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Background: The appropriate use criteria considers cardiac stress testing within 2 years after percutaneous coronary intervention (PCI) to be rarely appropriate, unless prompted by symptoms or change in clinical status. Little is known about the patterns of cardiac stress testing after PCI in the single-payer Canadian healthcare system, where mechanisms for reimbursement are different from the United States., Methods and Results: Frequency and timing of cardiac stress testing within 2 years of PCI performed between April 2004 and March 2013 in Ontario, Canada, was determined from linked provincial databases. Subsequent rates of coronary angiography and revascularization after stress testing were ascertained. Of the 112 691 patients with PCI, 67 442 (59.8%) underwent at least 1 stress test, with 38 267 (34.0%) undergoing repeat stress testing (ie, >1 stress test) within 2 years. Patients who underwent stress testing were younger, had less medical comorbidities, were more likely to reside in urban areas, and had higher incomes. Spikes in incidence of repeat stress testing were observed at 3 to 4 months, 6 to 7 months, and 12 to 13 months after the prior stress test. Of those tested, only 5.9% underwent subsequent coronary angiography, and only 3.1% underwent repeat revascularization within 60 days of stress testing., Conclusions: More than half of all patients undergo cardiac stress testing within 2 years of PCI, with one third undergoing repeat stress tests. Only 1 of 30 tested patients underwent repeat revascularization. These findings reinforce the appropriate use criteria recommendations against routine stress testing after PCI. Further work is needed to aid with the selection of patients most likely to benefit from stress testing after PCI., (© 2017 American Heart Association, Inc.)

This review summarizes key imaging studies that were presented in the American Heart Association Scientific Sessions 2016 related to the fields of nuclear cardiology, cardiac computed tomography, cardiac magnetic resonance, and echocardiography. This bird's eye view will inform readers about multiple studies from these different modalities. We hope that this general overview will be useful for those that did not attend the conference as well as to those that did since it is often difficult to get exposure to many abstracts at large meetings. The review, therefore, aims to help readers stay updated on the newest imaging studies presented at the meeting.

"A quick glance at selected topics in this issue" aims to highlight selected articles and provide a quick review to the readers.

Although molecular imaging has had a dramatic impact on diagnostic imaging, it has only recently begun to be integrated into interventional procedures. Its significant impact is attributed to its ability to provide noninvasive, physiologic information that supplements conventional morphologic imaging. The four major interventional opportunities for molecular imaging are, first, to provide guidance to localize a target; second, to provide tissue analysis to confirm that the target has been reached; third, to provide in-room, posttherapy assessment; and fourth, to deliver targeted therapeutics. With improved understanding and application of(18)F-FDG, as well as the addition of new molecular probes beyond(18)F-FDG, the future holds significant promise for the expansion of molecular imaging into the realm of interventional procedures., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Competing Interests: The department of Cardiology of the Leiden University Medical Center received research grants from Edwards Lifesciences, Medtronic, Biotronik, and Boston Scientific.

Over the last two decades, molecular imaging has been established as a valuable technology, aiming at visualization and characterization of biochemical processes on a molecular level in isolated cells, tissues and higher organisms. Within the wide scope of the various imaging techniques, dual-labelled modalities for nuclear (PET, SPECT) and near-infrared fluorescence (NIRF) imaging show promise owing to their comparable detection sensitivity. Novel materials offer excellent prospects for the development of new non-invasive strategies of early diagnosis and efficient monitoring of therapeutic treatments. In the field of cancer medicine, the combination of different imaging techniques such as PET/SPECT and OI for tracking down tumours and metastases, and subsequent image-guided surgery for tumour resection is particularly attractive. This review focuses on the development of promising dual-labelled agents to be applied in bimodal nuclear/optical imaging, combining radionuclides and fluorescent dyes. The discussion encompasses modular ligands as well as nanoscale systems, including antibodies and their fragments.

Nuclear cardiology imaging tests are widely performed in Japan as clinical practice. The Japanese nuclear cardiology community has developed new diagnostic imaging tests using (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid, (123)I-metaiodobenzylguanidine, and (18)F-fluorodeoxyglucose PET for detecting cardiac involvement in sarcoidosis. These tests have become popular worldwide. The Japanese Circulation Society and the Japanese Society of Nuclear Cardiology have published clinical imaging guidelines showing indications and standards for the new imaging tests. JSNC is currently striving to improve the standard of clinical practice and is promoting research activities.

In recent years there has been methodological improvement in established nuclear medicine procedures, such as renal and skeletal scintigraphy and new very specific probes for treatment and diagnosis of urological diseases have been introduced into the clinical routine. New diagnostic methods, such as positron emission tomography (PET) using prostate-specific membrane antigen (PSMA) ligands for highly accurate tumor localization in recurrent prostate cancer have become available in many centers. The very high and selective accumulation of these PSMA ligands in tumor tissue has shown promising therapeutic results. Moreover, since 2013 a new radiopharmaceutical agent, radium-223 dichloride, has been approved for treatment of symptomatic bone metastases of prostate cancer. Better knowledge of indications, benefits and limitations of these procedures will help clinicians to adequately introduce them into patient management. This article summarizes the state of the art in established nuclear medicine procedures for urological disorders and also reports on new diagnostic and therapeutic possibilities.

Nuclear medicine imaging provides valuable functional information that complements information obtained with anatomic imaging techniques in the evaluation of patients with specific acute clinical manifestations. Nuclear medicine studies are most often used in conjunction with other imaging modalities and as a problem-solving tool. Under certain circumstances a nuclear medicine study may be indicated as the first-line imaging modality, as in the case of renal scintigraphy for transplant dysfunction in the early postoperative period. Nuclear imaging may be preferred when a conventional first-line study is contraindicated or when it is important to minimize radiation exposure. The portability of nuclear imaging offers particular advantages for the evaluation of critically ill patients whose clinical condition is unstable and who cannot be safely transported out of the intensive care unit. The ability to visualize physiologic and pathophysiologic processes over relatively long time periods without adding to the patient's radiation exposure contributes to the high diagnostic sensitivity of several types of nuclear medicine studies. Viewing the acquired images in the cine mode adds to the value of these studies for diagnosing and characterizing dynamic abnormalities such as intermittent internal bleeding and bile or urine leakage. In this pictorial review, the spectrum of nuclear medicine studies commonly performed in the acute care setting is reviewed according to body systems and organs, with detailed descriptions of the indications, technical considerations, findings, and potential pitfalls of each type of study. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.332125098/-/DC1.

Objectives: We evaluated temporal trends and geographic variation in choice of stress testing modality after percutaneous coronary intervention (PCI), as well as associations between modality and procedure use after testing., Background: Stress testing is frequently performed post-PCI, but the choices among available modalities (electrocardiography only, nuclear, or echocardiography; pharmacological or exercise stress) and consequences of such choices are not well characterized., Methods: CathPCI Registry(®) data were linked with identifiable Medicare claims to capture stress testing use between 60 and 365 days post-PCI and procedures within 90 days after testing. Testing rates and modality used were modeled on the basis of patient, procedure, and PCI facility factors, calendar quarter, and Census Divisions using Poisson and logistic regression. Post-test procedure use was assessed using Gray's test., Results: Among 284,971 patients, the overall stress testing rate after PCI was 53.1 per 100 person-years. Testing rates declined from 59.3 in quarter 1 (2006) to 47.1 in quarter 4 (2008), but the relative use of modalities changed little. Among exercise testing recipients, adjusted proportions receiving electrocardiography-only testing varied from 6.8% to 22.8% across Census Divisions; and among exercise testing recipients having an imaging test, the proportion receiving echocardiography (versus nuclear) varied from 9.4% to 34.1%. Post-test procedure use varied among modalities; exercise electrocardiography-only testing was associated with more subsequent stress testing (13.7% vs. 2.9%; p < 0.001), but less catheterization (7.4% vs. 14.1%; p < 0.001) than imaging-based tests., Conclusions: Modest reductions in stress testing after PCI occurring between 2006 and 2008 cannot be ascribed to trends in use of any single modality. Additional research should assess whether this trend represents better patient selection for testing or administrative policies (e.g., restricted access for patients with legitimate testing needs). Geographic variation in utilization of stress modalities and differences in downstream procedure use among modalities suggest a need to identify optimal use of the different test modalities in individual patients., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Noninvasive molecular imaging approaches include nuclear, optical, magnetic resonance imaging, computed tomography, ultrasound, and photoacoustic imaging, which require accumulation of a signal delivered by a probe at the target site. Monoclonal antibodies are high affinity molecules that can be used for specific, high signal delivery to cell surface molecules. However, their long circulation time in blood makes them unsuitable as imaging probes. Efforts to improve antibodies pharmacokinetics without compromising affinity and specificity have been made through protein engineering. Antibody variants that differ in antigen binding sites and size have been generated and evaluated as imaging probes to target tissues of interest. Fast clearing fragments, such as single-chain variable fragment (scFv; 25 kDa), with 1 antigen-binding site (monovalent) demonstrated low accumulation in tumors because of the low exposure time to the target. Using scFv as building block to produce larger, bivalent fragments, such as scFv dimers (diabodies, 50 kDa) and scFv-fusion proteins (80 kDa minibodies and 105 kDa scFv-Fc), resulted in higher tumor accumulation because of their longer residence time in blood. Imaging studies with these fragments after radiolabeling have demonstrated excellent, high-contrast images in gamma cameras and positron emission tomography scanners. Several studies have also investigated antibody fragments conjugated to fluorescence (near infrared dyes), bioluminescence (luciferases), and quantum dots for optical imaging and iron oxides nanoparticles for magnetic resonance imaging. However, these studies indicate that there are several factors that influence successful targeting and imaging. These include stability of the antibody fragment, the labeling chemistry (direct or indirect), whether critical residues are modified, the number of antigen expressed on the cell, and whether the target has a rapid recycling rate or internalizes upon binding. The preclinical data presented are compelling, and it is evident that antibody-based molecular imaging tracers will play an important future role in the diagnosis and management of cancer and other diseases., (Copyright 2010 Elsevier Inc. All rights reserved.)

Positron emission tomography (PET) is playing an increasingly important role in the diagnosis, staging, and monitoring response to treatment in a variety of cancers. Recent efforts have focused on immuno-PET, which uses antibody-based radiotracers, to image tumors based on expression of tumor-associated antigens. It is postulated that the specificity afforded by antibody targeting should both improve tumor detection and provide phenotypic information related to primary and metastatic lesions that will guide therapy decisions. Advances in antibody-engineering are providing the tools to develop antibody-based molecules with pharmacokinetic properties optimized for use as immuno-PET radiotracers. Coupled with technical advances in the design of PET scanners, immuno-PET holds promise to improve diagnostic imaging and to guide the use of targeted therapies. An overview of the preclinical immuno-PET studies in cancer models is reviewed here., (Copyright 2010 Elsevier Inc. All rights reserved.)

Molecular imaging is a new and evolving field that employs a targeted approach to noninvasively assess biologic processes in vivo. By assessing key elements in specific cellular processes prior to irreversible end-organ damage, molecular tools will allow for earlier detection and intervention, improving management and outcomes associated with cardiovascular diseases. The goal of those working to expand this field is not just to provide diagnostic and prognostic information, but rather to guide an individual's pharmacological, cell-based, or genetic therapeutic regimen. This article will review molecular imaging tools in the context of our current understanding of biological processes of the myocardium, including angiogenesis, ventricular remodeling, inflammation, and apoptosis. The focus will be on radiotracer-based molecular imaging modalities with an emphasis on clinical application. Though this field is still in its infancy and may not be fully ready for widespread use, molecular imaging of myocardial biology has begun to show promise of clinical utility in acute and chronic ischemia, acute myocardial infarction, congestive heart failure, as well as in more global inflammatory and immune-mediated responses in the heart-like myocarditis and allogeneic cardiac transplant rejection. With continued research and development, molecular imaging promises to be an important tool for the optimization of cardiovascular care.

The successful management of prostate cancer requires early detection, appropriate risk assessment, and optimum treatment. An unmet goal of prostate cancer imaging is to differentiate indolent from aggressive tumors, as treatment may vary for different grades of the disease. Different modalities have been tested to diagnose, stage, and monitor prostate cancer during therapy. This review briefly describes the key clinical issues in prostate cancer imaging and therapy and summarizes the various new imaging modalities and agents in use and on the horizon.

Molecular imaging tools, both equipment and agents, continue to improve and evolve, offering multimodality imaging with greater sensitivity and high-resolution of biological processes in real time. This review summarizes some of these recent developments in preclinical hardware, wetware and software, and their impact on drug development. The focus is on the advances in non-invasive small animal imaging such as positron emission tomography (PET), computed tomography (CT) and solid state detectors in single photon emission tomography (SPECT), which, when combined with labeled tracers serving as biomarkers and functional probes in vivo, are demonstrating the potential to accelerate our understanding of disease and help select drug candidates for development.

The role that imaging plays as a biomarker in the discovery and development of novel therapies has grown in recent years. Imaging is now a widely used in both the preclinical and clinical stages of development, close attention is now paid to the translational relevance of imaging data in an effort to make key decisions earlier. This article describes the use of imaging as a biomarker to demonstrate proof of target, mechanism, or efficacy. Examples are provided to show the types of information that can be gathered and a sense of the size of clinical trial that is required to obtain data for each category.

Since the advent of single photon emission computerized tomography (SPECT) and positron emission tomography (PET) various chemical ligands have been labeled with radionuclides and evaluated as tracer compounds in animal models to ascertain their suitability as potential radiopharmaceuticals for humans. In the absence of a defined algorithm to predict the diagnostic efficacy of a radiopharmaceutical, any new radioligand has to undergo preclinical evaluation even if it has excellent in vitro properties. Until now few studies have produced pharmacokinetic data that could be translated from animal models directly to humans. The purpose of this review is to highlight some critical aspects to consider during the development and validation phase of a new radiopharmaceutical. Interspecies differences and the absence of knowledge of physiological mechanism can become challenging drawbacks for obtaining a successful radiopharmaceutical. In this context, the influence of ABC transporters in neuroimaging, the effect of plasma protein binding and the consequence of anesthesia with reference to interspecies differences will be discussed with illustrative examples.

A promising role of cellular therapies in cancer treatment is reflected by the constantly growing number of clinical trials with adoptively transferred cells. Direct and indirect cell labeling for the nuclear imaging of transferred cells has been proven reliable for imaging adoptive cellular therapies. Both methods show their advantages and limitations. Direct labeling is a relatively easy, inexpensive, and well-established methodology. Indirect labeling using a reporter gene imaging paradigm allows for reliable, stable, and harmless visualization of cellular trafficking, persistence, proliferation, and function at the target site. It is expected that new human-derived reporter genes will be rapidly translated into clinical applications that require repetitive imaging for the effective monitoring of various genetic and cellular therapies.

Purpose: The aim of this study was to examine the effects of self-referral by comparing recent trends in payments and utilization rates for radionuclide myocardial perfusion imaging (MPI) among radiologists and cardiologists between 1998 and 2006., Materials and Methods: Nationwide Medicare Part B claims databases for 1998 through 2006 were used. The 4 primary MPI codes were selected. Using Medicare's physician specialty codes, physician providers were identified as radiologists, cardiologists, or other physicians. Payments for MPI to the 3 groups were tracked over the study period. Trends in utilization rates in both hospital and private office settings were also compared among the 3 groups. In addition, utilization trends were studied for related procedures, such as stress echocardiography (SE) and invasive diagnostic coronary angiography (CA)., Results: Between 1998 and 2006, Medicare Part B payments to radiologists for MPI increased from $72.6 million to $84.0 million (+16%), while among cardiologists, payments increased from $242.6 million to $972.0 million (+301%). Private office utilization rates per 1,000 Medicare beneficiaries increased by 215% among cardiologists, compared with 32% among radiologists. In hospital settings, the rate changes were much more modest. Hospital utilization rates were consistently higher among radiologists than cardiologists; in hospital settings in 2006, the rate was 15.3 per 1,000 among radiologists, compared with 11.8 per 1,000 among cardiologists. Between 1998 and 2006, the utilization rate for SE among cardiologists increased by 20%, and the rate for diagnostic CA among cardiologists also increased by 20%., Conclusion: In recent years, there have been very sharp increases in the costs and utilization of MPI among cardiologists compared with radiologists. Most of the growth occurred in cardiologists' private offices. In hospital settings, radiologists still do more MPI examinations than cardiologists. Because MPI is a highly reimbursed procedure and there is no evidence that coronary disease is increasing in frequency in the Medicare population, this trend raises a concern about inappropriate self-referral. This is particularly true in view of the facts that the utilization of a competing procedure such as SE also continues to increase among cardiologists and that MPI is not substituting for an invasive procedure such as diagnostic CA.

Breast cancer is the most common non-skin type of cancer and the second leading cause of cancer mortality in women. Advances in diagnosis and treatment have led to declines in mortality, despite an increase in breast cancer incidence. An advancing array of both local and systemic therapy options has led to increasingly individualized treatment. Imaging plays a key role in detecting breast cancer and directing its therapy. This continuing education article provides a comprehensive review of current and future radiotracer imaging methods applied to breast cancer, in the context of breast cancer management strategies and other nonnuclear imaging methods. Part 1 of the review provided an overview of clinical and biologic considerations in breast cancer and covered radionuclide imaging for detection and staging. Part 2 covers radionuclide imaging of breast cancer response to therapy, other clinical indications for radionuclide breast cancer imaging, and future directions, including molecular imaging.

Computed tomography is not the most frequent radiologic imaging procedure, but is arguably the most important in terms of clinical impact. CT is used extensively for emergencies, cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, orthopedic and other applications -often as the first and only imaging procedure needed for diagnosis. The chances are very high that a patient will have a CT scan in the emergency department, as an outpatient or as an inpatient for a multitude of indications - pain, trauma, suspected infection or malignancy, and frequently to investigate symptoms such as pain, or to answer a question raised by another abnormal test, such as an EKG abnormality or ultrasound finding. Despite the universality of CT in hospitals and clinics as well as free-standing imaging centers, the technology continues to evolve with greater coverage, faster acquisition and multienergy sources or detectors. The most demanding imaging applications are cardiovascular, where complex motion and small morphologic features coexist, so imaging methods that are very satisfactory elsewhere in the body may not be successful. Clinical CT scanning consists of administering toxic materials, e.g., contrast media, often monitoring the EKG and illuminating the body with high brightness x-rays. Larger area detectors and higher acquisition rates are welcome improvements, but don't solve all of the problems encountered with scan variability due to respiratory, random body, and cardiac motion, especially in a spectrum of patients from infant to massively obese adult sizes (< 1 kg to 250 kg or more). The challenges and pitfalls in CT will be delineated and evaluated relative to current and future technology.

We compare and contrast the development of optical molecular imaging techniques with nuclear medicine with a didactic emphasis for initiating readers into the field of molecular imaging. The nuclear imaging techniques of gamma scintigraphy, single-photon emission computed tomography, and positron emission tomography are first briefly reviewed. The molecular optical imaging techniques of bioluminescence and fluorescence using gene reporter/probes and gene reporters are described prior to introducing the governing factors of autofluorescence and excitation light leakage. The use of dual-labeled, near-infrared excitable and radio-labeled agents are described with comparative measurements between planar fluorescence and nuclear molecular imaging. The concept of time-independent and -dependent measurements is described with emphasis on integrating time-dependent measurements made in the frequency domain for 3-D tomography. Finally, we comment on the challenges and progress for translating near-infrared (NIR) molecular imaging agents for personalized medicine.

The objective of cardiac stress testing is to detect coronary artery disease (CAD) and to prevent future adverse events, such as myocardial infarction or death. The progression from electrocardiographically based stress testing to current SPECT and PET technologies has brought improvements in diagnostic efficacy and resolution. Myocardial perfusion imaging facilitates management of CAD in elective and acute settings by providing valuable diagnostic and prognostic information. Hybrid PET/CT and SPECT/CT systems impart complementary information of coronary anatomy and its physiologic significance on blood flow reserve. In the current era, diagnosis and treatment of cardiovascular disease is increasingly defined by underlying molecular and genomic aberrations rather than by clinical signs and symptoms alone. Nuclear imaging is uniquely primed to exploit the targeting of expressed cell-surface molecules and intracellular processes of cardiovascular disease and to foster the development of innovative therapeutic interventions in the future.

Aim: This second survey was to deliver further information on myocardial perfusion scintigraphy (MPS) in Germany in 2006., Method: 351 questionnaires were evaluated: 207 private practices (PP), 117 hospitals (HO), 27 from university hospitals (UH)., Results: MPS of 106 331 patients were reported, 85% were investigated with (99m)Tc-perfusion tracers. 74% [2005 = 72%] were performed in PP, 17% [2005 = 15%] in HO and 9% [2005 = 13%] in UH. PP, which participated in 2005 and 2006, demonstrated an increase by 3,9% (HO 0%, UH - 13,0%). The type of stress was pharmacological in 27% [2005 = 22%]; 54% adenosine (of these 29% with exercise), 37% dipyridamole (of these 56% with exercise), and 9% dobutamine. Gated SPECT was performed in 42% [2005 = 36%] of all rest- and in 39% [2005 = 32%] of all stress MPS. An attenuation correction was used by 69 [2005 = 78] institutions. 40% of all MPS were performed in patients suspected to have CAD. 24% of all institutions reported changes in the use of MPS by competing methods., Conclusion: There is a small increase of MPS between 2005 and 2006 despite competing methods. Gated SPECT has experienced more acceptance. Suspicion of CAD is an important indication of MPS. In order to tap the full potential of MPS a gated SPECT should be performed routinely.

The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies; (c) and assessments of endogenous molecular events using different inducible reporter gene imaging systems.

Echocardiography, magnetic resonance imaging and, more recently, multidetector computed tomography, have led to major advances in noninvasive image assessment of anatomy in pediatric cardiology. The radionuclide methods often lack sufficient resolution to precisely characterize complex morphology in congenital heart lesions. However, these methods provide an accurate and reproduceable quantitative assessment of the physiological consequences of structural heart disease. These unique capabilities will continue to assure ongoing clinical relevance of radionuclide methodology, as is the case in the assessment of heart disease in adult cardiology.

Introduction: In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, "reporter genes" transferred into cell nuclei encode for a protein that retains a complementary "reporter probe" of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy., Conclusion: Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy.