technetium-tc-99m-exametazime and Colitis

Knowledge of the distribution of disease in patients with inflammatory bowel disease is important because it has diagnostic, prognostic, and therapeutic implications. We studied 215 patients with 99mTc-HMPAO-white blood cell scans, of whom 80 had Crohn's disease (CD), 34 had active ulcerative colitis (UC), and 31 were controls. In our 77 cases of active CD, uptake was seen exclusively in the small bowel in 18% of patients, only the large bowel in 44%, and both the large and small bowel in 38% of patients. Discontinuous colitis was seen in 63 of these patients. In the 29 cases of active UC, the uptake involved the entire colon in 50% of patients, extended farther than the sigmoid in 27% of patients, and was limited to the rectosigmoid in 23%. In the 29 cases of active UC, four of the scans incorrectly revealed discontinuous accumulation of 99mTc-HMPAO-WBC. In 31 controls, no significant colonic uptake was seen. Isolated small bowel involvement with CD is observed less frequently in children undergoing 99mTc-HMPAO-WBC scanning than in adults. In children, the segmental distribution of inflammation as depicted with 99mTc-HMPAO-WBC is similar to the radiologic distribution.

Topics: Adolescent; Adult; Child; Child, Preschool; Colitis; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Female; Humans; Ileitis; Leukocytes; Male; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Exametazime

This study was undertaken to evaluate technetium 99m (Tc 99m) hexamethyl propylenamine oxime (HMPAO)-labeled leukocyte scintigraphy for assessment of disease extent and activity in acute colitis.. Twenty-seven patients, hospitalized because of acute watery and/or bloody diarrhea, were investigated using both total colonoscopy and Tc 99m HMPAO-labeled leukocyte scintigraphy within 48 hours after admittance.. Final diagnoses were ulcerative colitis in 14 patients, Crohn's disease in 7 patients, and infectious colitis in 6 patients. Using colonoscopy as the reference method, the maximum extent of colitis was correctly assessed by the leukocyte scan in 18 patients (67 percent), although rectal engagement was not visualized in 5 (19 percent). In six additional patients, there was almost complete agreement between the two methods. One other patient, with leftsided ulcerative colitis, was erroneously assessed as having total extent. Two other patients (one with Crohn's colitis and one with infectious colitis) had different segments incorrectly assessed. Sensitivity, specificity, and diagnostic accuracy of scintigraphy in detecting active inflammatory segments were 0.85, 0.83, and 0.85, respectively. Intensity of inflammatory activity assessed by the leukocyte scan correlated significantly with colonoscopic assessment (r = 0.719; P < 0.0001).. Information regarding extent, localization, and disease activity in patients with acute colitis of inflammatory or infectious origin may be satisfactorily obtained using Tc 99m HMPAO-labeled leukocyte scanning. The noninvasive nature of the method makes it an attractive early alternative to other investigational procedures such as total colonoscopy or barium examination, particularly in cases with an established diagnosis of inflammatory bowel disease.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Colitis; Colonoscopy; Female; Humans; Leukocytes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Technetium Tc 99m Exametazime; Time Factors

Evaluating the efficacy of therapy in experimental inflammatory bowel disease (IBD) requires information about inflammatory activity in bowel segments or leukocyte recruitment and about kinetics in the follow-up of treatment. This study evaluated a noninvasive scintigraphic technique able to assess neutrophil trafficking in a mouse model of dextran sulfate sodium (DSS)-induced colitis.. Groups of 4 BALB/c mice were assessed at baseline and after 1, 3, 5, and 8 d of treatment with DSS. Donor neutrophils were harvested by rinsing of the peritoneal cavity with phosphate-buffered saline 5 h after intraperitoneal injection of proteose peptone contained in phosphate-buffered saline and labeled with freshly prepared (99m)Tc-hexamethylpropylene amine oxime (HMPAO). Pinhole SPECT of the abdomen was performed 1 h after reinjection of 50 MBq of labeled neutrophils. In addition, the severity of inflammation was determined by histologic examination. The possibilities of the technique were illustrated by scintigraphic assessment of neutrophil trafficking with and without blocking of neutrophil migration by a CD97 monoclonal antibody in mice with DSS-induced colitis.. Colonic uptake of (99m)Tc-HMPAO neutrophils was determined with dedicated animal pinhole SPECT in mice with DSS-induced colitis and correlated well with histologic findings (R = 0.81) and wet colon weight (R = 0.87) and moderately with clinical weight loss (R = 0.62). The neutrophil uptake ratio was reduced significantly (P < 0.01) by blocking of neutrophil migration capacity with the CD97 antibody.. Animal pinhole SPECT can be used to study inflammatory activity and neutrophil recruitment in vivo in experimental colitis.

Topics: Animals; Colitis; Dextran Sulfate; Disease Models, Animal; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Neutrophils; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

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.. 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.. 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).. 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.

Topics: Animals; Biphenyl Compounds; Colitis; Female; Fluorodeoxyglucose F18; Granulocytes; Isotope Labeling; Leukotriene B4; Neutrophils; Oligopeptides; Organ Specificity; Pyridines; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tetrazoles; Tissue Distribution; Whole-Body Counting

Topics: Abdominal Pain; Aneurysm, Infected; Colitis; Humans; Leukocytes; Middle Aged; Radiography; Radionuclide Imaging; Radiopharmaceuticals; Salmonella Infections; Technetium Tc 99m Exametazime

Radiolabeled autologous leukocytes (WBCs) are the gold standard for imaging inflammatory bowel disease (IBD). For the rapid and adequate management of patients with IBD, there is need for a new agent at least as good as radiolabeled WBCs, but easier to prepare and without its inherent risks. In this study, the potential of interleukin-8 (IL-8) labeled with (99m)Tc using hydrazinonicotinamide (HYNIC) to image IBD was investigated in a rabbit model of acute colitis and compared with that of (99m)Tc-HMPAO-labeled granulocytes.. In rabbits with chemically induced acute colitis, inflammatory lesions were scintigraphically visualized after injection of either IL-8 or purified granulocytes, both labeled with (99m)Tc. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. Four hours after injection, the rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. The dissected colon was imaged and the inflammatory lesions were scored macroscopically. For each affected colon segment, the colitis index (affected colon-to-normal colon uptake ratio, CI) was calculated and correlated with the macroscopically scored severity of inflammation.. Both agents visualized the colitis within 1 h after injection. (99m)Tc-HYNIC-IL-8 images of the colonic abnormalities were more accurate and the intensity of uptake in the affected colon continuously increased until 4 h after injection, whereas no further increase 1 h after injection was noticed scintigraphically for (99m)Tc-HMPAO-granulocytes. The absolute uptake in the affected colon was much higher for IL-8 than for the radiolabeled granulocytes with the percentage injected dose per gram (%ID/g) 0.41 +/- 0.04 %ID/g and 0.09 +/- 0.05 4 %ID/g h after injection, respectively. With increasing severity, the CI at 4 h after injection for (99m)Tc-HYNIC-IL-8 was 4.4 +/- 0.6, 13.5 +/- 0.5, and 25.8 +/- 1.0; for granulocytes, the CI at 4 h after injection was 1.5 +/- 0.1, 3.4 +/- 0.2, and 6.4 +/- 0.5, respectively. The CI correlated with the severity of the inflammation (r = 0.95, P < 0.0001 for IL-8; r = 0.95, P < 0.0001 for granulocytes).. Within 1 h after injection, visualization of the extent of colonic inflammation in vivo was possible with (99m)Tc-HYNIC-IL-8 and (99m)Tc-HMPAO-granulocytes. Within 2 h after injection, (99m)Tc-IL-8 allowed a good evaluation, and within 4 h after injection, a meticulous evaluation of the severity of IBD. Although (99m)Tc-HMPAO-granulocytes were able to delineate the extent of IBD within 2 h after injection, an accurate estimation of severity of inflammation was not possible. (99m)Tc-HYNIC-IL-8 is an inflammation-imaging agent that showed promising results in this study. (99m)Tc-IL-8 can be prepared off-the-shelf and yields excellent imaging with high target-to-background ratios.

Topics: Acute Disease; Animals; Colitis; Colon; Female; Gamma Cameras; Granulocytes; Hydrazines; Interleukin-8; Niacinamide; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Technetium; Technetium Tc 99m Exametazime; Trinitrobenzenesulfonic Acid

Scintigraphic techniques are routinely used for the evaluation of the extent and severity of inflammatory bowel disease. Currently, the radiopharmaceutical of choice is 99mTc-hexamethyl propyleneamine oxime (HMPAO)-leukocytes. We studied the imaging potential of two recently developed 99mTc-labeled agents, polyethylene glycol (PEG)-coated liposomes and hydrazinonicotinate (HYNIC) IgG, in a rabbit model of acute colitis, and compared them with that of 99mTc-labeled, granulocyte-enriched (>90%), white blood cells.. Acute colitis was induced in rabbits by retrograde instillation of trinitrobenzene sulfonic acid. After 48 hr, 37 MBq of each radiopharmaceutical was administered intravenously. Gamma camera images were taken at 0, 1, 2, 4, 10 and 24 hr. At 4 and 24 hr postinjection, groups of rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. For each affected 5-cm segment, the colitis index (CI, affected-to-normal-colon-uptake ratio) was calculated and correlated to the macroscopically scored severity of inflammation.. All three agents visualized the colitis lesions within 1 hr postinjection. The CI correlated with the severity of the abnormalities. With increasing severity, the CI at 4 hr postinjection for liposomes was 3.89+/-0.73, 4.41+/-0.47 and 5.76+/-0.65; for IgG 1.67+/-0.08, 3.92+/-0.44 and 6.14+/-0.65; and for granulocytes 2.90+/-0.09, 6.15+/-0.96 and 9.36+/-3.35. For liposomes, the CI further increased during 24-hr postinjection to 6.56+/-0.84, 8.50+/-0.53 and 10.61+/-1.34, respectively. The CI for the other two agents did not change significantly with time.. In this rabbit model, 99mTc-labeled granulocytes, IgG and liposomes all rapidly visualized colonic inflammation. Granulocytes and liposomes showed the highest CI. Technetium-99m-labeled PEG-liposomes may be an attractive alternative for labeled leukocytes to image inflammatory bowel disease, because they can be prepared off the shelf and no handling of blood is required.

Topics: Animals; Autoradiography; Colitis; Drug Carriers; Female; Granulocytes; Immunoglobulin G; Liposomes; Organotechnetium Compounds; Polyethylene Glycols; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tissue Distribution

A child with colitis was treated for Crohn's disease, diagnosed on history, clinical and colonoscopic findings, radiolabelled white cell bowel scan, and colonic histology. After septicaemia caused by an unusual organism, further investigation lead to a diagnosis of chronic granulomatous disease (CGD). The granulomatous colitis of CGD is clinically, histologically, and on white cell scanning, indistinguishable from that in Crohn's disease and should be considered in atypical cases. Infection with unusual 'pseudomonads' should prompt the exclusion of this disorder.

Topics: Burkholderia Infections; Child, Preschool; Colitis; Crohn Disease; Diagnosis, Differential; Granulomatous Disease, Chronic; Humans; Leukocytes; Male; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Technetium Tc 99m Exametazime

Using a novel labeling technique with technetium 99m-hexamethyl propylene amine oxine, we studied 29 patients with known or suspected Crohn's disease. Technetium 99m-hexamethyl propylene amine oxine leukocyte scanning (99mTc scan) was prospectively compared with the results of independently performed radiologic, endoscopic, and histologic examinations, and with findings at surgery, to assess the clinical usefulness of this technique to localize inflammatory lesions. In addition, uptake of technetium 99m-hexamethyl propylene amine oxine in the bowel was graded by comparing it with the uptake in liver and bone marrow and correlating this with established parameters of disease activity. The viability of homologous labeled leukocytes was greater than 95%. Less than 5% of lymphocytes were found in the final preparation. It was found that 45% +/- 12% of the label was bound to granulocytes, and 98% of the unbound label was washed off before reinjection. The results of 99mTc scan revealed a good correlation with those of barium enema (r = 0.880, p less than 0.001), of endoscopy/surgery (r = 0.983, p less than 0.001), and of all combined reference methods (r = 0.981, p less than 0.001). Activity as determined by 99mTc scan was weakly correlated with the results of Crohn's disease activity index (r = 0.559, p less than 0.01), van Hees index (r = 0.606, p less than 0.01), and erythrocyte sedimentation rate (r = 0.456, p less than 0.05) in 24 patients with proven Crohn's disease. The correlation was improved when the 99mTc scan was compared with a combination of these activity parameters and C-reactive protein (r = 0.781, p less than 0.001). Extraintestinal manifestations (joints) and complications (cholecystitis) were also identified correctly by the 99mTc scan. The study demonstrates that leukocyte scanning with technetium 99m-hexamethyl propylene amine oxine as a label can reliably assess the location and, to a lesser degree, activity of Crohn's disease. This technique is more convenient and provides images far superior to those produced by indium 111-labeled leukocyte scanning.

Topics: Adolescent; Adult; Barium Sulfate; Colitis; Crohn Disease; Enema; Female; Granulocytes; Humans; Ileitis; Intestines; Male; Middle Aged; Organometallic Compounds; Oximes; Radiography; Radionuclide Imaging; Technetium; Technetium Tc 99m Exametazime

Leukocytes labeled with technetium-99m hexamethylpropyleneamine oxime (HMPAO) were used in 100 patients: 32 with suspected inflammatory bowel disease, 17 with fever of unknown origin, 21 with suspected abdominal sepsis, 20 with suspected bone sepsis, seven with bronchiectasis, and three with recent myocardial infarction. The distribution of activity in patients subsequently shown not to have inflammatory bowel disease was similar to that previously described for indium-111-labeled leukocytes. However, in this study, activity was also seen in the kidneys and bladder and occasionally the gallbladder on both early (1-3 hours) and late (24 hours) views, and in the colon in late views. Migration of Tc-99m-labeled granulocytes was seen in inflammatory disease as early as 30 minutes after injection, while normal bowel activity was not seen before 4 hours. The sensitivity of Tc99m-labeled leukocytes in the detection of inflammation was 100%, the specificity was 95%.

Topics: Colitis; Crohn Disease; Fever of Unknown Origin; Humans; Inflammation; Leukocytes; Organometallic Compounds; Osteitis; Oximes; Radionuclide Imaging; Technetium; Technetium Tc 99m Exametazime