Respective performance of 18F-FDG PET and radiolabeled leukocyte scintigraphy for the diagnosis of prosthetic valve endocarditis.

UNLABELLED: Echocardiography plays a key role in the diagnosis of infective endocarditis (IE) but can be inconclusive in patients in whom prosthetic valve endocarditis (PVE) is suspected. The incremental diagnostic value of (18)F-FDG PET and radiolabeled leukocyte scintigraphy in IE patients has already been reported. The aim of this study was to compare the respective performance of (18)F-FDG PET and leukocyte scintigraphy for the diagnosis of PVE in 39 patients. METHODS: (18)F-FDG PET and leukocyte scintigraphy were performed on 39 consecutive patients admitted because of clinically suspected PVE and inconclusive echocardiography results. The results of (18)F-FDG PET and leukocyte scintigraphy were analyzed separately and retrospectively by experienced physicians masked to the results of the other imaging technique and to patient outcome. The final Duke-Li IE classification was made after a 3-mo follow-up. RESULTS: Of the 39 patients, 14 were classified as having definite IE, 4 as having possible IE, and 21 as not having IE. The average interval between (18)F-FDG PET and leukocyte scintigraphy was 7 ± 7 d. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93%, 71%, 68%, 94%, and 80%, respectively, for (18)F-FDG PET and 64%, 100%, 100%, 81%, and 86%, respectively, for leukocyte scintigraphy. Discrepancies between the results of (18)F-FDG PET and leukocyte scintigraphy occurred in 12 patients (31%). In patients with definite IE, 5 had true-positive (18)F-FDG PET results but false-negative leukocyte scintigraphy results. Of these 5 patients, 3 had nonpyogenic microorganism IE (Coxiella or Candida). Of patients for whom endocarditis had been excluded, 6 had true-negative leukocyte scintigraphy results but false-positive (18)F-FDG PET results. These 6 patients had been imaged in the first 2 mo after the last cardiac surgery. The last patient with a discrepancy between (18)F-FDG PET and leukocyte scintigraphy was classified as having possible endocarditis and had positive (18)F-FDG PET results and negative leukocyte scintigraphy results. CONCLUSION: (18)F-FDG PET offers high sensitivity for the detection of active infection in patients with suspected PVE and inconclusive echocardiography results. Leukocyte scintigraphy offers a higher specificity, however, than (18)F-FDG PET for diagnosis of IE and should be considered in cases of inconclusive (18)F-FDG PET findings or in the first 2 mo after cardiac surgery.

Use of anti-granulocyte scintigraphy with 99mTc-labeled monoclonal antibodies for the diagnosis of periprosthetic infection in patients after total joint arthroplasty: a diagnostic meta-analysis.

The accurate diagnosis of periprosthetic joint infections (PJI) is crucial for therapy and the prevention of complications. No diagnostic test of PJI is 100% accurate. The aim of this study was to assess the use of anti-granulocyte scintigraphy using 99 mTc-labeled monoclonal antibodies to diagnose PJI after total joint arthroplasty. A systematic search of all relevant studies published through January 2013 was conducted using the MEDLINE, EMBASE, OVID, and ScienceDirect databases. Observational studies that assessed the accuracy of the anti-granulocyte scintigraphy with monoclonal antibodies or antibody fragments labeled with technetium 99 m in diagnosis for PJI and provided data on specificity and sensitivity were identified. Standard methods recommended for meta-analysis of diagnostic accuracy were used. Nineteen studies were eligible for inclusion. The results demonstrated that the area under the summary receiver operator curve was 0.88, and the diagnostic accuracy (Q*) was 0.81. Additionally, the diagnostic odds ratio (DOR) was 18.76 with a corresponding 95% confidence interval of 10.45-33.68. The pooled sensitivity and specificity of the diagnostic method for the diagnosis of PJI were 83% and 79%, respectively, while the pooled positive likelihood ratio (PLR) was 3.56, and the negative likelihood ratio (NLR) was 0.26. Anti-granulocyte scintigraphy using 99 mTc-labeled monoclonal antibodies has a reasonable role in the diagnosis of PJI after total joint arthroplasty. Due to the limitations of the present meta-analysis, additional high-quality original studies are required to confirm the predictive value.

Leucocyte scintigraphy with 111In-oxine for assessment of cell trafficking after extracorporeal photopheresis.

Extracorporeal photopheresis (ECP) is an established therapy for transplant rejection, graft-versus-host disease (GvHD) after allogeneic stem cell transplantation, cutaneous T-cell lymphoma and systemic autoimmune disorders such as systemic sclerosis. Knowledge regarding the in vivo behaviour of the cells after reinfusion is very limited. The aim of this prospective study was to investigate the path of 8-MOP-/UVA-exposed radiolabelled cells after ECP treatment and reinfusion. In this prospective single-centre study, peripheral blood mononuclear cells (PBMC) and neutrophils of 10 patients undergoing ECP as part of their regular treatment were labelled separately with (111) In-oxine after exposure to 8-MOP/UVA and prior to reinfusion. The fate of the labelled leucocytes was monitored at 10 min, 3.5 and 24 h following reinfusion with whole-body scintigraphy. Comparison of distribution patterns showed that PBMC and neutrophils have different kinetic patterns after intravenous reinjection. The most prominent difference was immediate retention of PBMC but not of neutrophils in the lungs corresponding to a signal three times more intense. After 24 h, more than 80% of both cell populations could be detected in liver and spleen. By means of a novel tool allowing for tracking of 8-MOP-/UVA-exposed leucocytes in ECP, we could show that organ-specific homing of leucocytes after ECP can be visualized in vivo and that migration patterns differ between PBMC and neutrophils. Based on our results, further studies should (i) extend the morphometric studies described here to specific ECP-responsive conditions and (ii) functionally address the interaction of ECP-modified PBMC with pulmonary tissue in experimental models.

[The influence of cardiopulmonary bypass operation on the biodistribution of 99mTc-HMPAO-labelled granulocytes - Evaluation in pigs by planar scintigraphy and section-analyses]. / Einfluss der extrakorporalen Perfusion auf die Biodistribution 99mTc-HMPAO-markierter Granulozyten. Evaluierung im Schwein mittels planarer Szintigraphie und Sektionsanalytik.

AIM: of the study was to evaluate the influence of an extra corporal perfusion (cardiopulmonary bypass operation - cpb) on activation and biodistribution of (99m)Tc labelled granulocytes in pigs with and without inhibition of the granulocytes by a leukocyte inhibition module (LIM). The cpb is often related to an activation of granulocytes resulting in an inflammatory answer. The biological mechanisms are unsolved yet. First trials of our group showed that LIM may inhibit the activation of neutrophils and therefore antagonize a cpb-caused impairment of cardiac function. This study is the continuation of these experiments with a higher number of animals and the focus on scintigraphic imaging. ANIMALS, MATERIAL, METHODS: 39 German landrace pigs were subdivided into three groups: group A (control) median sternotomy without cpb, group B with cpb, group C with LIM in addition to cpb. After labelling with (99m)Tc-HMPAO autologues granulocytes were reinjected. Subsequently to cpb, the animals underwent scintigraphic imaging. Quantification was performed with ROI evaluation and with tissue samples (section analysis) examined in a well counter. RESULTS: A high uptake of (99m)Tc-HMPAO was found in the liver. The count rates in brain, heart, lung, spleen and kidneys were far below. The amount of 99mTc-activity in the organ related to the half life corrected administered activity [%] was for the tissue samples (group A/B/C): brain 0.01/0.02/0.03; lung 12.1/8.3/11.5; heart 0.35/0.54/0.42; kidney 1.24/0.87/1.02; spleen 4.0/4.0/4.5, liver 16.8/20.9/19.6. The count rates determined by ROI-evaluation of the scintigraphic images related to the total count rate in the image [%] were (group A/B/C): brain 1.1/0.9/1.0; lung 15.6/10.4/12.2; heart 4.0/3.5/3.4; kidney 4.0/2.9/3.2; spleen 7.6/7.7/9.5, liver 23.1/36.7/31.4. A significant difference in the tracer uptake between the groups could neither be detected by scintigraphic imaging nor evaluation of tissue samples. CONCLUSION: Scintigraphic imaging as well as section analysis showed a comparable biodistribution of the tracer. Therefore, the initial results of our group were not confirmed with a considerably higher number of animals. Neither cpb nor the use of the LIM influenced distribution of 99mTc-labelled granulocytes in pigs significantly.

Is 99mTc-HMPAO granulocyte scan an alternative to endoscopy in pediatric chronic inflammatory bowel disease (IBD)?

Although endoscopy with biopsy is the gold standard for the diagnosis of inflammatory bowel disease (IBD), this procedure is invasive and its repetition is stressful, especially in children. The purpose of this study was to evaluate prospectively the role of (99m)Tc-HMPAO-labeled granulocyte scintigraphy in the diagnosis and follow-up of pediatric IBD and its possible use as an alternative to colonoscopy to determine the disease extent and severity beyond its ability to differentiate ulcerative colitis from Crohn's disease. During a 10-year period, 52 children, aging between 2 and 17 years (median, 11.09 years), were subjected to (99m)Tc-HMPAO granulocyte scan 7-28 days from conventional diagnostic tests, and the results were compared with endoscopic and bioptic results. Disease severity was graded by the focal uptake intensity versus iliac bone uptake (Scan Activity Index) and compared with Endoscopy Mayo Score. In 15 out of 16 patients, IBD diagnosis was obtained with a full correspondence of location and severity of lesions, respectively, in 14 out of 16 and 13 out of 16, while in 31 out of 36 patients, IBD was correctly excluded (sensitivity of 93.7%, specificity of 86.1%, and negative predictive value of 96.4%). During the follow-up, all relapses (24) and remissions (13) were correctly recognized (sensibility and specificity of 100%). In conclusion, (99m)Tc-HMPAO granulocyte scan is an accurate minimally invasive technique with very good accuracy, able to diagnose and to grade the intensity and extent of the disease; it is also a useful tool in the follow-up of pediatric IBD where it could reliably replace the invasive endoscopic assessment in most cases.

Targeting NCA-95 and other granulocyte antigens and receptors with radiolabeled monoclonal antibodies (Mabs).

During the last decade considerable effort has been made in the research for in vivo techniques of labeling neutrophils with peptides, labeled cytokines and (99m)Tc-labeled antigranulocyte monoclonal antibodies (AG-Mabs). In general the advantage of in vivo labeling is the simplicity of this approach compared with in vivo techniques. Three of these AG-Mabs have been evaluated in clinical studies: Besilesomab (Scintimun®), Sulesomab (Leucoscan®) and Fanolesomab (Leu-Tech®). White blood cells (WBCs) radiolabeled with AG-Mabs do not show the same behaviour as in vivo labeled white blood cells. Especially (99m)Tc-Sulesomab and (99m)Tc-Besilesomab image infectious foci mainly by non-specific extravasation with secondary binding to postmigratory leukocytes already present at the site of infection.

Clinical role of anti-granulocyte MoAb versus radiolabeled white blood cells.

Scintigraphy with white blood cells (WBC), labeled with ¹¹¹In-oxine or (99m)Tc-hexamethylpropyleneamine oxime (HMPAO), and anti-granulocyte scintigraphy using (99m)Tc-labeled monoclonal antibodies (MoAb), or fragments thereof, are established procedures for the diagnostic workup of infectious or inflammatory disease processes. Clinically severe afflictions such as fever of unknown origin (FUO), infectious joint replacements, osteomyelitis, vascular graft infections or cardiovascular infections often present where noninvasive proof of granulocytic inflammatory activity is more useful than mere morphology-based radiological diagnostic approaches. The labeling differences between WBC and antigranulocyte antibodies produce different pharmacokinetics and patterns of tracer accumulation and distribution. Together with the physical imaging properties of the respective isotope used for imaging, the diagnostic value of a tracer depends on the clinical setting. Thus, despite the easier and safer handling of antibody-based in-vivo labeling, indications for in-vivo labeled WBC remain. As a consequence there is as yet no ideal inflammation tracer, also bearing in mind that neither WBCs nor antibody-diagnostics can reliably differentiate sterile inflammation from infection. Although positron emission tomography (PET) using e.g. FDG-PET is replacing conventional scintigraphies in some indications, both in vivo and in vitro labelled leukocytes will remain an important clinical pillar in the diagnosis of infection and inflammation.

Diagnosing prosthetic vascular graft infection with the antigranulocyte antibody 99mTc-fanolesomab.

AIM: The objectives of this retrospective investigation were to determine the accuracy of 99mTc-fanolesomab, an antigranulocyte antibody, for diagnosing prosthetic vascular graft infection, ascertain optimum imaging times for this indication, and assess safety of this agent. METHODS: Eighteen patients with 19 prosthetic vascular grafts were included. Indications for graft placement included peripheral vascular disease (8), haemodialysis (7), and aneurysm (4). Patients were imaged 2-5 h and 18-30 h after injection of 555-740 MBq (75-125 microg) 99mTc-fanolesomab. One experienced nuclear physician reviewed images in three separate sessions, early alone, late alone and early plus late images together. When early and late images were read alone, graft activity more intense than native blood pool activity was classified as positive for infection. When early and late images were interpreted together, graft activity which persisted or which increased in intensity over time was classified as positive for infection. Patient records were reviewed for adverse events up to 30 days after injection. RESULTS: Five (26%) prosthetic grafts were infected. Early, late and early plus late imaging were equally sensitive (1.00). Early images were significantly less specific (0.50), than late and early plus late images (0.93) (P<0.05, analysis of proportions). Accuracy of late imaging and early plus late imaging were the same: 0.93. No patient experienced adverse events following radiopharmaceutical injection. CONCLUSIONS: 99mTc-fanolesomab imaging, performed 18-30 h after injection, diagnosed prosthetic vascular graft infection safely and accurately (95%). (Although safety was not an issue in this investigation, following reports of serious, including two fatal, events after administration, 99mTc-fanolesomab was withdrawn from the United States market).

[Status and perspectives of non invasive cell tracking]. / Status und Zukunft des nichtinvasiven Zell-Trackings.

The interaction of different cells is an important regulator in the development of many diseases, including cancer. Some cells are recruited directly from the local tissue environment, others reach the pathological focus via the circulation. Using non-invasive cell tracking methods, the distribution and migration of labeled cells can be studied in experimental animal models, and the role of these cells on the pathogenesis of disease can thus be elucidated. Scintigraphy and SPECT, and especially MRI and optical imaging, are frequently used for this purpose. Studies are mostly performed with macrophages and granulocytes (inflammatory cells), which accumulate in nephritis, encephalitis, and tumors. At present, the understanding of progenitor cell migration and differentiation is gaining increasing interest in neurological disorders (for example Parkinson's disease) and in cardiac diseases (for example myocardial infarction). Non-invasive cell tracking is already established in basic research; in the future, a clinical application of cell tracking is foreseeable in the framework of cell therapy.

MRI versus scintigraphy with 99mTc-HMPAO-labelled granulocytes in the diagnosis of bone infection.

PURPOSE: To assess the reliability of MRI and scintigraphy with 99mTc-HMPAO-labelled granulocytes in the diagnosis of bone infection. MATERIALS AND METHODS: Between November 2001 and November 2003, 25 patients (16 men and 9 women; age range 22-72 years; mean age 48 years) with suspected bone infection were evaluated. The lower limbs were more frequently involved (20/25 cases). MRI (T1 and T2-w sequences, both with and without fat suppression; T1-w fat-suppressed sequence after Gadolinium administration) and scintigraphy with 99mTc-HMPAO-labelled granulocytes were performed in all patients; the study was performed 30 min, 150 min and 24 h after the injection of 99mTc labelled autologous granulocytes. The maximum interval between MRI and scintigraphy was 15 days. The diagnosis was confirmed surgically (18/25 cases) or by clinical follow-up (7/25 cases). RESULTS: In 10/25 cases the clinical suspicion of bone infection was confirmed by MRI, scintigraphy and surgery. In 12/25 cases the clinical suspicion of bone infection was not confirmed either by imaging, surgery (5/12 cases) or follow-up (7/12 cases). In 3/25 cases the results were discordant: in 1/3 cases with chronic osteomyelitis confirmed by MRI and surgery, a false-negative diagnosis was made by scintigraphy. In 2/3 cases with negative MRI diagnoses confirmed by surgery, a false-positive diagnosis was made by scintigraphy owing to the infection of adjacent soft tissues. CONCLUSIONS: MRI is more reliable for the detection and evaluation of the local spread of bone infection. Conversely, when metallic devices causing artefacts on MR images are present, scintigraphy is the preferred alternative modality.

Scintigraphic imaging of infectious foci with an 111In-LTB4 antagonist is based on in vivo labeling of granulocytes.

UNLABELLED: Radiolabeled leukotriene B4 (LTB4) antagonist DPC11870 is able to reveal infectious and inflammatory foci in distinct animal models. Because previous studies showed that accumulation of (111)In-DPC11870 in the abscess continued although the tracer had cleared from the circulation, we decided to investigate the pharmacodynamics of (111)In-DPC11870 and determine the mechanism of accumulation of the radiolabeled LTB4 antagonist in the abscess. METHODS: (111)In-DPC11870 was intravenously injected in healthy New Zealand White rabbits and rabbits with intramuscular Escherichia coli infection. Pharmacodynamics were studied by serial imaging and by ex vivo counting of dissected tissues. The mechanism of visualization of the abscess was investigated in rabbits with intramuscular infection that was induced 16 h after intravenous administration of (111)In-DPC11870. In addition, heterologous leukocytes and bone marrow cells of a donor rabbit were labeled with (111)In-DPC11870 in vitro and the biodistribution of these in vitro radiolabeled cells was compared with that of (111)In-DPC11870 in rabbits with an infection. RESULTS: The LTB4 antagonist (111)In-DPC11870 revealed the intramuscular abscess in rabbits only a few hours after injection. Quantitative analysis of the images confirmed accumulation of (111)In-DPC11870 in the abscess although the compound had cleared almost completely from the circulation. Radioactivity concentration in the bone marrow decreased more rapidly in infected animals than in healthy animals. Therefore, we hypothesized that (111)In-DPC11870 associates with receptor-positive (bone marrow) cells and accumulated in the abscess because of subsequent migration from the bone marrow to the abscess. Accumulation of radioactivity in the abscess induced 16 h after (111)In-DPC11870 injection was similar to that in animals intravenously injected with the tracer 24 h after induction of the abscess (0.37 +/- 0.16 percentage injected dose [%ID]/g). Moreover, differences in radioactivity concentration in the bone marrow of healthy and infected animals (0.67 +/- 0.29 %ID/g and 0.15 +/- 0.03 %ID/g at 24 h, respectively, after injection) supported our hypothesis. Additional studies with peripheral blood leukocytes and bone marrow cells that were labeled ex vivo with (111)In-DPC11870 showed the ability of these cells to migrate to the abscess (0.40 %ID/g and 0.52 %ID/g for (111)In-DPC11870 bone marrow cells and (111)In-DPC11870 peripheral blood leukocytes, respectively, 24 h after injection). CONCLUSION: The (111)In-labeled LTB4 antagonist DPC11870 accumulates in infectious and inflammatory foci because of binding to LTB4 receptors expressed on activated hematopoietic cells that subsequently migrate to the site of infection, which leads to visualization of the infectious lesions.

Noninvasive diagnosis of small bowel Crohn's disease: combined use of bowel sonography and Tc-99m-HMPAO leukocyte scintigraphy.

BACKGROUND: Crohn's disease (CD) is frequently localized in the small bowel, with the diagnosis of disease and the assessment of its extension made by ileo-colonoscopy (IC) and small bowel enteroclysis (SBE). Transabdominal bowel sonography (BS) and Tc-99m-HMPAO leukocyte scintigraphy (LS) are increasingly used for the diagnosis of CD because of their minimal invasiveness, reproducibility, and acceptable costs. METHODS: From March 2000 to July 2003, we performed IC, SBE, BS, and LS in 84 patients with either suspected or known small bowel CD. RESULTS: Small bowel CD was present in 50 patients, whereas the other 34 patients received a different diagnosis. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were, respectively, 98%, 97%, 98%, 97%, and 0.97 for SBE; 92%, 97%, 98%, 88%, and 0.94 for BS; and 90%, 93%, 96%, 85%, and 0.92 for LS. In addition, the combined use of BS and LS led to overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 100%, 93%, 96%, 100%, and 0.97, respectively. BS showed a fair concordance with SBE in terms of location (k = 0.71) and a correlation with the extension of the disease (r = 0.67, P < 0.001). LS showed a concordance with SBE with regard to location in about one-half the population (k = 0.54), whereas it was less effective than SBE in defining disease extension. CONCLUSIONS: BS and LS are 2 accurate techniques for the diagnosis of small bowel CD, and their combined use can be recommended as an early diagnostic approach to patients in which the disease is suspected. SBE remains the best procedure for the definition of the location and extension of the disease.

Quantification of disease activity in patients undergoing leucocyte scintigraphy for suspected inflammatory bowel disease.

PURPOSE: Whole-body gamma camera counting is an alternative to faecal 111In collection for quantifying disease activity in inflammatory bowel disease (IBD) but requires administration of imaging activities of 111In. The aim of this study was to explore a dedicated whole-body counter which requires 20-fold less activity than gamma camera counting. METHODS: Thirty patients with known or suspected IBD received 99mTc-granulocytes (approximately 200 MBq) and 111In-granulocytes (approximately 0.5 MBq). The 99mTc-cells were injected 45 min after the 111In-cells and immediately after a baseline 111In whole-body count. The decay-corrected count at 120 h was expressed as a fraction of baseline to give whole-body 111In retention (WBR). One patient was excluded as the injected cells were non-viable. RESULTS: Median 45-min intravascular 111In recovery was 35% in patients compared with 43% in six normal volunteers (p<0.05). WBR in normals ranged from 91% to 93% and in 11 patients with negative 99mTc imaging from 87% to 96%. Only one of 11 patients with negative imaging had WBR <90% while 11/12 patients with WBR <90% had abnormal imaging. Ten of 13 patients with Crohn's disease (CD) had abnormal imaging. The lowest WBR in these ten was 77% and six had values of >90%. There was a significant association between WBR and 99mTc image grade (Rs=0.73, p<0.002) in 16 patients without CD, but not in 13 patients with CD (Rs=0.54, p>0.05). CONCLUSION: Dedicated whole-body counting is able to quantify disease activity in IBD but may give normal values in active CD.

Bone infection in patients suspected of complicating osteomyelitis: the diagnostic value of dual isotope bone-granulocyte scintigraphy.

AIM: The purpose of this study was to evaluate the diagnostic value of dual isotope bone-granulocyte scintigraphy in patients with known bone pathology clinically suspected of osteomyelitis, i.e. complicating osteomyelitis, using per-operative bacterial culture from bone as reference. METHODS: Simultaneous dual isotope bone-granulocyte scintigraphic images were obtained in 42 consecutive patients in whom conventional X-ray, erythrocyte sedimentation rate, and C-reactive protein were also available. 99mTc MDP bone and 111In labelled granulocyte imaging was obtained simultaneously. The images were interpreted as positive for osteomyelitis if regions of interests of pathologic 111In granulocyte accumulation included 99mTc MDP activity on the bone images (except in the spine). RESULTS: The sensitivity, specificity, and accuracy were 84, 71 and 79%, respectively, for simultaneous, dual isotope bone-granulocyte scintigraphy, higher than the other diagnostic parameters. CONCLUSION: Simultaneous bone-granulocyte scintigraphy is a valuable diagnostic tool in diagnosing osteomyelitis complicating other bone pathology with or without soft-tissue infection.

Diagnosing suspected acute nonclassic appendicitis with sulesomab, a radiolabeled antigranulocyte antibody imaging agent.

PURPOSE: The aim of this study was to investigate the potential role of a technetium 99m-labeled antigranulocyte murine antibody Fab' fragment (sulesomab) as a diagnostic imaging agent in children with suspected acute nonclassic appendicitis. METHODS: Serial planar images at 15 to 30 minutes, 1, 2, and 4 hours and single-photon emission computed tomography (SPECT) images were acquired after sulesomab injection. In 40 children with suspected acute nonclassic appendicitis, imaging results were confirmed surgically in 21 patients, whereas 19 nonsurgical patients resolved presenting signs and symptoms and were considered to not have appendicitis. RESULTS: Sulesomab imaging had 95% sensitivity, 90% specificity, 95% negative predictive value, and 90% positive predictive value for acute appendicitis. In 78% of patients, sulesomab accurately detected or excluded acute appendicitis and would have changed management plans. No patients had adverse events, and no human antimurine antibody response occurred in 18 evaluable patients. CONCLUSIONS: Sulesomab was well tolerated with no side effects and with no apparent immunogencity. Appendicitis was rapidly and accurately detected. In pediatric patients with suspected nonclassic appendicitis, management decisions incorporating sulesomab imaging provided benefit in separating surgical from nonsurgical patients.

Imaging of experimental colitis with a radiolabeled leukotriene B4 antagonist.

UNLABELLED: The use of radiolabeled leukocytes is considered the gold standard for scintigraphic imaging of inflammatory bowel disease. The disadvantages of (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)-leukocytes, however, encourage the search for new imaging agents with at least similar diagnostic accuracy but without the laborious preparation and subsequent risk of contamination. In this study we investigated the imaging characteristics of a new imaging agent that specifically binds to the leukotriene B(4) (LTB(4)) receptors expressed on neutrophils. Imaging characteristics of the (111)In-labeled LTB(4) antagonist (DPC11870) were compared with those of (18)F-FDG and (99m)Tc-HMPAO-granulocytes in a rabbit model of experimental colitis. METHODS: Acute colitis was induced in New Zealand White (NZW) rabbits by infusion of trinitrobenzene sulfonic acid in the descending colon. Forty-eight hours after induction of colitis, all animals were injected intravenously with (99m)Tc-granulocytes, (18)F-FDG, or (111)In-DPC11870. The pharmacokinetics and biodistribution were studied by serial scintigraphic imaging and by ex vivo counting of dissected tissues. RESULTS: All 3 radiopharmaceuticals showed the inflamed colon as early as 1 h after injection. However, compared with (99m)Tc-granulocytes, both (111)In-DPC11870 and (18)F-FDG were superior in revealing the inflamed lesions. The biodistribution data showed that uptake of (111)In-DPC11870 in the inflamed colon was highest (0.72 +/- 0.18 percentage injected dose per gram [%ID/g]), followed by uptake of (99m)Tc-granulocytes (0.40 +/- 0.11 %ID/g) and of (18)F-FDG (0.16 +/- 0.04 %ID/g). Because of low activity concentrations in the noninflamed colon, the radiolabeled LTB(4) antagonist also revealed the highest ratio of affected colon to unaffected colon (11.6 for (111)In-DPC11870, 5.5 for (99m)Tc-granulocytes, and 4.1 for (18)F-FDG). CONCLUSION: The radiolabeled LTB(4) antagonist DPC11870 clearly delineated acute colitis lesions in NZW rabbits within 1 h after injection. Because of high uptake in the inflamed lesions and a low activity concentration in the noninflamed colon, images acquired with (111)In-DPC11870 were better than those acquired with (99m)Tc-granulocytes or (18)F-FDG.

Fever of unknown origin: prospective comparison of diagnostic value of 18F-FDG PET and 111In-granulocyte scintigraphy.

The diagnostic work-up in patients with fever of unknown origin (FUO) is often challenging and frequently includes nuclear medicine procedures. Whereas a role for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a possible role of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in these patients remains to be established. To study this, we compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients with FUO underwent both FDG-PET and (111)In-granulocyte scintigraphy within 1 week. FDG-PET scans and granulocyte scintigrams were reviewed by different doctors who were blinded to the result of the other investigation. The diagnostic values of FDG-PET and granulocyte scintigraphy were evaluated with regard to identification of a focal infectious/inflammatory or malignant cause of FUO. The sensitivity of granulocyte scintigraphy and FDG-PET were 71% [95% confidence interval (CI): 37-85%] and 50% (CI: 16-84%), respectively. The specificity of granulocyte scintigraphy was 92% (71-100%), which was significantly higher than that of FDG-PET, at 46% (34-62%). Positive and negative predictive values for granulocyte scintigraphy were both 85%. Positive and negative predictive values for FDG-PET were 30% and 67%, respectively. (111)In-granulocyte scintigraphy has a superior diagnostic performance compared to FDG-PET for detection of a localised infectious/inflammatory or neoplastic cause of FUO. The poorer performance of FDG-PET is in particular attributable to a high percentage of false positive scans, leading to low specificity.