fluoro-D-glucose Positron Emission Tomography Research Articles

Positron Emission Tomography: An Advanced Nuclear Medicine Imaging Technique from Research to Clinical Practice

This chapter describes the use of positron emission tomography (PET) in clinical practice. PET is an advanced diagnostic imaging technique, which can not only detect and localize, but also quantify physiological and biochemical processes in the body noninvasively. The ability of PET to study various biological processes opens up the new possibilities for both fundamental research and day-to-day clinical use. PET has played an important role for both diagnostic and therapeutic purposes in patients with neurological and cardiological infections and inflammations, vasculitis, and other autoimmune diseases. Fluoro-d–glucose (FDG) PET has been used successfully as a noninvasive diagnostic test for solitary pulmonary nodules (SPN) in order to distinguish benign lesions from malignancies. It is found that a whole-body FDG PET scan is as accurate as a panel of imaging modalities currently employed in detecting disease and is significantly more accurate in detecting multifocal disease, lymph node involvement, and distant metastasis. FDG PET is also accepted as a useful and highly sensitive tool for the localization of epileptogenic zones.

Measurement of the Global Lumped Constant for 2-Deoxy-2-[ 18F]Fluoro-D-Glucose in Normal Human Brain Using [ 15O]Water and 2-Deoxy-2-[ 18F]Fluoro-D-Glucose Positron Emission Tomography Imaging : A Method with Validation Based on Multiple Methodologies

PURPOSE: This study aims to determine a lumped constant (LC) value that can be applied to the 2-deoxy-2[ 18F]fluoro-D-glucose positron emission tomography (FDG-PET) study to yield a physiological value of cerebral metabolic rate of glucose (CMR glc) in normal brain. PROCEDURES: We developed a more robust method for determining the global FDG LC. Dynamic FDG and H 2 15O PET studied were acquired in 18 normal subjects. Arterial-venous difference of blood glucose level was measured. RESULTS: A global LC of 0.65 ± 0.15 was obtained if a 3-microparameter FDG model ( k 4 *=0)was assumed. Assumption of a 4-microparameter FDG model ( k 4 *≠0) in analyzing the FDG data resulted in a higher LC value of 0.81 ± 0.18. CONCLUSION: The value of LC used for quantitating CMR glc should match the assumption inherent to the method of data analysis. The LC results in this study agree well with recent findings in the literature.

Sarcoidosis and Sarcoid-Like Reaction Following Hodgkin's Disease: Report of Two Cases

The occurrence of a sarcoidosis associated with Hodgkin's disease is an infrequent but well-described event. Moreover it has been described for many decades that some malignancies may present with simultaneous granulomatous manifestations named sarcoid-like reactions. To differentiate sarcoidosis from the sarcoid-like reactions is not an easy step in the final diagnosis. No author in the past has included the use of 2-deoxy-2[ 18F]fluoro-D-glucose positron emission tomography (FDG-PET) in order to help in this differentiation. We report two patients with Hodgkin's disease complicated with a typical form of sarcoidosis and with diffuse sarcoid-like reactions. We discuss the use of FDG-PET as a tool in the making of the final diagnosis and the difficulties associated with this technique in the interpretation of different hypermetabolic tissues.

2-Deoxy-2-[ 18F]Fluoro-D-Glucose Positron Emission Tomography Uptake in a Giant Adrenal Myelolipoma

Incidental adrenal lesions found on anatomic imaging are not uncommon. 2-Deoxy-2-[ 18F]fluoro-D-glucose positron emission tomography (FDG-PET) imaging is highly accurate in the differentiation of benign from malignant adrenal lesions, both in patients with proven malignancy and with adrenal lesions detected incidentally. A 60-year-old white female with a history of lower mid-back pain underwent computerized tomography (CT) imaging that identified a 15-cm complex mass within the left adrenal gland with soft tissue, cystic, and adipose components. FDG-PET imaging showed significant hypermetabolic activity within portions of the mass with central photopenia suggesting a malignant lesion with central necrosis. Surgical excision and pathological examination, however, revealed a benign adrenal myelolipoma with extensive adenomatous and hematopoietic elements. Prior reports of adrenal myelolipoma evaluated with FDG-PET imaging have described no significant FDG uptake within these benign tumors. This case is an unusual example of histologically proven benign adrenal myelolipoma that was hypermetabolic on FDG-PET imaging. Correlation of pathologic and imaging findings demonstrated that the hypodense regions on CT were hypometabolic on FDG-PET and corresponded to cystic necrosis and adipose elements, whereas the adenomatous and hematopoietic elements were hypermetabolic.(Mol Imag Biol 2002;4:355–358)

Cerebral Lesions Incidentally Detected on 2-Deoxy-2-[ 18F]Fluoro-D-Glucose Positron Emission Tomography Images of Patients Evaluated for Body Malignancies

Objectives: The purpose of this work was done to evaluate the value of including the brain in the field of view of a whole-body 2-deoxy-2-[ 18F] fluoro-D-glucose positron emission tomography (FDG-PET) study of patients referred for the evaluation of body malignancies. Methods: A total of 1026 consecutive patients were included in this work. The primary diagnoses were the following: lung (n = 253), colorectal (n = 148), head and neck (n = 61), lymphoma (n = 249), melanoma (n = 84), and others (n = 231). Whole-body FDG images including the brain were acquired with a dedicated PET tomograph (GE advance, General Electronic Medical Systems, Milwaukee, WI) one hour after the intravenous administration of 10 mCi of FDG. Two experienced nuclear medicine physicians interpreted the images. Positive findings in the brain or the skull were correlated with other imaging studies and clinical follow-up. Results: Abnormal findings were detected in 3.9% (40/1026) of the patients. Among the 40 abnormal focal lesions, 29 patients had a known history of cerebral disease, cerebrovascular or metastatic disease in most patients. Of the 11 patients without a prior history of cerebral disease, four patients had increased focal FDG uptake suggestive of metastases. Among these, two were proven clinically, one was proven to be a skull base metastasis on MRI, and the other had negative clinical follow-up, but only of two months duration. The other seven patients had a decreased focal FDG uptake most consistent with infarct, one was proven clinically, and the other six had a negative clinical follow-up (mean of 6.3 months, range 1–10), but had multiple risk factors for cerebrovascular disease. Conclusions: We conclude that FDG-PET screening for cerebral lesions in patients with body malignancy has little clinical impact. Unsuspected cerebral or skull metastases were detected in 0.4% (4/1026) of the patients. (Mol Imag Biol 2002;4:359–362)

2-Deoxy-2-[ 18F]Fluoro-D-Glucose Positron Emission Tomography Monitoring Disease Progress in a Patient with Islet Carcinoma of the Pancreas

A woman with islet cell carcinoma of the pancreas proven by biopsy at an exploratory laparotomy underwent six cycles of chemotherapy with paclitaxel and carboplatin. After the chemotherapy to monitor her primary tumor and hepatic metastases, she had three consecutive 2-deoxy-2-[ 18F]fluoro-D-glucose positron emission tomography (FDG-PET) determinations that correlated with an In-111 octreotide single photon emission computer tomography. FDG-PET might have utility in monitoring islet cell carcinoma of the pancreas in evaluating metabolic changes following chemotherapy.

Standardized Uptake Values in 2-Deoxy-2-[ 18F]Fluoro-D-Glucose with Positron Emission Tomography : Clinical Significance of Iterative Reconstruction and Segmented Attenuation Compared with Conventional Filtered Back Projection and Measured Attenuation Correction

Purpose: To evaluate the clinical significance of differences in 2-deoxy-2-[ 18F]fluoro-D-glucose positron emission tomography (FDG-PET) lymph node standardized uptake values (SUV) in human immunodeficiency virus (HIV) infection using iterative reconstruction with segmented attenuation correction (IR SAC) compared to filtered back-projection with measured attenuation correction (FBP MAC). Procedures: Seven patients with HIV infection and multiple focal lymph node abnormalities were investigated with whole-body FDG-PET. Mean and maximum SUVs from lymph node regions of interest (n = 961) were compared for quantitative differences between reconstruction techniques. Results: IR MAC resulted in significantly lower mean SUV [0.06; 95% (confidence interval (CI)) = 0.04–0.07] and maximum SUV (0.82; 95% CI = 0.77–0.88) values compared to FBP MAC. With IR, segmentation of attenuation correction (AC) resulted in significantly higher mean SUV (0.12; 95% CI = 0.11–0.13) and maximum SUV (0.21; 95% CI = 0.18–0.23) values compared to IR MAC. The overall effect of both IR and SAC was a slight but significant increase in mean SUV (0.06; 95% CI = 0.06–0.08; bias = 2.1%) and a significant decrease in maximum SUV (0.62; 95% CI = 0.56–0.67) compared to FBP MAC. Conclusions: With our reconstruction parameters, significant differences in mean and maximum SUV values were observed. The magnitude of the mean SUV difference, however, was small. IR SAC is a promising method to accurately quantify standardized uptake values for clinical use.

2-Deoxy-2-[ 18F]Fluoro-D-Glucose Positron Emission Tomography in Target Volume Definition for Radiotherapy of Patients with Non-Small-Cell Lung Cancer

Purpose: To discuss the potential contribution of 2-deoxy-2-[ 18F]fluoro-D-glucose positron emission tomography (FDG-PET) in radiotherapy planning for non-small-cell lung cancer (NSCLC) considering new concepts on target volume definition. Procedures: Recent investigations on the topic are reviewed with regard to current concepts of target volume definition for NSCLC. Results: As intrathoracic recurrence is the leading cause of death after primary radiotherapy of NSCLC, there is a need for improving local control by escalating treatment intensity to gross disease. The value of elective nodal irradiation (ENI), resembling prophylactic irradiation of macroscopically unaffected parts of the mediastinum, is being considered. Conclusion: As FDG-PET has been shown to enhance the diagnostic accuracy of computed tomography (CT), and to have a potentially high impact on the identification of malignant tissue, it should be implicated in prospective clinical trials on dose escalation and three-dimensional conformal radiotherapy, especially in those including a reduction of target volumes. (Mol Imag Biol 2002;4:257–263)

The Receiver Operating Characteristic Curve for the Standard Uptake Value in a Group of Patients with Bone Marrow Metastasis

Purpose: The aim of this work was to determine the standard uptake value (SUV) threshold for differentiating malignant from benign bone lesions. Material and methods: Ninety-nine bone sites in 33 patients who had undergone a 2-deoxy-2-[ 18F]fluoro-D-glucose-positron emission tomography (FDG-PET) study for cancer evaluation were studied. In addition to FDG-PET, a bone scan and at least two of the following determinations: magnetic resonance imaging (MRI), computed tomography (CT), and x-ray were conducted in each patient. The bone lesions were considered positive for malignancy if confirmed by clinical follow-up or a high degree of suspicion based on the positive results of at least three (which must include bone scan) out of four other imaging modalities. By these criteria, 39 lesions were considered positive and 60 were considered negative. The SUV values were classified as positive or negative using 61 different values of threshold (range from 1.0 to 7.0). These results were compared with the positive criteria above and reclassified as true positive, true negative, false positive, and false negative. The true-positive fraction and false-positive fraction were calculated for each threshold value. The receiver operating characteristic (ROC) curve was drawn and the best value was determined by visual analysis . Results: The SUV threshold was considered 2.5. Twenty-nine out of 39 bone lesions classified as positive showed a SUV > 2.5. Of the 10 false-negative lesions, seven showed a SUV between 1.1 and 2.0, and three were not detected. Fifty-six out of 60 lesions classified as negative showed a SUV < 2.5. Four lesions were false positive: one was a rib fracture and three were severe degenerative changes in the lumbar spine. Using an SUV threshold of 2.5, the sensitivity was 74.3% and the specificity was 93.3%. Conclusion: In our patient population, the optimal SUV to classify a bone lesion as malignant or benign is 2.5. (Mol Imag Biol 2002;4:157–160)

Prognostic Value of 2-Deoxy-2-[F-18]Fluoro-D-Glucose Positron Emission Tomography Imaging for Patients with Prostate Cancer

Purpose: The purpose of this study was to investigate the prognostic value of measuring glucose metabolism of primary prostate cancer lesions, using 2-Deoxy-2-[F-18]Fluoro-D-Glucose positron emission tomography (FDG-PET). Procedures: Forty-two patients with prostate cancer were investigated with FDG-PET, and standardized uptake value (SUV) of the prostate was calculated. After PET study, radical prostatectomy was performed in 17 patients (RPT group), and endocrine therapy in 25 patients (ET group). Relapse-free survival curves were created by the Kaplan-Meier method. Results: In the RPT group, the patients with high SUV had a poorer prognosis compared to those with low SUV ( P = 0.033). In the ET group, the patients with high SUV were likely to have a poorer prognosis with low significance at a level of P = 0.087. Conclusions: FDG-PET appeared to have a defined prognostic value for patients with prostate cancer undergoing radical prostatectomy, and more patients need to be studied for patients undergoing endocrine therapy. (Mol Imag Biol 2002;4:99–104)

Pulmonary abnormalities and PET data analysis: a retrospective study.

To assess methods of standard uptake ratio (SUR) calculation with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron emission tomography (PET) in indeterminate focal pulmonary abnormalities. One hundred ninety-seven adult patients with indeterminate pulmonary abnormalities had complete FDG PET data, consistent methods of data acquisition, and definitive diagnosis with tissue biopsy or negative 2-year follow-up findings. PET studies were evaluated by using SURs calculated with the average or maximum region-of-interest pixel value in the numerator and with weight, lean body mass, or body surface area in the denominator. One hundred twenty malignant lesions and 77 benign processes were identified. Receiver operating characteristic (ROC) curve areas were statistically significantly larger with the average rather than the maximum pixel value in the calculation of the SUR for any of the three denominators (P < or = .05). SURs calculated with weight versus lean body mass versus body surface area in the denominator showed no statistically significant difference in ROC curve areas. SURs determined by using average pixel values provide statistically significant improvement in ROC curve areas over those determined by using maximum pixel values. Weight, lean body mass, and body surface area in the denominator of the SUR calculation provide equivalent ROC curve areas and are therefore equivalent in accuracy in this population.

Recurrence of head and neck cancer after surgery or irradiation: prospective comparison of 2-deoxy-2-[F-18]fluoro-D-glucose PET and MR imaging diagnoses.

To evaluate the diagnostic accuracy of positron emission tomography (PET) with administration of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) relative to that of magnetic resonance (MR) imaging and/or computed tomography (CT) in recurrent head and neck cancers. Twelve adult patients (mean age, 63 years) with previously treated head and neck cancers and clinical suspicion of recurrence underwent FDG PET and MR imaging and/or CT. All images were blindly and independently interpreted without histopathologic findings (obtained within 1 week of imaging). The level of confidence in image interpretation was graded by using a five-point rating system (0 = definitely no recurrence to 4 = definite recurrence). Recurrence was confirmed in eight patients. With a rating of 4 as a positive finding, FDG PET yielded a sensitivity and specificity of 88% (seven of eight) and 100% (four of four), respectively; MR imaging and/or CT, 25% (two of eight) and 75% (three of four), respectively. Receiver-operating characteristic analysis showed significantly better diagnostic accuracy with FDG PET than with MR imaging and/or CT (area under curve = 0.96 vs 0.55, P < .03). These data indicate that PET metabolic imaging, as compared with anatomic methods, has improved diagnostic accuracy for recurrent head and neck cancer.

Metastatic prostate cancer: initial findings of PET with 2-deoxy-2-[F-18]fluoro-D-glucose.

To evaluate the accuracy of positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) in the detection of osseous and soft-tissue metastases of prostate cancer. Thirty-four patients (mean age, 71 years) with biopsy-proved prostate cancer and known or suspected metastatic disease were examined. Blinded interpretation of the PET images was compared with bone scan, CT, and clinical follow-up findings. In 202 untreated osseous metastases in 22 patients, the sensitivity of FDG PET was 65% (131 of 202 metastases), with a positive predictive value of 98% (131 of 133 positive findings). The estimated standardized uptake value in metastases was 2.1-5.7. Soft-tissue metastases to the lymph nodes or liver were identified, but evaluation of pelvic lymph node metastases was severely limited because of bladder tracer activity. FDG PET can help identify osseous and soft-tissue metastases of prostate cancer with a high positive predictive value but is less sensitive than bone scintigraphy in the identification of osseous metastases.

Calendar

2-Deoxy-2-[18F]fluoro-D-Glucose positron emission tomography (FDG-PET) stages patients with Hodgkin's disease (HD) and Non-Hodgkin's lymphoma (NHL) with higher accuracy than computed tomography (CT). We sought to determine whether integrated (hardware) fused PET/CT imaging results in further improvements in staging accuracy.Seventy-three patients (age 51 ± 17 years, 37 female, 36 male) with HD (n = 20) or NHL (n = 53) undergoing staging were studied with an integrated PET/CT system. Image findings were verified by clinical follow up, additional imaging and when available, histology.Thirty-four of 73 patients (46.5%) had evidence of disease and 39 were disease free as confirmed by clinical evaluation and follow-up for 41 ± 22 weeks (n = 73), including biopsy (n = 26), and other imaging modalities (n = 52) when available. A discordant image interpretation between PET and PET/CT occurred in seven patients (10%). PET/CT correctly upstaged two and downstaged five patients. Overall staging was accurate in 93% with PET/CT and 84% with PET (P = 0.03).Lymphoma is staged with higher accuracy using PET/CT than PET alone.

Imaging of Renal Cancer Using Positron Emission Tomography with 2-Deoxy-2-(18F)-Fluoro-D-Glucose: Pilot Animal and Human Studies

The feasibility of imaging renal cancers with 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) and whole-body positron emission tomographic scanning was assessed in nude mice with human renal adenocarcinoma xenografts and then in 5 patients with primary renal cancer (4 adenocarcinomas and 1 transitional cell carcinoma). In nude mouse biodistribution studies tumor FDG uptake was maximal at 0.33 to 2 hours but tumor-to-blood ratios increased continuously to 7.8/1. by 4 hours after intravenous FDG injection. In all 5 patients primary and metastatic tumors were imaged within 1 hour by FDG positron emission tomography following intravenous injection of the FDG. By contrast, an hepatic hemangioma did not accumulate FDG. In summary, FDG metabolic and anatomical imaging of primary and metastatic renal cancer is feasible and in these pilot studies appears to be a promising imaging methodology that may be further enhanced by delayed imaging times. Additional study in a larger number of patients is essential to define better the accuracy and potential clinical use of this method.