ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy.

OBJECTIVES: This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors. This document ensures safe handling of Lu-177 DOTATATE by the authorized users and safe management of affected patients. METHODS: The document was developed according to the systematic process developed by the American College of Radiology (ACR) and described on the ACR Web site (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards). The PP development was led by 2 ACR Committees on Practice Parameters (Nuclear Medicine and Molecular Imaging and Radiation Oncology) collaboratively with the American College of Nuclear Medicine, American Society of Radiation Oncology, and Society of Nuclear Medicine and Molecular Imaging. RESULTS: The Lu-177 DOTATATE PP reviewed pharmacology, indications, adverse effects, personnel qualifications, and required clinical evaluation before starting the treatment, as well as the recommended posttherapy monitoring, quality assurance, documentation, and appropriate radiation safety instructions provided in written form and explained to the patients. CONCLUSIONS: Lu-177 DOTATATE is available for therapy of inoperable and/or advanced GEP-NETs when conventional therapy had failed. It can reduce tumor size, improve symptoms, and increase the progression free survival. The PP document provides clinical guidance for authorized users to assure an appropriate, consistent, and safe practice of Lu-177 DOTATATE.

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy.

OBJECTIVES: This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors. This document ensures safe handling of Lu-177 DOTATATE by the authorized users and safe management of affected patients. METHODS: The document was developed according to the systematic process developed by the American College of Radiology (ACR) and described on the ACR Web site (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards). The PP development was led by 2 ACR Committees on Practice Parameters (Nuclear Medicine and Molecular Imaging and Radiation Oncology) collaboratively with the American College of Nuclear Medicine, American Society of Radiation Oncology, and Society of Nuclear Medicine and Molecular Imaging. RESULTS: The Lu-177 DOTATATE PP reviewed pharmacology, indications, adverse effects, personnel qualifications, and required clinical evaluation before starting the treatment, as well as the recommended posttherapy monitoring, quality assurance, documentation, and appropriate radiation safety instructions provided in written form and explained to the patients. CONCLUSIONS: Lu-177 DOTATATE is available for therapy of inoperable and/or advanced GEP-NETs when conventional therapy had failed. It can reduce tumor size, improve symptoms, and increase the progression free survival. The PP document provides clinical guidance for authorized users to assure an appropriate, consistent, and safe practice of Lu-177 DOTATATE.

The Utility of Hepatobiliary Scintigraphy Scans in the Tokyo Guidelines Era for Acute Cholecystitis.

BACKGROUND: Hepatobiliary Scintigraphy (HIDA) aids the diagnosis of acute cholecystitis (AC) but has limitations. We sought to design a model based on the Tokyo Guidelines 2018 (TG18) to predict HIDA results. METHODS: A retrospective review of patients who underwent a HIDA scan during the evaluation of AC was performed. Using logistic regression techniques incorporating the TG18 criterion and additional readily available patient characteristics, a prediction model was created to identify patients likely to test negative for acute cholecystitis by HIDA scan. RESULTS: In 235 patients with suspected AC, a HIDA scan was performed. Variables associated with positive HIDA results were male gender (RR 2.0 (CI 1.33-2.99), age (OR 1.02 (CI 1.01-1.04), right upper quadrant tenderness (RR 1.7 (CI 1.1-2.8)), clinical Murphy's sign (RR 2.2 (CI 1.5-3.4)), ultrasound findings suggestive of AC by any of its components (RR 3.2 (CI 1.6-6.5)), gallbladder wall thickening (RR 2.0 (CI 1.3-3.1)), and gallbladder distention (RR 1.9 (CI 1.3-2.9)). These variables allowed for creation of a model to predict HIDA results. The model predicted HIDA results in 36.9% of patients with an area under the curve of 0.81. CONCLUSIONS: In the era of TG18, HIDA is probably over utilized. We developed an accurate, simple model based on TG18 that identifies a group of patients for whom a HIDA scan is unnecessary to establish the diagnosis of AC.

The Utility of 18FDG PET/CT Versus Bone Scan for Identification of Bone Metastases in a Pediatric Sarcoma Population and a Review of the Literature.

BACKGROUND: Outcome of patients with osteosarcoma (OS) and Ewing sarcoma (EWS) is dependent on presence of metastases. Imaging guidelines for OS and EWS include radiographs, computed tomography (CT), and magnetic resonance imaging for primary tumor evaluation and CT chest and bone scintigraphy (BS) for metastatic detection. 18Fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT has become more common for disease evaluation, yet there is no consensus for its use in this population. OBJECTIVE: We aimed to compare identification of osseous metastases using BS versus 18FDG PET/CT in our patient population. We hypothesized that 18FDG PET/CT is more likely to detect osseous metastases both at diagnosis and relapse. MATERIALS AND METHODS: We performed retrospective chart reviews of pediatric sarcoma patients treated at our institution from 2008 to 2019. Paired BS and 18FDG PET/CT scans were reviewed. Review of the literature was also performed. RESULTS: Thirty-three patients had paired BS and 18FDG PET/CT during diagnosis or treatment. Fifteen patients had distant osseous metastases. In the OS cohort, 8/16 patients had osseous metastases; 100% of these patients were detected on 18FDG PET/CT and 75% on BS. Thirty-one bony lesions were seen on imaging in OS patients; 100% of these were identified on 18FDG PET/CT but only 29% on BS. In the EWS cohort, 6/15 patients had osseous metastases; 100% of these patients were detected on 18FDG PET/CT and 50% on BS. Eighteen bony lesions were seen on imaging in EWS patients; 94% of these were identified on 18FDG PET/CT, but only 28% on BS. CONCLUSION: For patients in our institution with OS or EWS, osseous metastases were more likely detected using 18FDG PET/CT.

Clinical Utility of 18F-FDG PET/CT in Staging Localized Breast Cancer Before Initiating Preoperative Systemic Therapy.

BACKGROUND: 18F-fluorodeoxyglucose PET/CT is recommended as an optional study in the current NCCN Clinical Practice Guidelines in Oncology for Breast Cancer after CT of the chest, abdomen, and pelvis with contrast and bone scan (CTBS) in stage IIA-IIIC breast cancer. We evaluated our experience with the use of PET/CT in this setting before beginning primary systemic therapy (PST) prior to planned surgery. METHODS: We performed medical record abstractions of all adult female patients with clinical stage IIA-IIIC breast cancer diagnosed at Montefiore Medical Center from January 1, 2014, through January 1, 2019, who underwent PET/CT before PST. We calculated the proportion of patients upstaged after PET/CT and examined the cost and radiation exposure associated with PET/CT compared with CTBS. RESULTS: A total of 195 patients with 196 breast cancers (bilateral disease in 1 patient) met the study inclusion criteria and had PET/CT as the first imaging study before PST. The overall upstaging rate for regional nodal metastasis and/or distant metastasis was 37% (73/196), including 24% for stage IIA (9/38), 39% for stage IIB (31/79), 54% for stage IIIA (22/41), 27% for stage IIIB (8/30), and 37% for stage IIIC (3/8). The overall upstaging rate for distant metastasis was 14% (27/196), including 0% for stage IIA, 13% for stage IIB (10/79), 22% for stage IIIA (9/41), 17% for stage IIIB (5/30), and 37% for stage IIIC (3/8). Medicare reimbursement rates were $1,604.37 for PET/CT and $1,679.94 for CTBS. The radiation dose for PET/CT was 14 mSv versus 21 mSv for CTBS. CONCLUSIONS: Approximately 37% of patients with clinical stage IIA-IIIC breast cancer who underwent PET/CT before PST showed more extensive disease, including 23% with more extensive nodal metastasis and 14% with distant metastasis. Given its high detection rate, comparable cost, lower radiation dose, and greater convenience, PET/CT should be considered as an alternative to CTBS rather than "optional" after CTBS, especially in patients who require an efficient and expeditious workup before initiating PST.

Nuclear Medicine Imaging in Fever of Unknown Origin: The New Paradigm.

Fever of Unknown Origin, or FUO, is a challenging condition for patients and clinicians. In up to 50% of cases, no diagnosis is established. Patient workup begins with comprehensive history, physical examination and laboratory tests. Radionuclide imaging has been a second-line procedure. Gallium-67 citrate, which accumulates in infection, inflammation, and tumor, was for many years, the radionuclide test of choice in the workup of FUO. The 24-72 hours between injection and imaging, relatively high radiation dose to patients, and suboptimal image quality are significant disadvantages; imaging results are variable. Although labeled leukocyte imaging accurately localizes infection, infections cause only about 20%-40% of all FUO's. In most cases, this test is not helpful in identifying the source of the fever. Fluorine-18-fluorodeoxyglucose (FDG) uptake is related to cellular glucose metabolism. Increased FDG uptake is present in numerous hypermetabolic conditions, including tumor, infection, and noninfectious inflammation. FDG positron emission tomography (PET) and PET/computed tomography (CT) have rapidly assumed an increasingly important role in the diagnostic workup of patients with FUO. FDG is especially useful for localizing lesions and areas of interest for further evaluation. In contrast to gallium and labeled leukocyte imaging, FDG contributes useful information in children with FUO. Initially utilized as a second-line diagnostic tool in patients with FUO, recent data indicate that FDG contributes more diagnostically useful information than anatomic imaging like ultrasound and CT, which leads to earlier institution of appropriate therapy. These findings suggest that FDG imaging should be performed earlier, rather than later, in the diagnostic evaluation of the patient with FUO.

Role of Nuclear Medicine for Diagnosing Infection of Recently Implanted Lower Extremity Arthroplasties.

Infection is an infrequent complication of lower extremity prosthetic joint surgery. Approximately one-third develop within 3 months (early), another third within 1 year (delayed), and the remainder more than 1 year (late) after surgery. Diagnosing prosthetic joint infection, especially in the early postoperative period during the first year, is challenging. Pain is almost always present. The presence of fever is variable, ranging from less than 5% to more than 40% of patients. Leukocytosis is a poor predictor of infection. After primary uncomplicated arthroplasty, the C-reactive protein remains elevated for up to 3 weeks. The erythrocyte sedimentation rate can remain elevated for up to 1 year. Although joint aspiration with culture, the definitive preoperative diagnostic procedure, is specific, its sensitivity is variable. Plain radiographs lack sensitivity and specificity. Radionuclide studies are useful for evaluating painful joint replacements, but data on their utility during the early postoperative period are limited. During the first year after arthroplasty insertion, the bone scan can exclude infection. It is a good "rule-out" test, but it is not reliable for "ruling in" infection. Gallium-67 accumulates in normally healing surgical incisions and in aseptic inflammation. With an accuracy of 60%-80% for diagnosing prosthetic joint infection, there is little role for this radiopharmaceutical for evaluating prosthetic joints, regardless of age. Although data about diagnosing prosthetic joint infection with 18F-FDG in the early postoperative period are lacking, uptake of this radiopharmaceutical in a variety of postoperative settings for variable time periods is well known. Furthermore, its utility for diagnosing prosthetic joint infection in general, after nearly 2 decades of investigation, remains to be established. Indium-111-labeled leukocytes do not accumulate in normally healing surgical wounds, and in combination with marrow imaging, the test is about 90% accurate for diagnosing prosthetic joint infection. Preliminary data indicate a comparable accuracy in the early postoperative period.

Relevance of focal osseous uptake on FDG PET with or without CT changes in oncology patients.

OBJECTIVE: To assess significance of focal FDG uptake in osseous structures, with and without CT correlate, in patients undergoing FDG PET/CT for oncological indications. METHODS: 57 patients with focally increased FDG activity in bones and a definite follow up were included. RESULTS: 85.2% of lesions without changes were found to be malignant. Sensitivity and PPV of a CT correlate in metastatic lesions was expectedly high, 62.9% and 86.7% respectively, however, the NPV was only 14.8%. CONCLUSION: Osseous foci are valuable in predicting metastatic disease even in the absence of low dose CT correlate.

The value of FDG-PET in the staging of gastric adenocarcinoma: A single institution retrospective review.

BACKGROUND: The value of FDG-PET in the staging of gastric adenocarcinoma (GA) has been subject to debate. METHODS: We performed a retrospective review of GA patients between 2006 and 2014 and identified those who had a CT and FDG-PET before initiating treatment. CT and FDG-PET images were analyzed by a blinded body radiologist and nuclear physician, respectively. Disease stage was assessed, looking at primary tumor (PT), locoregional (LLN) and distant lymph node disease (DLN), and metastasis (M). RESULTS: We identified 608 patients who had biopsy-proven GA and 207 (34.0%) had a CT and FDG-PET as part of their staging work-up. Of these, imaging from 166 (27.3%) patients was available for review. CT identified PT, LLN, DLN, and M in 120 (72.3%), 84 (50.6%), 25 (15.1%), and 32 (19.3%) patients, respectively; while FDG-PET identified PT, LLN, DLN, and M in 125 (75.3%), 78 (47.0%), 41 (24.7%), and 27 (16.3%) of patients, respectively. FDG-PET up-staged 31 (18.7%) patients while it down-staged 17 (10.2%) patients. Of patients who were up-staged, 20 (64.5%) developed progressive disease. CONCLUSIONS: Our findings support the use of FDG-PET as a valuable adjunct to CT in the staging of GA, as it changed the stage in 48 (28.9%) patients. J. Surg. Oncol. 2016;113:640-646. © 2016 Wiley Periodicals, Inc.

Radionuclide imaging of inflammation and infection in the acute care setting.

Although infection may be suggested by signs and symptoms such as fever, pain, general malaise, and abnormal laboratory results, imaging tests often are used to confirm its presence. Morphologic imaging tests identify structural alterations of tissues or organs that result from a combination of microbial invasion and the inflammatory response of the host. Functional imaging studies use minute quantities of radioactive material, which are taken up directly by cells, tissues, and organs, or are attached to substances that subsequently migrate to the region of interest. Bone scintigraphy is extremely sensitive and can be positive within 2 days after the onset of symptoms. With an accuracy of more than 90%, 3-phase bone scintigraphy is the radionuclide procedure of choice for diagnosing osteomyelitis in unviolated bone. In patients with acute renal failure, gallium imaging facilitates the differentiation of acute interstitial nephritis from acute tubular necrosis. Gallium imaging also is useful in the evaluation of pulmonary infections and inflammation. Many opportunistic infections affect the lungs, and a normal gallium scan of the chest excludes infection with a high degree of certainty, especially when the chest x-ray is negative. In the human immunodeficiency virus positive patient, lymph node uptake usually is associated with mycobacterial disease or lymphoma. Focal pulmonary parenchymal uptake suggests bacterial pneumonia. Diffuse pulmonary uptake suggests an opportunistic pneumonia. Gallium imaging provides useful information about other acute respiratory conditions, including radiation pneumonitis and hypersensitivity pneumonitis. In vitro labeled leukocyte imaging with indium-111 and technetium-99m labeled leukocytes is useful in various acute care situations. The test facilitates the differentiation of normal postoperative changes from infection and is useful for diagnosing prosthetic vascular graft infection. In inflammatory bowel disease, labeled leukocyte imaging is useful for initial screening, monitoring treatment response, detecting recurrent disease, and evaluating patients with discordant physical presentation and laboratory test results. Labeled leukocyte imaging, combined with bone marrow scintigraphy accurately diagnoses complicating osteomyelitis. Fluorine-18-fluorodeoxyglucose, imaging is rapidly completed and provides high-resolution images. This test is especially valuable in patients with fever of unknown origin, patients in septic shock, and mechanically ventilated patients suspected of harboring infection. Fluorine-18-fluorodeoxyglucose imaging also shows promise in inflammatory bowel disease.

Photomultiplier tube artifacts on 67Ga-citrate imaging caused by loss of correction floods due to an off-peak status of one head of a dual-head γ-camera.

UNLABELLED: γ-cameras use flood-field corrections to ensure image uniformity during clinical imaging. A loss or corruption of the correction data of one head of a dual-head camera can result in an off-peak artifactual appearance. We present our experience with the occurrence of such an incident on a (67)Ga scan. METHODS: A patient was referred for a whole-body (67)Ga scan to evaluate for causes of neutropenic fever. Whole-body planar and static images of the head, chest, abdomen, pelvis, and lower extremities in multiple projections were obtained. RESULTS: Whole-body images showed decreased image quality on the anterior view obtained with detector 1 and an unremarkable posterior image obtained with detector 2. A problem with detector 2 was suspected, and additional static images were obtained after rotation of the detector heads. The posterior images taken with detector 1 showed photomultiplier tube outlines. The anterior images taken with detector 2 showed improved count and image quality. It was later found that the uniformity map for detector 2 had been lost and that this software malfunction led to the resulting imaging problem. CONCLUSION: When artifacts with an off-peak appearance are seen on scintigraphic images, evaluation of possible causes should include not only isotope window settings but also an incorrect or corrupted uniformity map.

Decreased sensitivity of (18)F-fluorodeoxyglucose imaging in infection and inflammation.

Nuclear medicine plays an important role in the evaluation of inflammation and infection. Although (99m)Tc-methylene diphosphonate, (67)Ga-citrate, and in vitro labeled autologous leukocyte imaging are useful procedures, there are limitations to each of them. (18)F-fluorodeoxyglucose-positron-emission tomography (PET) and PET/computed tomography offer several advantages over conventional single-photon-emitting tracers and has proved to be a valuable addition to the nuclear medicine infection imaging armamentarium. PET provides high-resolution 3-dimensional images of the whole body that facilitates precise localization of abnormalities. Localization is enhanced with PET/computed tomography. Fluorodeoxyglucose, for the most part, is exquisitely sensitive with a high negative predictive value. In general, the limiting factor of the test is specificity. However, there are some situations in which the limitation to the test is not low specificity but rather low sensitivity.

Prosthetic joint infections: radionuclide state-of-the-art imaging.

Prosthetic joint replacement surgery is performed with increasing frequency. Overall the incidence of prosthetic joint infection (PJI) and subsequently prosthesis revision failure is estimated to be between 1 and 3%. Differentiating infection from aseptic mechanical loosening, which is the most common cause of prosthetic failure, is especially important because of different types of therapeutic management. Despite a thorough patient history, physical examination, multiple diagnostic tests and complex algorithms, differentiating PJI from aseptic loosening remains challenging. Among imaging modalities, radiographs are neither sensitive nor specific and cross-sectional imaging techniques, such as computed tomography and magnetic resonance imaging, are limited by hardware-induced artefacts. Radionuclide imaging reflects functional rather than anatomical changes and is not hampered by the presence of a metallic joint prosthesis. As a result scintigraphy is currently the modality of choice in the investigation of suspected PJI. Unfortunately, there is no true consensus about the gold standard technique since there are several drawbacks and limitations inherent to each modality. Bone scintigraphy (BS) is sensitive for identifying the failed joint replacement, but cannot differentiate between infection and aseptic loosening. Combined bone/gallium scintigraphy (BS/GS) offers modest improvement over BS alone for diagnosing PJI. However, due to a number of drawbacks, BS/GS has generally been superseded by other techniques but it still may have a role in neutropenic patients. Radiolabelled leucocyte scintigraphy remains the gold standard technique for diagnosing neutrophil-mediated processes. It seems to be that combined in vitro labelled leucocyte/bone marrow scintigraphy (LS/BMS), with an accuracy of about 90%, is currently the imaging modality of choice for diagnosing PJI. There are, however, significant limitations using in vitro labelled leucocytes and considerable effort has been devoted to developing alternative radiotracers, such as radiolabelled HIGs, liposomes, antigranulocyte antibodies and fragments, as well as more investigational tracers such as radiolabelled antibiotics, antimicrobial peptides, bacteriophages and thymidine kinase. On the other hand, positron emission tomography (PET) is still growing in the field of PJI imaging with radiotracers such as (18)F-fluorodeoxyglucose (FDG), (18)F-FDG white blood cells and (18)F-fluoride. But unfortunately this superb tomographic technique will only receive full acceptance when specific PET uptake patterns can be successfully developed. The emergence of hybrid modality imaging using integrated single photon emission computed tomography (SPECT) and PET with computed tomography (SPECT/CT and PET/CT) may also have a contributing role for more accurate assessment of joint replacement complications, especially combined with new radiotracers such as (68)Ga and (64)Cu. Finally, in searching for infection-specific tracers, currently there is no such diagnostic agent available.

Altered biodistribution and incidental findings on gallium and labeled leukocyte/bone marrow scans.

Gallium-67 citrate and labeled leukocyte imaging are established procedures for diagnosing inflammation and infection. Knowledge of the normal biodistribution of these tracers, variations, and unusual disease presentations improves the accuracy of their interpretation. During the first 24 hours after injection, the principal excretory pathway of gallium is renal; subsequently, excretion is primarily colonic. By 72 hours, approximately 75% remains in the body, equally distributed among soft tissues, liver, and bone/bone marrow. This normal distribution is subject to considerable variation. Nasopharyngeal and lacrimal gland uptake can be prominent. Breast uptake, generally faint and symmetric, is intense in hyperprolactinemic states such as pregnancy. Colonic uptake is very variable. Normally healing surgical incisions concentrate gallium for variable amounts of time. In patients receiving multiple transfusions renal, bladder, and bone activity are increased; liver and colon uptake are decreased. The contrast agent gadolinium exerts similar effects. At 24 hours after injection, the normal biodistribution of indium labeled leukocytes is limited to liver, spleen, and bone marrow. The normal biodistribution of technetium-labeled leukocytes includes, in addition to the reticuloendothelial system, colon, urinary tract, and occasionally gall bladder. Images obtained shortly after injection of labeled leukocytes show intense pulmonary activity, which decreases over time. Except in cystic fibrosis, segmental or lobar pulmonary activity indicates bacterial pneumonia. Diffuse pulmonary uptake is associated with various conditions but rarely with bacterial pneumonia. Labeled leukocytes do not accumulate in surgical wounds that heal by primary intention. They do accumulate in wounds healing by secondary intention, such as ostomies and skin grafts. Because labeled leukocytes accumulate in the bone marrow, complementary bone marrow imaging helps differentiate marrow activity from infection. Labeled leukocyte imaging is not useful for diagnosing spinal osteomyelitis because 50% or more of cases present as nonspecific decreased activity. This test is not useful for diagnosing septic arthritis because labeled leukocytes accumulate in inflammatory, noninfectious arthritis. Nodal uptake in patients with lower extremity joint prostheses produces incongruent white blood cell/marrow images in the absence of infection. Careful attention to uptake patterns minimizes this problem. Radiation effects on bone marrow activity are dramatic. Acutely, there is intense, diffusely increased activity. As inflammation subsides, and marrow becomes fibrotic, the irradiated area appears as decreased activity.

The evolution of nuclear medicine and the musculoskeletal system.

This article reviews the evolution of nuclear medicine in the evaluation of the musculoskeletal system over the past hundred years, from autoradiography and Geiger counters and rectilinear scanners to sophisticated imaging devices that provide both functional and morphological information. Initially synonymous with bone scanning, radionuclide evaluation of musculoskeletal disorders now includes gallium, labeled leukocytes, FDG, and fluourine-18, indications and applications of which are reviewed.

Nuclear medicine and diabetic foot infections.

Up to 25% of the diabetic population is at risk for developing a pedal ulcer. These ulcers serve as a portal of entry for osteomyelitis and overlie more than 90% of diabetic pedal osteomyelitis cases. The diagnosis of osteomyelitis often is overlooked, and imaging studies are an essential part of the evaluation. The most commonly performed radionuclide tests are bone and labeled leukocyte imaging. Focal hyperperfusion, focal hyperemia, and focal bony uptake on the 3-phase bone scan comprise the usual presentation of osteomyelitis. Many conditions to which the diabetic population with foot problems is prone, however, mimic osteomyelitis, and the test is sensitive but not specific. Consequently, the bone scan often is used as a screening test or to facilitate localization of activity on labeled leukocyte images. Because of its high sensitivity and prevalence of positive results, its value as a screening test is questionable. Investigations comparing labeled leukocyte imaging alone to labeled leukocyte plus bone imaging, demonstrate only marginal improvement for the combined study. Thus, it is time to reevaluate the role of the bone scan in diabetic foot infections. Labeled leukocyte imaging is the radionuclide procedure of choice for evaluating diabetic pedal osteomyelitis. Sensitivity and specificity range between 72% and 100%, and 67% and 98%, respectively. Although intraindividual comparisons are few, the accuracy of the test is similar, whether the leukocytes are labeled with (99m)Tc or (111)In. Labeled leukocytes accumulate in uninfected neuropathic joints, and marrow scintigraphy may be needed to determine whether infection is present. Alternatives to labeled leukocyte imaging include in vivo methods of labeling leukocytes, radiolabeled polyclonal IgG, and radiolabeled antibiotics. The results obtained have been variable and none of these agents is available in the United States. There are few data available on single-photon emission computed tomography/computed tomography. It probably will be useful in the mid and hind foot; in the distal forefoot, given the small size of the structures, its value is less certain. Data on (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography are limited and inconclusive, and further investigation is needed.

Nuclear medicine and the infected joint replacement.

Nearly 700,000 hip and knee arthroplasties are performed annually in the United States. Although the results in most cases are excellent, implants do fail. Complications like heterotopic ossification, fracture, and dislocation are now relatively rare and easily diagnosed. Differentiating aseptic loosening, the most common cause of prosthetic joint failure, from infection, is important because their treatments are very different. Unfortunately, differentiating between these 2 entities can be challenging. Clinical signs of infection often are absent. Increased peripheral blood leukocytes, erythrocyte sedimentation rate, and C-reactive protein levels are neither sensitive nor specific for infection. Joint aspiration with Gram stain and culture is the definitive diagnostic test. Its specificity is in excess of 90%; its sensitivity is variable, however, ranging from 28% to 92%. Plain radiographs are neither sensitive nor specific and cross-sectional imaging modalities, such as computed tomography and magnetic resonance imaging, can be limited by hardware-induced artifacts. Radionuclide imaging is not affected by orthopedic hardware and is the current imaging modality of choice for suspected joint replacement infection. Bone scintigraphy is sensitive for identifying the failed joint replacement, but cannot be used to determine the cause of failure. Neither periprosthetic uptake patterns nor performing the test as a 3-phase study significantly improve accuracy, which is only about 50-70%. Thus, bone scintigraphy typically is used as a screening test or in conjunction with other radionuclide studies. Combined bone gallium imaging, with an accuracy of 65-80%, offers only modest improvement over bone scintigraphy alone. Presently, combined leukocyte/marrow imaging, with approximately 90% accuracy, is the radionuclide imaging procedure of choice for diagnosing prosthetic joint infection. In vivo leukocyte labeling techniques have shown promise for diagnosing musculoskeletal infection; their role in prosthetic joint infection has not been established. (111)In-labeled polyclonal immunoglobulin lacks specificity. (99m)Tc-ciprofloaxicin does not consistently differentiate infection from aseptic inflammation. (18)F-fluorodeoxyglucose positron emission tomography has been extensively investigated; its value in the diagnosis of prosthetic joint infection is debatable.