Positron Emission Tomography Techniques Research Articles

Multi-centre prospective assessment of accuracy and impact on management of positron emission tomography (PET) in esophageal and gastroesophageal junction cancers (EC). Australian PET Data Collection Project

4534 Background: In localized EC, radical surgery may be curative. This study evaluated PET and conventional imaging techniques (CI) for staging, and the potential impact of PET on management and prognosis of EC. Methods: Subjects had confirmed EC (SCC or adenocarcinoma), were fit for investigation and surgery and/or chemoradiotherapy and had no unequivocal distant metastatic disease clinically or by CT and endoscopy at presentation. Sensitivity, including N and M staging of pre-operative CT, PET and endoscopic ultrasound (EUS) and clinical impact of confirmation or detection of metastases on intent (curative or palliative) were recorded. Management changes, including radiotherapy field determined by new information from PET, were recorded. Variables, including standardized uptake value (SUV) were compared with progression-free survival (PFS.) Results: 129 patients (104 male), mean age 66 (range 36- 87) were evaluated. 127 of 129 primary lesions were detected. In 41% of patients, PET detected a total of 148 additional lesions, 75 regional lymph nodes, 72 distant metastases and 1 second EC primary. 22% of patients were upstaged from M0 to M1. CT detected regional and distant metastases in 57% and 0% (entry criterion), PET in 70% and 44%. Of 20 patients who had EUS, it detected regional metastases in 67%, PET in 33%.The number of patients intended to be treated palliatively increased from 10 pre- to 32 post-PET. Of patients with curative management intent based on PET 34% progressed in 12 months, with palliative intent 59%. Significant changes in management (high or medium impact) occurred in 38%. The PFS of 54 patients below and 54 above the median SUV(8) was no different (p=0.79) Conclusions: PET influenced management in 38% of patients with EC already studied by CI. No significant financial relationships to disclose.

Fusion of Positron Emission Tomography (PET) and Gene Array Data: A New Approach for the Correlative Analysis of Molecular Biological and Clinical Data

The combined assessment of data obtained by positron emission tomography (PET) and gene array techniques provide new capabilities for the interpretation of kinetic tracer studies. The correlative analysis of the data helps to detect dependencies of the kinetics of radiotracer on gene expression. Furthermore, gene expression may be predicted using regression functions if a significant correlation exists, which raises new aspects regarding the interpretation of dynamic PET examinations. The development of new radiopharmaceuticals requires the knowledge of the enhanced expression of genes, especially genes controlling receptors and cell surface proteins. The GenePET program facilitates an interactive approach together with the use of key words to identify possible targets for new radiopharmaceuticals.

Calculation of the positron distribution from 15O nuclei formed in nuclear reactions in human tissue during proton therapy

To measure and verify the dose distribution within a patient during proton therapy, indirect methods must be used. One such method is to use positron emission tomography (PET), which takes advantage of the nuclear reactions that take place between protons and nuclei in the tissue. The dominant nuclear reaction in human muscle tissue involves oxygen nuclei and produces radioactive oxygen-15. Oxygen-15 decays through positron emission, and it is these positrons that go on to annihilate that produce the signal used in the PET technique. Finding the distribution of annihilation points, however, is not analogous to finding the proton dose distribution. The oxygen-15 and positrons travel finite distances within the tissue, blurring the detected PET distribution from the desired proton distribution. Through Monte Carlo modelling, an analysis of the differences between the positron, oxygen-15 and proton distributions has been made. The program SRIM 2003 was used to find the correlation between the three distributions within simulated muscle tissue. Results show that the distal edge of the proton Bragg peak correlates with the detectable positron distribution, which is a section of the dose distribution of interest due to the steep dose gradient and position of adjacent critical structures.

Diaryliodonium salts: a solution to 3‐[18F]fluoropyridine

AbstractFluorine‐18 labelled fluoropyridines have found increasing application in the medical imaging technique of Positron Emission Tomography. The fluorine‐18 has largely been restricted to the 2‐ and 6‐position where its introduction may be readily achieved, from a range of appropriate precursors, by nucleophilic aromatic substitution using [18F]fluoride. However, fluorine at this position may be labile in vivo limiting the potential of the radiotracer. To date the more stable 3‐fluoro and 5‐fluoropyridines have not been exploited due to unsuitable methods of preparation. Pyridyliodonium salts provide a convenient way to overcome this restriction and allow the introduction of fluorine‐18, as fluoride, into the 3‐ or 5‐position. Copyright © 2007 John Wiley & Sons, Ltd.

Changes in brain 11C–nicotine binding sites in patients with mild Alzheimer’s disease following rivastigmine treatment as assessed by PET

Marked reduction in the cortical nicotinic acetylcholine receptors is observed in the brain of patients suffering from Alzheimer's disease (AD). Although cholinesterase inhibitors are used for symptomatic treatment of mild to moderate AD patients, numerous long-term treatment studies indicate that they might stabilize or halt the progression of the disease by restoring the central cholinergic neurotransmission. Thus, we used positron emission tomography (PET) technique as a sensitive approach to assess longitudinal changes in the nicotine binding sites in the brains of patients with AD. To evaluate changes in brain nicotinic binding sites in relation to inhibition level of cholinesterases in cerebrospinal fluid (CSF) and plasma and changes in cognitive performance of the patients in different neuropsychological tests after rivastigmine treatment. Ten mild AD patients received rivastigmine for 12 months. A dual-tracer PET model with administration of (15)O-water and (S)(-)(11)C-nicotine was used to assess (11)C-nicotine binding sites in the brain at baseline and after 3 and 12 months of the treatment. Cholinesterase activities in CSF and plasma were assessed colorimetrically. The (11)C-nicotine binding sites were significantly increased 12-19% in several cortical brain regions after 3 months compared with baseline, while the increase was not significant after 12 months of the treatment. After 3 months treatment, low enzyme inhibition in CSF and plasma was correlated with higher cortical (11)C-nicotine binding. The (11)C-nicotine binding positively correlated with attentional task at the 12-month follow-up. Changes in the (11)C-nicotine binding during rivastigmine treatment might represent remodeling of the cholinergic and related neuronal network.

The role of fluorine in medicinal chemistry

The small and highly electronegative fluorine atom can play a remarkable role in medicinal chemistry. Selective installation of fluorine into a therapeutic or diagnostic small molecule candidate can enhance a number of pharmacokinetic and physicochemical properties such as improved metabolic stability and enhanced membrane permeation. Increased binding affinity of fluorinated drug candidates to target protein has also been documented in a number of cases. A further emerging application of the fluorine atom is the use of 18F as a radiolabel tracer atom in the exquisitely sensitive technique of Positron Emission Tomography (PET) imaging. This short review aims to bring together these various aspects of the use of fluorine in medicinal chemistry applications, citing selected examples from across a variety of therapeutic and diagnostic settings. The increasingly routine incorporation of fluorine atom(s) into drug candidates suggests a bright future for fluorine in drug discovery and development. A major challenge moving forward will be how and where to install fluorine in a rational sense to best optimise molecular properties.

PET/CT imaging: what radiologists need to know

Positron emission tomography (PET)/computed tomography (CT) imaging is frequently requested in Oncology. Radiologists and nuclear medicine physicians are often asked to perform a panel of imaging examinations as part of the initial staging or follow-up of cancer patients. Medical imaging must therefore integrate polyvalent skills enabling imaging specialists to understand and interpret all types of images. In this context, PET imaging combined with non-enhanced CT, and diagnostic quality contrast-enhanced CT scan and optimisation of CT settings, is part of this multidisciplinary approach requiring the specific skills of a radiologist and a nuclear medicine physician. This approach must therefore be conducted in both directions: radiologists and nuclear medicine physicians should both know how to correlate PET and CT images, while preserving the specificities of each discipline. Radiologists need to be aware of several aspects of PET imaging: PET technology, the examination procedure and injection of iodinated contrast agent for high quality diagnostic CT, ideally followed by double interpretation of CT images, PET images and fused images. Radiologists should be familiar with PET imaging, as this procedure may be associated with several pitfalls and artefacts that need interpretation by a trained specialist. The authors analyse the examination technique of PET combined with non-enhanced and/or contrast-enhanced CT and the proposals for optimal interpretation of normal or pathological PET/CT fusion images.

Choline metabolism in cancer: implications for diagnosis and therapy

Magnetic resonance studies from the last 10 years have conclusively demonstrated that choline metabolism is altered in a wide variety of cancers. In cancer, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-containing compounds. This elevation is increasingly being used as an endogenous biomarker of cancer. Importantly, the enzymes and pathways resulting in these distinct alterations in phosphocholine and total choline may provide novel molecular targets for specific, targeted anticancer therapies. In this article, we have summarized some of the magnetic resonance spectroscopy and positron emission tomography techniques that are currently available, or will be in the near future, for choline metabolism-based diagnosis, staging and therapy assessment in cancer patients. This review also outlines currently known molecular alterations that cause the aberrant choline metabolite profile in cancers and concludes with a summary of recent research findings that may, in the future, lead to novel anticancer therapies targeting choline metabolism.

Visualizing lung function with positron emission tomography

Positron emission tomography (PET) provides three-dimensional images of the distributions of radionuclides that have been inhaled or injected into the lungs. By using radionuclides with short half-lives, the radiation exposure of the subject can be kept small. By following the evolution of the distributions of radionuclides in gases or compounds that participate in lung function, information about such diverse lung functions as regional ventilation, perfusion, shunt, gas fraction, capillary permeability, inflammation, and gene expression can be inferred. Thus PET has the potential to provide information about the links between cellular function and whole lung function in vivo. In this paper, recent advancements in PET methodology and techniques and information about lung function that have been obtained with these techniques are reviewed.

Masked Prosthetic Graft to Sigmoid Colon Fistula Diagnosed by 18-fluorodeoxyglucose Positron Emission Tomography

The diagnosis of low grade prosthetic graft infection or aorto-enteric fistula is difficult using conventional radiographic imaging modalities. We report a case of aorto-enteric fistula to the sigmoid colon diagnosed by the new technique of 18-fluorodeoxyglucose positron emission tomography.

Fundamentals of Neurogastroenterology: Basic Science

The focus of neurogastroenterology in Rome II was the enteric nervous system (ENS). To avoid duplication with Rome II, only advances in ENS neurobiology after Rome II are reviewed together with stronger emphasis on interactions of the brain, spinal cord, and the gut in terms of relevance for abdominal pain and disordered gastrointestinal function. A committee with expertise in selective aspects of neurogastroenterology was invited to evaluate the literature and provide a consensus overview of the Fundamentals of Neurogastroenterology textbook as they relate to functional gastrointestinal disorders (FGIDs). This review is an abbreviated version of a fuller account that appears in the forthcoming book, Rome III. This report reviews current basic science understanding of visceral sensation and its modulation by inflammation and stress and advances in the neurophysiology of the ENS. Many of the concepts are derived from animal studies in which the physiologic mechanisms underlying visceral sensitivity and neural control of motility, secretion, and blood flow are examined. Impact of inflammation and stress in experimental models relative to FGIDs is reviewed as is human brain imaging, which provides a means for translating basic science to understanding FGID symptoms. Investigative evidence and emerging concepts implicate dysfunction in the nervous system as a significant factor underlying patient symptoms in FGIDs. Continued focus on neurogastroenterologic factors that underlie the development of symptoms will lead to mechanistic understanding that is expected to directly benefit the large contingent of patients and care-givers who deal with FGIDs.

PET imaging of tumour hypoxia

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. [18F]Fluoromisonidazole-3-fluoro-1-(2 ′-nitro-1 ′-imidazolyl)-2-propanol ([18F]MISO) and Cu-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM)-positron emission tomography (PET), and blood oxygen level-dependent (BOLD)-magnetic resonance imaging (MRI) are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability; PET techniques are the primary focus of this review.

Los receptores para imidazolinas I2 como posible marcador de malignidad en tumores gliales humanos

To present the experimental data that support the hypothesis that the imidazoline I(2) receptors may be assessed as a biological marker to establish diagnosis and grade of human gliomas. Gliomas constitute the most important group of brain neoplasm in humans. In these tumours accurate histopathologic diagnosis is a first crucial prerequisite for patient treatment. However, current grading schemes are still limited by subjective histologic criteria. Therefore, the search for new molecular and biological markers of gliomas represents a crucial step. In this context, it has been reported a significant increase in I(2) density in human gliomas when compared with normal brain tissue and other intracranial non-glial tumours. Moreover, this increase seems to fit well with the degree of malignancy in human gliomas. Thus, in glioblastomas multiformes the I(2) density is 1.4 times higher than in anaplastic astrocytomas and 2.2 higher than in low-grade astrocytomas. The present results demonstrate that the measurement of the I(2) density by positron emission tomography techniques could be used in the future for grading and prognosis of human gliomas. This could avoid the current need for tumour biopsies in order to obtain a histopathologic diagnosis.

Imaging of Serotonin Mechanisms in Epilepsy

Advances in positron emission tomography (PET) techniques have allowed the measurement and imaging of neurotransmitter synthesis, transport, and receptor binding to be performed in vivo. With regard to epileptic disorders, imaging of neurotransmitter systems not only assists in the identification of epileptic foci for surgical treatment, but also provides insights into the basic mechanisms of human epilepsy. Recent investigative interest in epilepsy has focused on PET imaging of tryptophan metabolism, via the serotonin and kynurenine pathways, as well as on imaging of serotonin receptors. This review summarizes advances in PET imaging and how these techniques can be applied clinically for epilepsy treatment.

Blood Flow Imaging of the Brain: 50 Years Experience

Blood Flow Imaging of the Brain: 50 Years Experience

Reconstruction algorithm for single photon emission computed tomography and its numerical implementation

The modern imaging techniques of positron emission tomography and of single photon emission computed tomography are not only two of the most important tools for studying the functional characteristics of the brain, but they now also play a vital role in several areas of clinical medicine, including neurology, oncology and cardiology. The basic mathematical problems associated with these techniques are the construction of the inverse of the Radon transform and of the inverse of the so-called attenuated Radon transform, respectively. An exact formula for the inverse Radon transform is well known, whereas that for the inverse attenuated Radon transform was obtained only recently by R. Novikov. The latter formula was constructed by using a method introduced earlier by R. Novikov and the first author in connection with a novel derivation of the inverse Radon transform. Here, we first show that the appropriate use of that earlier result yields immediately an analytic formula for the inverse attenuated Radon transform. We then present an algorithm for the numerical implementation of this analytic formula, based on approximating the given data in terms of cubic splines. Several numerical tests are presented which suggest that our algorithm is capable of producing accurate reconstruction for realistic phantoms such as the well-known Shepp-Logan phantom.

Functional imaging with positron emission tomography in multiple system atrophy

Although the current guidelines for the clinical diagnosis of multiple system atrophy (MSA) do not require structural or functional brain imaging, investigations utilizing positron emission tomography (PET) have been helpful diagnostically in differentiating between MSA and primary autonomic failure; idiopathic Parkinson's disease; and sporadic olivopontocerebellar atrophy. These investigations have demonstrated different patterns of cerebral glucose utilization and of nigrostriatal projection abnormalities among these disorders and between the cerebellar and parkinsonian forms of MSA. Most of the studies have focused upon patients with well-established disease and none have examined the utility of PET imaging in early stage patients with follow-up of clinical course and autopsy verification to ensure accuracy of diagnosis and to determine the sensitivity and specificity of PET techniques for diagnosis. Recent PET studies have revealed denervation of myocardial post-ganglionic sympathetic neurons in some MSA patients, indicating that this disorder can affect the peripheral autonomic as well as the central nervous system. Investigations utilizing ligands to quantify central nervous system dopaminergic and cholinergic terminals have begun to provide insight into the neurochemical disorders that may underlie two of the sleep disturbances common in MSA, rapid eye movement sleep behavior disorder and obstructive sleep apnea.

Dissociation between global markers of bone formation and direct measurement of spinal bone formation in osteoporosis.

Regional bone metabolism measured using 18F-fluoride PET was assessed in 72 postmenopausal women classified as normal, osteopenic, or osteoporotic. Lower values of regional bone formation activity at the lumbar spine were seen in osteoporotic women, whereas global markers of bone formation were significantly increased. Evaluations of global bone remodeling have revealed that increased bone turnover is a feature of patients with osteoporosis. The noninvasive functional imaging technique of 18F-fluoride positron emission tomography (PET) allows the direct quantitative assessment of bone metabolism at specific sites in the skeleton, including the clinically important site of the lumbar spine. The aim of this study was to compare regional skeletal kinetics in 72 postmenopausal women (mean age, 61 years) classified as normal, osteopenic, or osteoporotic according to their BMD T score at the lumbar spine. Each woman had a dynamic PET scan of the lumbar spine after injection of 90 MBq 18F-fluoride ion and measurements of biochemical markers of bone formation and resorption. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were obtained by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K1) and the net plasma clearance of tracer to bone mineral (Ki), reflecting regional osteoblastic activity (ml/minutes/ml). Rate constants k2, k3, and k4, which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, were also measured. The net uptake of fluoride to the bone mineral compartment (Ki) was significantly lower in the osteoporotic group compared with both the osteopenic and normal groups, with a mean difference of 0.005 ml/minutes/ml (16.7%). The fraction of the tracer in the extravascular tissue space that underwent specific binding to bone mineral (k3/k2 + k3) was also significantly reduced in the women classified as osteoporotic. In contrast, levels of bone-specific alkaline phosphatase (BSALP) were significantly higher in the osteoporotic group compared with the normal and osteopenic groups by 35% and 27%, respectively. A significant negative correlation (r = -0.41) was observed between levels of BSALP and the fraction of the tracer that underwent specific binding to bone mineral. Lower values of Ki, a measurement of regional bone formation activity, were seen in women classified as osteoporotic, whereas levels of BSALP, a measure of global bone formation, were significantly increased. These findings are suggestive of increased global skeletal bone turnover in women with postmenopausal osteoporosis but with relatively reduced regional bone formation at the predominantly trabecular site of the lumbar spine.

Multimodality Imaging

Noninvasive “multimodal” in vivo imaging is not just becoming standard practice in the clinic, but is rapidly changing the evolving field of experimental imaging of genetic expression (“molecular imaging”). The development of multimodality methodology based on nuclear medicine (NM), positron emission tomography (PET) imaging, magnetic resonance imaging (MRI), and optical imaging is the single biggest focus in many imaging and cancer centers worldwide and is bringing together researchers and engineers from the far-ranging fields of molecular pharmacology to nanotechnology engineering. The rapid growth of in vivo multimodality imaging arises from the convergence of established fields of in vivo imaging technologies with molecular and cell biology. The cross-pollination of these disciplines has been accelerated in part by the establishment of the National Institutes of Health NCI P20 and P50 awards, for example, and by the sheer potential of the technology. Multimodality imaging is widely considered to involve the incorporation of two or more imaging modalities, usually within the setting of a single examination using, for example, dual- or triple-labeled optical or nuclear medicine “reporter” agents or by performing ultrasound or optical studies within the MR, single-photon emission computed tomography (SPECT), or x-ray computed tomography (CT) environment. Clinically, the best example of multimodality imaging is seen in the rapid evolution of PET-SPECT and PET-CT scanner hybrids. The PET modality has developed into perhaps the most used “multimodal” imaging method. The incorporation of PET into single, hybrid, and multimodality units to provide functional (typically from injected F-18DG studies) and anatomic information is becoming extremely popular,1–2 so much so that, for example, PET/CT hybrids can be found in outpatient screening centers located in shopping malls. The role of any multimodal imaging …

Principles and Practice of Positron Emission Tomography

AJR:180, May 2003 If you would like to review books for AJR , please send a cover letter stating your interest with a current curriculum vitae to Assistant Editor for Book Reviews, AJR , 101 S. Stratford Rd., Ste. 303, Winston-Salem, NC 27104. his book, written by Richard Wahl from the Department of Nuclear Medicine at Johns Hopkins University and assisted by multiple coauthors from other institutions, amply fulfills its goals of serving as both a reference and a starting point for physicians engaged in the performance of positron emission tomography (PET). In general, the text is well written and concise. With a few exceptions, the book is amply illustrated with well-labeled images of excellent quality. Each chapter concludes with extensive references for those interested in additional information regarding certain topics. The first four chapters deal exclusively with the production of PET radionuclides, the chemistry of radiopharmaceuticals, instrumentation, and data analysis and image processing. These chapters provide the basics in nuclear physics, radiopharmacy, and biochemistry that are crucial to understanding why PET works. The reader will also be introduced to how PET works in regard to the essential equipment, data acquisition, and analysis in the formation of the images. For the most part, this information is conveyed in an easy-to-understand manner to those who have limited recall of their basic science knowledge, although some of the mathematics regarding radiopharmaceutical kinetics is somewhat cumbersome. Chapter 5, which is divided into 14 sections, forms a major portion of the book and concerns oncologic applications of PET. Twelve sections deal with imaging of specific tumors and specific organ systems to which PET is applied. Protocols for imaging are described, and specific examples of positive findings are well illustrated, as are false-positive and false-negative findings, both of which are crucial to appropriate interpretation. The other sections describe using PET to determine tumor response to therapy and subsequent prognostic implications, both of which are becoming increasingly important in clinical practice. Also discussed is the adoption of CT–PET fusion techniques that allow more detailed localization of the abnormal radiotracer activity and more precise tumor staging. Chapters 6 and 7 describe the use of PET techniques in the diagnosis of both neurologic and psychiatric disorders. The general principles and rationale for performing these studies are described, including the use of FDG and other radiotracers such as carbon11 tagged to multiple ligands. This chapter is intellectually stimulating although primarily of academic interest at this time because of the current lack of reimbursement for these applications. These two chapters, although well written, are not as well illustrated as the prior chapters related to oncologic imaging. Chapter 8 consists of four sections devoted to different aspects of cardiac imaging. The first two sections describe the specific protocols, radiopharmaceuticals, physiologic principles, and interpretation of clinical imaging of myocardial perfusion and viability. The third section is devoted to oxidative metabolism and cardiac efficiency, and the final section deals with myocardial neurotransmitter imaging, an area of intense research at many institutions. In general, the cardiac sections are well written and informative but are also limited by relatively few clinical images. Chapter 9 is a short but important discussion of the applications of PET to inflammatory diseases and, more important, how to differentiate increased radiotracer uptake in inflammatory processes from tumors. This chapter is both well written and well illustrated. Chapter 10 focuses on the pediatric applications of PET, which, not surprisingly, is predominantly used for diagnosis and therapy of neoplasms. Protocols are described and multiple tumor applications are well illustrated. The final chapters, 11 and 12, are interesting and describe future applications related to PET drug development, the expected future imaging of gene expression and subsequent use in gene therapy planning, follow-up studies of treated tumors, and indicators of prognosis. In summary, I congratulate Dr. Wahl and his associates for creating, in my opinion, the most comprehensive and informative reference book on PET to date. This volume will serve well as both a reference work and a book that can be used on a daily basis by both novices and more experienced PET practitioners.