Granulocyte-specific monoclonal antibody technetium-99m-BW 250/183 and indium-111 oxine-labelled leucocyte scintigraphy in inflammatory bowel disease

Thirty-three patients suspected of suffering from inflammatory bowel disease were studied. Autologous leucocytes were labelled with indium 111 oxine and re-injected simultaneously with 0.3–0.5 mg of technetium 99m granulocyte-specific monoclonal antibody BW 250/183. Two scans were obtained, the early scan 3–4 h postinjection (p.i.) and the late scan 18–24 h p.i. Using the endoscopy study as standard, the diagnostic accuracy of both agents was determined. Sensitivity, specificity and accuracy of ¹¹¹In scans was 88.8%, 100.0% and 93.7% at 4 h and 94.7%, 100.0% and 96.9% at 24 h, respectively. Concerning the results using antibodies, the values were 61.1%, 100.0% and 78.1% at 4 h and 78.9%, 92.8% and 84.8% at 24 h, respectively. Segmental analysis showed concordance in 89.3% and 93.3% of the cases at 4 and 24 h, respectively. Though less sensitive and less accurate than scanning employing indium 111 leucocytes, BW 250/183 granulocyte-specific scintigraphy can be used for inflammatory bowel disease diagnosis and localization. Offprint requests to: J. Martin-Comin     

99Tcm and 111In leucocyte scintigraphy in inflammatory bowel disease.

A comparative study of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and 111In leucocyte scintigraphy was performed in inflammatory bowel disease. Two hundred and thirty-four patients were studied, 146 had 99Tcm-HMPAO, 82 had 111In and six had both. The sensitivity, specificity and accuracy of the 99Tcm leucocyte scan were 96, 97 and 97%, respectively, and 96, 97 and 97%, respectively, for the 111In leucocyte scan. 99Tcm-HMPAO leucocytes demonstrated similar diagnostic accuracy to 111In-labelled leucocytes with improved image quality and reduced radiation dose.     

Immunoscintigraphy of inflammatory processes with a technetium-99m-labeled monoclonal antigranulocyte antibody (MAb BW 250/183)

Antigranulocyte immunoscintigraphy with a technetium-99m- (99mTc) labeled monoclonal antigranulocyte antibody (MAb BW 250/183) was performed in 34 in-patients of the departments of accident surgery and internal medicine in order to prove or exclude inflammatory processes. After labeling with 99mTc, 555 MBq, 99mTc-MAb (0.5 mg antibody) were slowly injected intravenously over a period of 5 min. A whole-body scan was done 4-6 hr postinjection, and planar or SPECT images were performed 6, 18, and 24 hr postinjection. Leukocyte immunoscintigraphy proved inflammatory suppurating processes in 20 cases (true-positive) and excluded them in 11 cases (true-negative). The findings were false-positive in two patients (hematoma without signs of infection, pseudoarthrosis) and false-negative in one patient (encapsulated lung abscess with pleural fibrosis). Anti-idiotypic human anti-mouse antibodies (HAMA) were found only in one out of 20 patients. According to our experiences, immunoscintigraphy with 99mTc-MAb BW 250/183 has a sensitivity of 95%, and is, therefore, well suited for the identification of leukocytic inflammations.     

Image quality and radiopharmaceutical parameters of indium-111 granulocytes in scintigraphy of inflammatory bowel disease

This study was undertaken to investigate the influence of various parameters of injected autologous 111In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of 111In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq 111In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.     

Evaluation of white cell scintigraphy using indium-111 and technetium-99m labelled leucocytes

Indium-111 oxine labelled leucocyte (¹¹¹In oxine leucocyte) scintigraphy is the test of choice in detecting occult infection and localising focal inflammation. ¹¹¹In oxine labelling is technically difficult and expensive and leucocyte labelling with technetium-99m stannous colloid (^99mTc Sn colloid) has been considered to be an alternative. Leucocytes from 40 cases referred for investigation of occult infection or localisation of inflammation were simultaneously labelled with ¹¹¹In oxine and ^99mTc Sn colloid with dual isotope acquisition performed at 1, 3 and 24 h. Twenty-four hour ^99mTc Sn colloid scans were corrected for ¹¹¹In downscatter. Each case was independently interpreted by two experienced observers. Twentyone patients demonstrated positive ¹¹¹In oxine leucocyte scans. Using ¹¹¹In oxine leucocyte scans as the gold standard, ^99mTc Sn colloid leucocyte scanning had an overall sensitivity of 86% and a specificity of 95%. Clinical follow-up verified that three patients had false negative ^99mTc Sn colloid leucocyte scans and one patient had a false positive. Further clinical evaluation of ^99mTc Sn colloid labelled leucocytes is required before they can become a reliable replacement for ¹¹¹In oxine leucocytes. Correspondence to: S. Boyd     

Radionuclide diagnosis of vertebral osteomyelitis: indium-111-leukocyte and technetium-99m-methylene diphosphonate bone scintigraphy

Seventy-six 111In-labeled leukocyte images performed on 71 patients with possible vertebral osteomyelitis were reviewed. Twenty-eight cases of vertebral osteomyelitis were diagnosed. Vertebral labeled leukocyte activity was normal in 2, increased in 11, and decreased in 15 cases of osteomyelitis. The median duration of symptoms was significantly longer in patients with osteomyelitis and decreased vertebral activity than in patients with osteomyelitis and increased activity (3 mo versus 2 wk; p = 0.019). No significant relationship between the duration of antibiotic therapy and the appearance of vertebral osteomyelitis on leukocyte images was identified (p = 0.62). Increased vertebral activity was highly specific (98%) for osteomyelitis but relatively insensitive (39%). Decreased activity was neither sensitive (54%) nor specific (52%). Seven patients with clinically resolved infection underwent follow-up imaging. Of four patients who initially presented with increased activity, one had normal and three had decreased vertebral activity on follow up studies. All three patients with decreased activity initially had decreased activity on follow-up. Using increased or decreased activity as criteria for infection, the accuracy of leukocyte imaging for diagnosing vertebral osteomyelitis was 66%, similar to that of 99mTc bone imaging (63%) in our population. Leukocyte imaging did however provide important information about extraosseous infection in 12 of the patients studied.     

The role of indium-111 white blood cells in inflammatory bowel disease

Inflammatory bowel disease in patients may be difficult to diagnose because of the complex problems associated with this disease. Radionuclides are able to provide a rapid and effective method of imaging the bowel in patients with active inflammatory bowel disease. In the past, clinical work-ups have included barium x-ray studies and endoscopy. Scarring and fistula formation have made it difficult to determine between the active disease and abscesses that may occur. Gallium-67 (67Ga) has been very useful in imaging patients with inflammatory bowel disease, but the multiple-day imaging procedure has been a limitation for the clinicians when achieving a diagnosis. Recent results with Indium-111 (111In)--labeled WBCs have provided excellent correlation between clinical symptoms and colonoscopy findings in patients with inflammatory bowel disease. This technique has also allowed the differentiation between reoccurring inflammatory bowel disease and abscesses that accompany the disease within a 24-hour time period. The use of intravenous (IV) glucagon has increased the clarity of the images in the small bowel. Technetium 99m (99mTc) diethylenetriaminepentaacetic acid (DTPA) has been used in patients with inflammatory bowel disease demonstrating promising results. Investigators feel labelling 99mTc with WBCs will be improved, therefore yielding a greater efficiency, which will have a major impact on imaging patients with inflammatory bowel disease. Imaging patients with inflammatory bowel disease using radionuclides has yielded promising results. This is a significant advancement over barium radiography and endoscopy exams.     

99mTc-stannous colloid white cell scintigraphy in childhood inflammatory bowel disease.

99mTc-Labeled white cell scintigraphy (WCS) has been used for the investigation of inflammatory bowel disease (IBD) in adults, but data on children are limited. The most common agent used is (99m) Tc-hexamethylpropyleneamine oxime (HMPAO); however, this agent has limitations. In a retrospective study, we assessed the use of (99m)Tc-stannous colloid WCS for the initial evaluation of children with suspected IBD. METHODS: Diagnostic, endoscopic, and contrast radiography results were retrospectively collected from the medical records. Two experienced nuclear physicians unaware of the patient data interpreted the WCS results, with agreement reached by consensus. Statistical analysis was performed on the ability of WCS to detect active disease and localize it topographically and on a comparison of diagnostic methods, using a combination of clinical features and endoscopy as the reference standard. RESULTS: Between 1996 and 1999, 64 patients (35 male and 29 female; mean age, 12.5 y; age range, 2-19 y) had WCS performed, with IBD subsequently diagnosed in 34 patients. (99m)Tc-Stannous colloid WCS had an 88% sensitivity, 90% specificity, and 8.8 likelihood ratio for initial investigation of IBD. Agreement was poor for topographic localization of disease. Small-bowel series had a 75% sensitivity, 50% specificity, and 1.5 likelihood ratio for detecting endoscopic disease of the terminal ileum and proximal colon. CONCLUSION: Our results confirm that WCS is a useful imaging technique for the initial evaluation of patients with suspected IBD. (99m)Tc-Stannous colloid had results at least comparable to those of other WCS agents, and in children, (99m)Tc-stannous colloid WCS should be preferred in view of lower cost, shorter preparation time, and the smaller blood volumes required.     

99mTc-HMPAO labelled leucocyte scintigraphy in the diagnosis of pelvic inflammatory disease

BACKGROUND: Scintigraphy using leucocytes labelled with 99mTc hexamethylpropyleneamine oxime (99mTc-HMPAO) is widely used for the localization of inflammatory foci and abscesses in cases of acute pelvic inflammatory disease, which is one of the serious health problems of women of child-bearing age. Early diagnosis and effective management of this condition can preserve fertility and prevent serious complications, such as peritonitis and sepsis. AIM: To evaluate the importance of scintigraphy using 99mTc-HMPAO labelled leucocytes in the early diagnosis of patients with pelvic inflammatory disease. METHODS: Fifteen women (mean age 29.2+/-8 years, range 25-46 years) with suspicion of pyogenic pelvic inflammatory disease based on gynaecological examinations, clinical findings and blood tests were included in this study. The patients received 555 MBq 99mTc-HMPAO labelled leucocytes, by injection, and were scanned by scintigraphy 0.5-1, 3 and 24 h later in the anterior abdominal projection. Ten of the patients were then evaluated by abdominal or transvaginal ultrasonography, four by computed tomography and two by both ultrasound and computed tomography. The final diagnosis was made by surgical intervention. RESULTS: Scintigraphy detected pelvic inflammatory disease in five of the patients. In three of them the disease was apparent on the scans taken at 0.5-1 h, and in the other two it was apparent at 3 h. There were no false negative results, and one false positive result. The scan accurately reflected the absence of pelvic inflammatory disease in nine patients showing non-pathological tracer uptake in the lower abdominal region. CONCLUSION: We showed that scintigraphy with 99mTc-HMPAO labelled leucocytes had a sensitivity of 100%, specificity of 90%, overall accuracy of 93%, positive predictive value of 83%, and negative predictive value of 100%. Therefore, we conclude that 99mTc-HMPAO labelled leucocyte scans provide a rapid and highly accurate method for diagnosing pelvic inflammatory disease in women of child-bearing age. This adds an important contribution to the diagnosis of infection and helps determine further operative or conservative treatment.     

Quantification of pulmonary uptake of indium-111 labelled granulocytes in inflammatory bowel disease

This study describes a method for quantifying the pulmonary trapping of indium-111 labelled polymorphonuclear (PMN) cells in patients with inflammatory bowel disease (1131) in comparison to non-inflamed controls. Twenty patients with extensive IBD were studied by ¹¹¹In-PMN scintigraphy. Gamma-camera images were obtained at 2.5–4 h (early) and 20–25 h (late) after the injection of autologous PMNs labelled in plasma with ¹¹¹In-tropolonate. Local uptake in the chest, iliac bone marrow, spleen and liver was quantified as the counts per pixel per second per MBq of injected ¹¹¹In for both early and late scans. Fourteen subjects without inflammatory disease were studied as controls. IBD patients showed significantly greater loss of splenic activity between early and late scans compared with controls (mean ± SD: –35.7% ± 16.6% versus –4.5% ± 6.1%, P < 0.001). There was no significant difference between control and IBD groups with respect to liver and bone marrow uptake on both early and late scans. Chest uptake was significantly higher in patients with 11313 on both early (6.4 ± 1.6 cps/MBq/pix) and late (5.6 ± 1.5cps/MBq/pix) scans, compared with the controls (4.8 ± 1.3 cps/MBq/pix, P < 0.005 and 3.4 ± 1.0 cps/MBq/pix, P < 0.001 respectively). The chest uptake in the control group on the late scans demonstrated a significant linear correlation with iliac uptake (y=0.23x + 0.41, r=0.87, n=14). Assuming in controls that there is no parenchymal uptake of ¹¹¹In, this regression enables an estimate to be made, based on iliac counts, of the count rate from bone marrow in the chest wall. After subtraction of this from the total chest count rate, the true parenchymal uptake was derived, which averaged (2.86 ± 0.91) cps/MBq/pix in the IBD group compared to zero assumed in the control group. The higher lung ¹¹¹In-PMN uptake on the early scans in IBD compared to controls is suggested to reflect a combination of increased margination, compared to controls, and early migration, whilst the excess ¹¹¹In-PMN retention on late scans represents extravascular migration only. The bone marrow correction technique for quantification of pulmonary migration of ¹¹¹In-PMNs should prove useful for the evaluation of PMN kinetics in disease. Correspondence to: A.M. Peters     

Tc-99m MDP and indium-111 chloride scintigraphy in skeletal tuberculosis

A case of diffuse osseous tuberculosis with changes on skeletal Tc-99m methylene diphosphonate (MDP) and indium-111 chloride scintigraphy is presented. Only two other cases of bone scan findings in osseous tuberculosis (TB) were reported in the literature and both show patterns similar to diffuse metastatic disease. In addition, the demonstration of corresponding areas of decreased tracer activity on indium-111 bone marrow scintigraphy is a finding that has not been previously reported for skeletal tuberculosis.     

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 (200 MBq) and ¹¹¹In-granulocytes (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 Crohns 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 (R_s=0.73, p<0.002) in 16 patients without CD, but not in 13 patients with CD (R_s=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.     

Myocardial distribution of indium-111-antimyosin Fab and technetium-99m-sestamibi in experimental nontransmural infarction.

Early revascularization in acute myocardial infarction results in normal, necrotic and partially damaged and partially salvaged ("intermediate") myocardium. By combining a perfusion tracer and a marker for myocardial injury, we attempted to differentiate between these three types of cardiac tissue. The LAD was occluded in nine pigs for 45 min and then reperfused. After 48 and 72 hr, 74 MBq 111In-antimyosin Fab and 740 MBq 99mTc-sestamibi, respectively, were injected intravenously. Normally perfused myocardium was labeled with fluorescein and the heart excised. Three to four slices were cut from the apex. Tetrazolium staining revealed the zone of necrosis. Tracer distribution on double-nuclide scintigrams of the slices also reflected the three different myocardial zones. Guided by fluorescence and macrohistochemistry, tissue samples were excised from each zone. In relation to normal myocardium, mean activity in the intermediate zone was 0.82 +/- 0.20 for 99mTc-sestamibi and 2.84 +/- 1.31 for 111In-antimyosin Fab. Activity in necrotic myocardium was 0.30 +/- 0.19 and 3.95 +/- 2.47, respectively. These results show that 111In-antimyosin Fab fragments not only accumulate in necrotic but also in intermediate myocardium. Therefore, an overestimation of infarct size may occur if 111In-antimyosin Fab fragments are used alone without a perfusion tracer.     

Myocardial damage delineated by indium-111 antimyosin Fab and technetium-99m pyrophosphate

Technetium-99m-labeled pyrophosphate and radiolabeled antimyosin antibodies are two infarct localizing agents with apparently different kinetics of localization. To determine whether these agents localize in a similar fashion in early acute myocardial necrosis, we studied the simultaneous distribution of 111In-labeled antimyosin and 99mTc-labeled pyrophosphate in dogs after intracoronary (i.c.) (n = 9) or intravenous (i.v.) (n = 9) administration of a mixture of these two agents in a reperfused infarct model. The mean infarct size (+/- s.d.) delineated by pyrophosphate [20.2 +/- 14.1 (i.v.), 29.8 +/- 12.3 (i.c.)] was larger than that by antimyosin [14.2 +/- 11.3 (i.v.) (p = 0.05), 20.0 +/- 11.8 (i.c.) (p = 0.05)] which was larger than that by triphenyl tetrazolium chloride [13.9 +/- 8.0 (i.v.) (p = 0.05), 15.3 +/- 6.5 (i.c.) (p = 0.05)]. This overestimation persisted whether the radiopharmaceuticals were administered by intracoronary or intravenous injections, although the latter with antimyosin was only slightly larger (TTC:AM = 13.9:14.2) (p = n.s.). There was a good correlation, however, between antimyosin and pyrophosphate delineated infarct sizes in dogs with intracoronary injection (y = 0.82x + 13.33, r = 0.79) or i.v. injection (y = 1.208x + 3.01, r = 0.97) of the mixture of the two agents. Since the images of the 111In and 99mTc activities were obtained consecutively by identical methods, the overestimation of infarct size by pyrophosphate cannot be due to differences in spatial resolution of the techniques used. The differences in the areas of myocardial damage delineated by pyrophosphate and antimyosin in our study most probably denote the area of viable but compromised myocardium.     

Detection of occult infection following total joint arthroplasty using sequential technetium-99m HDP bone scintigraphy and indium-111 WBC imaging

Preoperative exclusion or confirmation of periprosthetic infection is essential for correct surgical management of patients with suspected infected joint prostheses. The sensitivity and specificity of [111In]WBC imaging in the diagnosis of infected total joint prostheses was examined in 28 patients and compared with sequential [99mTc]HDP/[111In]WBC scintigraphy and aspiration arthrography. The sensitivity of preoperative aspiration cultures was 12%, with a specificity of 81% and an accuracy of 58%. The sensitivity of [111In]WBC imaging alone was 100%, with a specificity of 50% and an accuracy of 65%. When correlated with the bone scintigraphy and read as sequential [99mTc]HDP/[111In]WBC imaging, the sensitivity was 88%, specificity 95%, and accuracy 93%. This study demonstrates that [111In]WBC imaging is an extremely sensitive imaging modality for the detection of occult infection of joint prostheses. It also demonstrates the necessity of correlating [111In]WBC images with [99mTc]HDP skeletal scintigraphy in the detection of occult periprosthetic infection.     

Time course of myocardial infarction evaluated by indium-111-antimyosin monoclonal antibody scintigraphy: clinical implications and prognostic value.

To investigate the clinical implications of 111In-antimyosin antibody scintigraphy in the chronic stage of myocardial infarction, 34 studies were performed in 26 patients with 36 infarcts of various infarct ages. The infarcts were divided into three groups according to time from onset of chest pain to scintigraphy. Positive antimyosin images were obtained in 93% of Group I patients (3 days to 1 mo), 71% of Group II patients (1.5 mo to 1 yr) and none were obtained from Group III patients (1.5-6 yr). A negative correlation was observed between antimyosin uptake and the time after myocardial infarction. In Group II, patients with coronary artery patency and patients showing redistribution on exercise 201TI scintigraphy were more likely to have positive antimyosin images compared to patients without these features. Recurrent angina may also relate to chronic antimyosin uptake. Indium-111-antimyosin antibody scintigraphy may be a useful method in assessing the course of myocardial infarction and for the patient follow-up.     

Sequential technetium-99m sulfur colloid/indium-111 white blood cell imaging in macroglobulinemia of Waldenstrom

Technetium-99m sulfur colloid (SC) and indium-111 labeled leukocyte (In-111 WBC) scintigraphy was performed on a 77-year-old female patient to rule out a left periprosthetic infection. Anterior Tc-99m SC and In-111 WBC images of the pelvis and femurs revealed no abnormal deposition of radiotracer about the Austin-Moore prosthesis. Absent radiotracer uptake, however, was demonstrated within the left hemipelvis. A left iliac bone marrow aspirate and biopsy revealed a lymphoplasmacytic infiltrate consistent with Waldenstrom's macroglobulinemia.