Tuberculosis remains a complicated problem. A lack of awareness accompanied by difficulty in diagnosis hinders the management of tuberculosis. Delayed management, particularly in osteoarticular regions, results in unnecessary procedures, including joint-sacrificing surgery.

Three cases of subclinical ankle joint tuberculosis without clear signs of tuberculosis were presented. The efficacy of technetium-99m-ethambutol scintigraphy in diagnosing early-stage tuberculous arthritis is reported.

The reports suggested that scintigraphy is recommended to diagnose subclinical tuberculous arthritis, especially in tuberculosis endemic regions.

Tuberculosis (TB) continues to be a major cause of death worldwide that can be effectively treated with timely diagnosis and treatment. With the advent of nuclear imaging techniques like ¹⁸Fluorine Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography (¹⁸F-FDG) PET/CT, the diagnosis of tuberculosis, particularly its extrapulmonary forms, has received great impetus in cases where microbiological confirmation cannot be achieved. Although detection of mycobacteria either by staining, culture or nucleic acid amplification techniques still form the gold standard of diagnosis, newer diagnostic techniques are always welcome in the field which can expedite clinical management. Use of radiolabeled antibiotics is one such evolving sphere which needs further research. Moving ahead from radiolabeled leukocytes, antibiotics are being increasingly focused upon to act as a vehicle to locate infectious lesions. Antibiotics like ciprofloxacin have been labeled with diagnostic radionuclides such as Technetium-99m (Tc-99m) and used to image many infectious diseases with encouraging results in TB. However, the nonspecific attributes of ciprofloxacin have hindered its growth to assist the diagnosis of TB. A novel approach would be to utilize ethambutol, a specific antitubercular agent, which has been found to be safe and effective in the diagnosis of TB in the available published studies. Ethambutol is known to be taken up specifically by tubercular lesions. This forms the basis of using Tc-99m labelled ethambutol for imaging TB lesions. An added advantage would be its ability to differentiate tubercular from malignant and fungal lung lesions that are the usual differentials in patients suspected of having TB. Most of the studies involving ethambutol have been done in skeletal TB and its validation in other forms of TB is still awaited. Recently the role of PET-CT has also been explored in human studies using ¹¹C Rifampicin to study the antibiotic uptake in tubercular lesions. This review summarizes the available evidence regarding diagnosis of TB by radiolabeled antibiotic imaging to emphasize the need for accelerated research in the fight against TB.

Diagnosis of deep-seated bacterial infection remains a serious medical challenge. The situation is becoming more severe with the increasing prevalence of bacteria that are resistant to multiple antibiotic classes. Early efforts to develop imaging agents for infection, such as technetium-99m (^99mTc) labeled leukocytes, were encouraging, but they failed to differentiate between bacterial infection and sterile inflammation. Other diagnostic techniques, such as ultrasonography, magnetic resonance imaging, and computed tomography, also fail to distinguish between bacterial infection and sterile inflammation. In an attempt to bypass these problems, the potent, broad-spectrum antibiotic ciprofloxacin was labeled with ^99mTc to image bacterial infection. Initial results were encouraging, but excitement declined when controversial results were reported. Subsequent radiolabeling of ciprofloxacin with ^99mTc using tricarbonyl and nitrido core, fluorine and rhenium couldn't produce robust infection imaging agent and remained in discussion. The issue of developing a robust probe can be approached by reviewing the broad-spectrum activity of ciprofloxacin, labeling strategies, potential for imaging infection, and structure-activity (specificity) relationships. In this review we discuss ways to accelerate efforts to improve the specificity of ciprofloxacin-based imaging.

Infection is ubiquitous. However, its management is challenging for both the patients and the health-care providers. Scintigraphic imaging of infection dates back nearly half a century. The advances in our understanding of the pathophysiology of disease at cellular and molecular levels have paved the way to the development of a large number of radiopharmaceuticals for scintigraphic imaging of infection. These include radiolabeling of blood elements such as serum proteins, white blood cells (WBCs), and cytokines, to name a few. Infectious foci have also been imaged using a radiolabeled sugar molecule by taking advantage of increased metabolic activity in the infectious lesions. Literature over the years has well documented that none of the radiopharmaceuticals and associated procedures that facilitate imaging infection are flawless and acceptable without a compromise. As a result, only a few compounds such as 99mTc-hexamethylpropyleneamineoxime, 18F-FDG, the oldest but still considered as a gold standard 111In-oxine, and, yes, even 67Ga-citrate in some countries, have remained in routine clinical practice. Nonetheless, the interest of scientists and physicians to improve the approaches to imaging and to the management of infection is noteworthy. These approaches have paved the way for the development of numerous, innovative radiopharmaceuticals to label autologous WBCs ex vivo or even those that could be injected directly to image infection or inflammation without direct involvement of WBCs. In this review, we briefly describe these agents with their pros and cons and place them together for future reference.

Tuberculosis (TB) still remains the world's endemic infection. TB affects the lungs and any part of the body other than the lung. The diagnosis of TB has not changed much over the decades. Ethambutol is one of the first line treatments for TB. It can be labeled using ^99mTc. ^99mTc-ethambutol will be accumulated in the site of TB lesion and can be imaged using gamma camera. The aim of this study was to evaluate the diagnostic value of ^99mTc-ethambutol scintigraphy in detecting and localizing of TB.

Retrospective cross-sectional study was done. Subjects were patients suspected of having TB infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4 h after injection of 370-555 MBq ^99mTc-ethambutol. ^99mTc-ethambutol scintigraphy was analyzed visually. The results were compared with that of histopathological or microbiological tests. Statistical analysis was done to determine the sensitivity, specificity, PPV, NPV and accuracy.

One hundred and sixty-eight subjects were involved in this study. There were 110 men and 58 women with mean age of 34.52 ± 11.94 years. There were concordance results in 156 (92.86%) and discordant in 12 (7.14%) subjects between ^99mTc-ethambutol scintigraphy and histopathological or microbiological result. The sensitivity, specificity, PPV, NPV and accuracy of ^99mTc-ethambutol scintigraphy in the diagnosis of pulmonary TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, for extra-pulmonary TB 95.5, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9, 83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in this study.

^99mTc-ethambutol scintigraphy is a useful diagnostic imaging technique to detect and localize intra- and extra-pulmonary TB. It is safe to be performed even in pediatric patient. Consuming ethambutol less than 2 weeks did not influence the result.

Diagnosis of deep-seated bacterial infection is difficult, as neither standard anatomical imaging nor radiolabeled, autologous leukocytes distinguish sterile inflammation from infection. Two recent imaging efforts are receiving attention: (1) radioactive derivatives of sorbitol show good specificity with Gram-negative bacterial infections, and (2) success in combining anatomical and functional imaging for cancer diagnosis has rekindled interest in 99mTc-fluoroquinolone-based imaging. With the latter, computed tomography (CT) would be combined with single-photon-emission-computed tomography (SPECT) to detect 99mTc-fluoroquinolone-bacterial interactions. The present minireview provides a framework for advancing fluoroquinolone-based imaging by identifying gaps in our understanding of the process. One issue is the reliance of 99mTc labeling on the reduction of sodium pertechnetate, which can lead to colloid formation and loss of specificity. Specificity problems may be reduced by altering the quinolone structure (for example, switching from ciprofloxacin to sitafloxacin). Another issue is the uncharacterized nature of 99mTc-ciprofloxacin binding to, or sequestration in, bacteria: specific interactions with DNA gyrase, an intracellular fluoroquinolone target, are unlikely. Labeling with 68Ga rather than 99mTc enables detection by positron emission tomography, but with similar biological uncertainties. Replacing the C6-F of the fluoroquinolone with 18F provides an alternative to pertechnetate and gallium that may lead to imaging based on drug interactions with gyrase. Gyrase-based imaging requires knowledge of fluoroquinolone action, which we update. We conclude that quinolone-based probes show promise for the diagnosis of infection, but improvements in specificity and sensitivity are needed. These improvements include the optimization of the quinolone structure; such chemistry efforts can be accelerated by refining microbiological assays.

Bacterial infections are still one of the main causes of patient morbidity and mortality worldwide. Nowadays, many imaging techniques, like computed tomography or magnetic resonance imaging, are used to identify inflammatory processes, but, although they recognize anatomical modifications, they cannot easily distinguish bacterial infective foci from non bacterial infections. In nuclear medicine, many efforts have been made to develop specific radiopharmaceuticals to discriminate infection from sterile inflammation. Several compounds (antimicrobial peptides, leukocytes, cytokines, antibiotics…) have been radiolabelled and tested in vitro and in vivo, but none proved to be highly specific for bacteria. Indeed factors, including the number and strain of bacteria, the infection site, and the host condition may affect the specificity of tested radiopharmaceuticals. Ciprofloxacin has been proposed and intensively studied because of its easy radiolabelling method, broad spectrum, and low cost, but at the same time it presents some problems such as low stability or the risk of antibiotic resistance. Therefore, in the present review studies with ciprofloxacin and other radiolabelled antibiotics as possible substitutes of ciprofloxacin are reported. Among them we can distinguish different classes, such as cephalosporins, fluoroquinolones, inhibitors of nucleic acid synthesis, inhibitors of bacterial cell wall synthesis and inhibitors of protein synthesis; then also others, like siderophores or maltodextrin-based probes, have been discussed as bacterial infection imaging agents. A systematic analysis was performed to report the main characteristics and differences of each antibiotic to provide an overview about the state of the art of imaging infection with radiolabelled antibiotics.