a robust indicator of malignancy and yielded a sensitivity of 86%, specificity of 91%, and overall diagnostic accuracy of 89%. No adverse events were associated with the PEM imaging. CONCLUSIONS: The data show that PEM is safe, feasible, and has an encouraging accuracy rate in this initial experience. Lesion-to-background ratios >2.5 were found to be a useful threshold value for identifying positive (malignant) results. This study supports the further development of PEM.

Whole body FDG-PET for the evaluation and staging of small cell lung cancer: a preliminary study.

[F18]-2-deoxy-2fluoro-D-glucose positron emission tomography (FDG-PET) is increasingly used in the diagnosis and staging of lung cancer. Despite its positive performance characteristics in non-small cell lung cancer (NSCLC), the role of FDG-PET in the staging of small cell lung cancer (SCLC) remains to be determined. We designed a prospective study to address this question. Eighteen patients with SCLC were enrolled prospectively to undergo total body FDG-PET in addition to conventional staging procedures (chest computed tomography (CT), abdominal CT, cranial CT or magnetic resonance imaging (MRI), and bone scan/bone marrow biopsy). The agreement between FDG-PET and conventional staging modalities in identifying the presence or absence of metastatic disease was compared using the Veterans Administration (VA) cooperative staging system for staging. Overall staging by FDG-PET agreed with conventional staging exams in 15/18 (83%) patients (kappa=0.67), which included eight extensive and seven limited cases. FDG-PET showed more extensive disease in two of the three patients for which FDG-PET and conventional staging disagreed. These data suggest that total body FDG-PET may be useful in the staging, treatment planning, and prognostication of SCLC. Whether FDG-PET will replace other more established staging modalities remains to be determined by larger prospective randomized controlled studies.

Rounded Atelectasis. Evaluation With (18)PET Scan.

Rounded atelectasis is a well recognized, benign cause of a pulmonary mass. While its radiographic features have been well characterized in the radiologic literature, they are not pathognomonic and patients are commonly biopsied. Positron emission tomography (PET) has become a powerful tool to distinguish between benign and malignant disease in the thorax. We present the CT and PET imaging features of three cases of biopsy proven rounded atelectasis.