Detection of bone metastases in cancer patients by 18F-fluoride and 18F-fluorodeoxyglucose positron emission tomography.

The use of positron emission tomography (PET) in clinical oncology continues to increase and although there is now a large literature on the use of PET with various tracers in a wide variety of cancers, there has previously been relatively little use specifically in the evaluation of skeletal metastases. However, a number of reports on PET in this area of oncology are now becoming available. The potential advantages of PET over conventional nuclear medicine techniques, including improved spatial resolution, absolute quantitation and the acquisition of tomographic studies as a routine, are also of potential benefit in this area. The bone agent, 18F-fluoride and the tumour agent 18F-fluorodeoxyglucose, have been used to evaluate both benign and malignant skeletal disorders qualitatively and quantitatively and the current knowledge with respect to the skeleton in cancer patients is summarised in this article.     

Skeletal PET with 18F-fluoride: applying new technology to an old tracer.

Although (18)F-labeled NaF was the first widely used agent for skeletal scintigraphy, it quickly fell into disuse after the introduction of (99m)Tc-labeled bone-imaging agents. Recent comparative studies have demonstrated that (18)F-fluoride PET is more accurate than (99m)Tc-diphosphonate SPECT for identifying both malignant and benign lesions of the skeleton. Combining (18)F-fluoride PET with other imaging, such as CT, can improve the specificity and overall accuracy of skeletal (18)F-fluoride PET and probably will become the routine clinical practice for (18)F-fluoride PET. Although (18)F-labeled NaF and (99m)Tc-diphosphonate have a similar patient dosimetry, (18)F-fluoride PET offers shorter study times (typically less than 1 h), resulting in a more efficient workflow, improved patient convenience, and faster turnarounds of reports to the referring physicians. With the widespread availability of PET scanners and the improved logistics for the delivery of (18)F radiopharmaceuticals, prior limitations to the routine use of (18)F-fluoride bone imaging have largely been overcome. The favorable imaging performance and the clinical utility of (18)F-fluoride PET, compared with (99m)Tc-diphosphonate scintigraphy, support the reconsideration of (18)F-fluoride as a routine bone-imaging agent.     

Skeletal scintigraphy with 18F-NaF PET for the evaluation of bone pain in children

OBJECTIVE: Although not commonly used in current clinical practice, the PET agent (18)F-NaF provides an excellent alternative to the standard tracers used for radionuclide bone scintigraphy. This article illustrates the use and appearance of (18)F-NaF PET and shows examples of its utility in the assessment of bone pain in children. CONCLUSION: Skeletal imaging with (18)F-NaF harnesses both the superior imaging characteristics of PET and the improved biodistribution of the fluoride tracer in comparison with standard nuclear techniques, resulting in excellent-quality images that can effectively be used to investigate the cause of bone pain in children.     

The role of fluorodeoxyglucose, 18F-dihydroxyphenylalanine, 18F-choline, and 18F-fluoride in bone imaging with emphasis on prostate and breast

Diagnostic imaging has played a major role in the evaluation of patients with bone metastases. The imaging modalities have included bone scintigraphy, computed tomography, magnetic resonance imaging, and most recently PET/CT, which can be performed with different tracers, including fluorodeoxyglucose (FDG), 18F-fluoride, 18F-choline (FCH), and 18F-DOPA (dihydroxyphenylalanine). For most tumors the sensitivity of FDG in detecting bone metastases is similar to bone scintigraphy; additionally it can be used to monitor the response to chemotherapy and hormonal therapy. 18F-Fluoride may provide a more sensitive "conventional" bone scan and is superior for FDG nonavid tumors, but, nevertheless, FDG in "early disease" often has clear advantages over 18F-fluoride. Although more data need to be obtained, it appears that FCH is highly efficient in preoperative management regarding N and M staging of prostate cancer once metastatic disease is strongly suspected or documented. For neuroendocrine tumors and in particular in medullary thyroid cancer, DOPA is similar to 18F-fluoride in providing high quality information regarding the skeleton. Nevertheless, prospective studies with large patient groups will be essential to define the exact diagnostic role of FCH and DOPA PET in different clinical settings.     

PET评价骨转移瘤

肿瘤骨转移会产生顽固性骨痛和脊髓受压等严重并发症,并对分期、治疗和判断预后产生深远的影响,因而探测骨转移是制定治疗计划的重要部分。骨转移瘤发现频率因原发肿瘤的类型和所用检查手段不同而不同,虽然目前核素骨扫描是探测骨转移瘤最常用的手段,但其对骨转移瘤的诊断效能仍有一定限度。与99mTc-亚甲基二膦酸盐(99mTc-MDP)骨显像相比,18F-氟化钠(18F-NaF)和18F-氟代脱氧葡萄糖(18F-FDG) PET是分别从骨转移瘤产生的成骨反应和骨转移瘤本身的代谢活性角度进行评价的两种正电子示踪剂,结合PET的高度空间分辨率,特别是最近迅速应用于临床的PET-CT技术,使得正电子体层显像在全身骨骼恶性疾病评价上的准确性进一步提高。     

Radionuclide imaging of bone marrow disorders

Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as ^99mTc-nanocolloid, ^99mTc-sulphur colloid, ¹¹¹In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using ¹⁸F-FDG and ¹⁸F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed.     

The role of PET imaging in the management of patients with central nervous system disorders

PET will continue to play a critical role in both clinical and research applications with regard to CNS disorders. PET is useful in the initial diagnosis of patients presenting with CNS symptoms and can help clinicians determine the best course of therapy. PET studies can also be useful for studying the response to therapy. From the research perspective, the various neurotransmitter and other molecular tracers currently available or in development will provide substantial information about pathophysiologic process in the brain. As such applications become more widely tested, their introduction into the clinical arena will further advance the use of PET imaging in the evaluation and management of CNS disorders.     

Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET.

Radionuclide bone scanning (RNB) is considered to be the most practical screening technique for assessing the entire skeleton for skeletal metastases. However, RNB has been shown to be of lower sensitivity than MRI and CT in detecting osteolytic metastases. A prospective study was designed to evaluate the accuracy of planar RNB versus tomographic bone imaging with 18F-labeled NaF and PET (18F PET) in detecting osteolytic and osteoblastic metastases and its dependency on their anatomic localization. METHODS: Forty-four patients with known prostate, lung or thyroid carcinoma were examined with both planar RNB and 18F PET. A panel of reference methods including MRI of the spine, 1311 scintigraphy, conventional radiography and spiral CT was used as the gold standard. RNB and 18F PET were compared by a lesion-by-lesion analysis using a five-point score for receiver operating characteristic (ROC) curve analysis. RESULTS: 18F PET showed 96 metastases (67 of prostate carcinoma and 29 of lung or thyroid cancer), whereas RNB revealed 46 metastases (33 of prostate carcinoma and 13 of lung or thyroid cancer). All lesions found with RNB were also detected with 18F PET. Compared with 18F PET and the reference methods, RNB had a sensitivity of 82.8% in detecting malignant and benign osseous lesions in the skull, thorax and extremities and a sensitivity of 40% in the spine and pelvis. The area under the ROC curve was 0.99 for 18F PET and 0.64 for RNB. CONCLUSION: 18F PET is more sensitive than RNB in detecting osseous lesions. With RNB, sensitivity in detecting osseous metastases is highly dependent on anatomic localization of these lesions, whereas detection rates of osteoblastic and osteolytic metastases are similar. Higher detection rates and more accurate differentiation between benign and malignant lesions with 18F PET suggest the use of 18F PET when possible.     

18F-FDG PET与99Tcm-MDP骨显像在诊断肿瘤骨转移中的比较

恶性肿瘤发生骨转移将大大影响患者的生存率、降低患者的生活质量.PET和骨显像作为两种常见的评估全身骨骼情况的显像模式,能早期发现骨转移,进行肿瘤分期,帮助临床治疗.通过两种显像的原理,可以分析不同骨质破坏的病理类型的诊断差异和侧重点.除PET和骨显像之外,MRI也是灵敏度很高的影像学检查方法之一.此外,新型PET示踪剂的出现和PET-CT、SPECT-CT融合显像必将为核医学探测肿瘤骨转移提供新的价值.     

Detection of occult bone metastases of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography

Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans.     

18F-FDG PET与99Tcm-MDP骨显像在诊断肿瘤骨转移中的比较

恶性肿瘤发生骨转移将大大影响患者的生存率、降低患者的生活质量.PET和骨显像作为两种常见的评估全身骨骼情况的显像模式,能早期发现骨转移,进行肿瘤分期,帮助临床治疗.通过两种显像的原理,可以分析不同骨质破坏的病理类型的诊断差异和侧重点.除PET和骨显像之外,MRI也是灵敏度很高的影像学检查方法之一.此外,新型PET示踪剂的出现和PET-CT、SPECT-CT融合显像必将为核医学探测肿瘤骨转移提供新的价值.     

Quantitative studies of bone with the use of 18F-fluoride and 99mTc-methylene diphosphonate

This article discusses methods for quantifying bone turnover based on tracer kinetic studies of the short-lived radiopharmaceuticals 99mTc-MDP and 18F-fluoride. Measurements of skeletal clearance obtained by using these tracers reflect the combined effects of skeletal blood flow and osteoblastic activity. The pharmacokinetics of each tracer is described, together with some of the quantitative tests of skeletal function that have been described in the literature. The physiologic interpretation of quantitative measurements of bone obtained with the use of short half-life radionuclides is discussed, and the advantages and limitations of 99mTc-MDP and 18F-fluoride are compared and contrasted. Currently, 18F-fluoride dynamic positron emission tomography (PET) is the technique of choice for physiologically precise quantitative studies of bone. However, comparable data could probably be obtained by using 99mTc-MDP if methods for single photon emission computed tomography (SPECT) quantitation were improved.     

Advances in PET myocardial perfusion imaging: F-18 labeled tracers

Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI.     

The role of PET in lymphoma.

Malignant lymphomas are a heterogeneous group of diseases whose treatment and prognosis depend on accurate staging and evaluation of histologic features. The conventional imaging procedure is CT; however, nuclear medicine imaging has also had a prominent role. Single-photon imaging with 67Ga-citrate has been widely used for lymphomas. PET with 18F-FDG has gained a role in the staging and follow-up of lymphomas, largely replacing gallium as the nuclear medicine study of choice. 18F-FDG PET has proved useful in the staging and follow-up of Hodgkin's disease and non-Hodgkin's lymphoma (especially more aggressive types), and the widespread use of PET/CT has also increased the sensitivity and specificity. Its usefulness for the staging of slow-growing lymphomas has not been established. After the basics of staging and classification of lymphomas have been outlined, this article will review the role of 18F-FDG PET in the management of patients with lymphoma. PET tracers other than (18)F-FDG, such as positron-emitting isotopes of gallium and the cellular proliferation marker 18F-3'-deoxy-3'-fluorothymidine, will be discussed and future directions for PET in lymphoma proposed.     

Usefulness of 18F-FDG PET-directed skeletal biopsy for metastatic neoplasm

RATIONALE AND OBJECTIVES: Technium-99m methylene diphosphonate (99mTc-MDP) bone scintigraphy and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) are useful imaging modalities to detect skeletal metastases. Several other conditions such as infection, fractures, and arthritis can cause false-positive results with either modality. However, PET is felt to be more specific than bone scintigraphy for malignancy. Our objective was to investigate the value of PET scan compared with bone scintigraphy for directing biopsies in patients with suspected metastatic bone lesions. MATERIALS AND METHODS: Retrospective case series of subjects with undergoing skeletal biopsy of suspected metastases detected by 99mTc-MDP scintigraphy or 18F-FDG PET scan. Reference standards were pathologic reports and follow-up for 6 months. The diagnostic test performance measures of true positive (TP), false positive (FP), and positive predictive value (PPV) were calculated for each group. The PPV with 95% confidence intervals (CI) was compared using the Fisher exact test. RESULTS: There were a total of 68 subjects. PET-directed skeletal biopsies (n = 39) showed 35 TP, 4 FP, and an 89.7% PPV (95% CI: 75.7-97.1%). Bone scintigraphy directed biopsies (n = 29) had 21 TP, 8 FP, and 72.4 % PPV (95% CI: 52.7-82.7%). The PPV was not significantly different between the groups (P = .10). CONCLUSION: This study supports that PET can be used to effectively direct bone biopsies to confirm metastatic neoplasm and suggests that PET may provide incremental improvement to diagnostic yield over bone scintigraphy. The role of PET compared with bone scintigraphy for directing skeletal biopsies warrants further verification.     

18-fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation

During the past decade, 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) has rapidly evolved from a pure research modality to a clinical necessity. FDG-PET was introduced to determine the state of brain function in physiologic and pathologic states. Its use as a powerful tool to diagnose, stage, and monitor patients with a variety of malignancies has been truly revolutionary. However, FDG is a nonspecific tracer and it has been found to accumulate at sites of infection and inflammation. It is becoming evident that PET imaging will play a major role in the treatement of patients with suspected infection and inflammation. PET has been shown to be particularly valuable in the evaluation of chronic osteomyelitis, infected prostheses, sarcoidosis, fever of unknown origin, and acquired immunodeficiency syndrome. Because of its ability to quantitate the rate of FDG uptake, PET may prove to be a powerful modality for the monitoring of disease activity and response to therapy. Novel PET tracers are being tested for imaging infection and inflammation that may further enhance the role of this technique in the appropriate clinical setting. PET imaging to detect and characterize infection and inflammation may become a major clinical indication in the day-to-day practice of medicine.     

Bone metastases diagnosis possibilities in studies with the use of 18F-NaF and 18F-FDG

Scintigraphy of the skeletal system is performed mainly with the use of 99mTc-MDP. There are other radiopharmaceuticals showing affinity to bone lesions: 99mTc-MIBG, 201Tl, 131I (in the case of papillary or follicular thyroid cancers), and 99mTc (V) DMSA (in the case of medullary cancer). Currently, positron emitted radioisotopes are also used in clinical practice. It seems that 18F-NaF/PET is a highly sensitive and specific modality for detection of metastases and other bone lesions. Certain data concerning the role of 18F-FDG, 18F-choline, or 68Ga-DOTATATE can be found. The aim of this article is to review the role of 18F-NaF and 18F-FDG in diagnosis of bone metastases.     

Radionuclide imaging of infection

Although our understanding of microorganisms has advanced significantly and antimicrobial therapy has become increasingly available, infection remains a major cause of patient morbidity and mortality. The role of radionuclide imaging in the evaluation of the patient suspected of harboring an infection varies with the situation. For example, in the postoperative patient, radionuclide imaging is complementary to CT and is used to help differentiate postoperative changes from infection. In the case of the painful joint replacement, in contrast, radionuclide studies are the primary diagnostic imaging modality for differentiating infection from other causes of prosthetic failure. Several tracers are available for imaging infection: (99m)Tc-diphosphonates, (67)Ga-citrate, and (111)In- and (99m)Tc-labeled leukocytes. At the moment, in immunocompetent patients, labeled leukocyte imaging is the radionuclide procedure of choice for detecting most infections. There are, unfortunately, significant limitations to the use of labeled leukocytes. The in vitro labeling process is labor intensive, is not always available, and involves direct handling of blood products. For musculoskeletal infection, the need to frequently perform complementary marrow or bone imaging adds complexity and expense to the procedure and is an inconvenience to patients. Considerable effort has therefore been devoted to the search for alternatives to this procedure, including in vivo methods of labeling leukocytes, (18)F-FDG PET, and radiolabeled antibiotics. This article reviews the current status of nuclear medicine infection imaging and the potential of a murine monoclonal antigranulocyte antibody, fanolesomab, that is currently under investigation. Upon completion of this article, the reader will be familiar with the physical characteristics and uptake mechanisms of tracers currently approved for infection imaging, the indications for the uses of these tracers, and the characteristics and potential indications for a murine monoclonal antigranulocyte antibody under investigation.     

An introduction to Na(18)F bone scintigraphy: basic principles, advanced imaging concepts, and case examples

Na(18)F, an early bone scintigraphy agent, is poised to reenter mainstream clinical imaging with the present generations of stand-alone PET and PET/CT hybrid scanners. (18)F PET scans promise improved imaging quality for both benign and malignant bone disease, with significantly improved sensitivity and specificity over conventional planar and SPECT bone scans. In this article, basic acquisition information will be presented along with examples of studies related to oncology, sports medicine, and general orthopedics. The use of image fusion of PET bone scans with CT and MRI will be demonstrated. The objectives of this article are to provide the reader with an understanding of the history of early bone scintigraphy in relation to Na(18)F scanning, a familiarity with basic imaging techniques for PET bone scanning, an appreciation of the extent of disease processes that can be imaged with PET bone scanning, an appreciation for the added value of multimodality image fusion with bone disease, and a recognition of the potential role PET bone scanning may play in clinical imaging.     

Diagnostic value of <Superscript>18</Superscript>F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis

Purpose To retrospectively evaluate the diagnostic value of ¹⁸F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. Methods Thirty-three partial body ¹⁸F-FDG PET/CT scans were performed in 33 patients with trauma suspected of having chronic osteomyelitis. In 10 and 23 patients, infection was suspected in the axial and appendicular skeleton, respectively. In 18 patients, PET/CT was performed in the presence of metallic implants. Histopathology or bacteriological culture was used as the standard of reference. For statistical analysis, sensitivity, specificity and accuracy were calculated in relation to findings of the reference standard. Results Of 33 PET/CT scans, 17 were true positive, 13 true negative, two false positive and one false negative. Eighteen patients had chronic osteomyelitis and 15 had no osseous infection according to the reference standard. Sensitivity, specificity and accuracy for ¹⁸F-FDG PET/CT was 94%, 87% and 91% for the whole group, 88%, 100% and 90% for the axial skeleton and 100%, 85% and 91% for the appendicular skeleton, respectively. Conclusion ¹⁸F-FDG PET/CT is a highly sensitive and specific method for the evaluation of chronic infection in the axial and appendicular skeleton in patients with trauma. PET/CT allows precise anatomical localisation and characterisation of the infectious focus and demonstrates the extent of chronic osteomyelitis with a high degree of accuracy.