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     

Scintigraphic evaluation of the painful prosthetic joint: a comparison of gallium-67 citrate and indium-111 labelled leucocyte imaging

The radiopharmaceuticals gallium-67 and indium-111 labelled leucocytes have been compared in 15 patients with a painful joint prosthesis in an attempt to identify those patients with periprosthetic infection. Gallium-67 images were abnormal in five out of six patients with periprosthetic infection and normal in seven out of nine without evidence of infection. Indium-111 leucocyte images were abnormal in three out of six patients with infection and normal in all nine patients without infection. Indium-111 labelled leucocyte imaging is technically more difficult to perform than gallium-67 imaging. This, combined with the higher sensitivity of gallium-67 imaging for infection around a prosthetic joint, leads us to conclude that gallium-67 imaging is superior to indium-111 leucocyte imaging in identifying infection as a cause of a painful prosthetic joint.     

Simultaneous administration of111In-human immunoglobulin and99mTc-HMPAO labelled leucocytes in inflammatory bowel disease

Technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled leucocytes and indium-111 polyclonal immunoglobulin (IgG) were simultaneously injected into a group of 27 patients routinely referred for the investigation of inflammatory bowel disease (IBD). Ten-minute anterior abdomen and tail on detector views were obtained at 30 min, 4 h and 24 h p.i. of both tracers. The diagnosis of IBD was obtained in all cases by endoscopy with biopsy and/or surgery. Images were blindly evaluated by two experienced observers who only knew of the clinical suspicion of IBD. IBD was confirmed in 20 patients (12 with Crohn's disease and eight with ulcerative colitis). Sensitivity, specificity and accuracy were 100%, 85% and 96% respectively for labelled leucocytes and 70%, 85% and 74% for IgG. Both IgG and leucocyte scans were normal in six out of seven patients in whom a diagnosis of IBD was excluded; the remaining patient, with ischaemic colitis, was falsely positive with both agents. As far as disease extension is concerned, the IgG study localized 27 diseased segments, whereas 49 were seen with the leucocyte study. Eighty-four segments were normal and 25 showed tracer uptake with both agents. Twenty-four were positive only with the leucocyte study and two were positive only with the IgG study. Agreement between the agents was 80.7%. These results confirm that¹¹¹In-human polyclonal scintigraphy is less sensitive than^99mTc-HMPAO scintigraphy both for the diagnosis of IBD and in the evaluation of disease extension. Nevertheless, if leucocyte labelling is not available, labelled IgG can be used only for diagnostic purposes.     

Donor leucocyte imaging in patients with AIDS: a preliminary report

Four patients with the acquired immunodeficiency syndrome (AIDS) and fever were investigated using donor leucocyte scans. The lung/liver and lung/spleen uptake ratios in these patients were compared with the uptake ratios in donor leucocyte scans in seven neutropenic (non-AIDS) patients and five patients who had autologous leucocyte scans performed over the same time period. For all scans indium-111-oxime-labelled leucocytes were used, except for one AIDS patient in whom technetium-99m hexamethyl-propylene amine oxide (HMPAD)-labelled donor leucocytes were used. There were no adverse reactions to the donor cell infusions. Two patients had repeat studies 8 weeks apart (from different donors) without ill effect. There were no differences in the¹¹¹In uptake ratios between the three groups. There were three positive studies in the patients with AIDS, and these elucidated the cause of the pyrexia in all three. The negative case is more difficult to confirm, but the clinical course and the absence of focal disease on post-mortem have been taken to support the scan findings. There was no difference in the acceptability of the technique or the distribution of the labelled leucocytes between the AIDS and non-AIDS patients. Donor leucocyte imaging of patients with AIDS is probably more effective and considerably less hazardous for technical staff than autologous leucocyte methods. This study demonstrates that the technique can be applied successfully to patients with AIDS.     

Donor leucocyte imaging in patients with AIDS: a preliminary report

Four patients with the acquired immunodeficiency syndrome (AIDS) and fever were investigated using donor leucocyte scans. The lung/liver and lung/spleen uptake ratios in these patients were compared with the uptake ratios in donor leucocyte scans in seven neutropenic (non-AIDS) patients and five patients who had autologous leucocyte scans performed over the same time period. For all scans indium-111-oxime-labelled leucocytes were used, except for one AIDS patient in whom technetium-99m hexamethyl-propylene amine oxide (HMPAD)-labelled donor leucocytes were used. There were no adverse reactions to the donor cell infusions. Two patients had repeat studies 8 weeks apart (from different donors) without ill effect. There were no differences in the 111In uptake ratios between the three groups. There were three positive studies in the patients with AIDS, and these elucidated the cause of the pyrexia in all three. The negative case is more difficult to confirm, but the clinical course and the absence of focal disease on post-mortem have been taken to support the scan findings. There was no difference in the acceptability of the technique or the distribution of the labelled leucocytes between the AIDS and non-AIDS patients. Donor leucocyte imaging of patients with AIDS is probably more effective and considerably less hazardous for technical staff than autologous leucocyte methods. This study demonstrates that the technique can be applied successfully to patients with AIDS.     

Prospective investigation of radiologic methods in the diagnosis of intra-abdominal abscesses

A prospective investigation of conventional abdominal radiography, ultrasonography, computed tomography and 111In-labelled leucocyte scintigraphy was performed in 40 patients suspected of having an intra-abdominal abscess. There were 23 confirmed abscesses in the material. When conventional abdominal radiography indicated an abscess, such a lesion was usually present. The ability of abdominal radiography to exclude an abscess was, however, low. Both ultrasonography and 111In-labelled leucocyte scintigraphy detected 65 to 85 per cent of the confirmed abscesses, but both also revealed many abscess-like areas in patients where no unequivocal abscess was confirmed at follow-up. Computed tomography was, when employed as a single method, the most reliable one both to show and to exclude an abscess, However, the combination of ultrasonography and 111In-labelled leucocyte scintigraphy disclosed all the lesions demonstrated by any one of the four methods used in the investigation.     

Leucocyte scanning: preparation and labelling of leucocytes with 111-Indium oxide and its clinical application

A method for the concentration of leucocytes from blood and labelling of the separated cells with 111-Indium oxine is described. This method guaranteed a good preparation. On average there were 64.8% of leucocytes from the blood in the concentrate. The yield of the labelling averaged 93%. Seventy-two patients from various departments were examined to test the clinical application of the labelled leucocytes in the diagnosis of inflammatory diseases. The results obtained led to the formulation of six indications for the appropriate application of leucocyte scanning in everyday clinical routine.     

99Tcm-HMPAO labelled leucocytes: comparison with 111In-tropolonate labelled granulocytes

The lipophilic complex, 99Tcm-hexamethylpropyleneamine oxime (HMPAO) is an efficient leucocyte label, and labels granulocytes with more stability than mononuclear leucocytes. The recovery of 99Tcm-HMPAO granulocytes, expressed as the percentage of injected granulocyte-associated activity circulating as granulocyte-associated activity 40-45 min after injection, was 37% (S.E. 3%), similar to the recovery of 111In-labelled granulocytes isolated and labelled in plasma using tropolone. The T1/2 of 99Tcm-HMPAO labelled granulocytes in blood was 4.4 h (S.E. 0.4 h), less than that of 111In-labelled granulocytes, although when a correction was made for 99Tcm elution, it was 6.4 h. The initial biodistribution of 99Tcm-labelled leucocytes was similar to 111In-labelled granulocytes, with a rapid initial lung transit, prominent splenic activity, bone marrow activity and minimal hepatic activity, although, unlike 111In, 99Tcm activity was also seen in urine, occasionally in the gallbladder, and, from about 4 h, consistently in the colon. Bone marrow activity was particularly prominent with 99Tcm. About 6% of 99Tcm was excreted in the faeces up to 48 h after injection, and about 17% in urine up to 24 h. The time-activity curves of reticuloendothelial activity up to 24 h were broadly similar for the two labelled cell preparations, and the differences that were observed can be explained on the basis of a higher rate of 99Tcm elution. Clinical information given by the two agents was similar in 27 of 30 patients who received both. Of the three who gave different information, one received 111In-labelled granulocytes which were considered to be functionally suboptimal and two, with inflammatory bowel disease, showed different distributions of abnormal bowel activity. We conclude that with respect to granulocyte kinetics and clinical data, 99Tcm-HMPAO labelled leucocytes are comparable with 111In-tropolonate labelled granulocytes.     

99mTc-human immunoglobulin (HIG)--first results of a new agent for the localization of infection and inflammation

Technetium (99mTc) labelled, polyclonal human immunoglobulin (HIG) is a new agent that detects focal infection and inflammation. This new agent was compared in 40 patients with the accepted standard, namely 111In-oxine-labelled leucocytes. This comparison resulted in a sensitivity of 94% and a specificity of 96% for 99mTc-HIG when 111In-oxine leucocytes were defined as giving the true result. The new agent was shown to localize both sepsis and active inflammatory bowel disease (IBD). There was 100% concordance in the 16 patients with IBD who were imaged with both 99mTc-HIG and 111In-oxine leucocytes. Discordant results were obtained in one case of suspected osteomyelitis, which was false-positive on the 99mTc-HIG scan, and one case of pyrexia of unknown origin when the 99mTc-HIG was false-negative and the 111In-oxine leucocyte scan demonstrated accumulation of tracer in the caecum at 24 h post-injection. Normal distribution for 99mTc-HIG demonstrated activity in the kidneys and bladder and that 50% of the tracer is cleared through the kidneys during the first 24 h post-injection. There were no major or minor side-effects.     

Leucocyte scanning: Preparation and labelling of leucocytes with 111-Indium oxine and its clinical application

A method for the concentration of leucocytes from blood and labelling of the separated cells with ¹¹¹-Indium oxine is described. This method guaranteed a good preparation. On average there were 64.8% of leucocytes from the blood in the concentrate. The yield of the labelling averaged 93%. Seventy-two patients from various departments were examined to test the clinical application of the labelled leucocytes in the diagnosis of inflammatory diseases. The results obtained led to the formulation of six indications for the appropriate application of leucocyte scanning in everyday clinical routine.     

Indium-111-labeled leukocyte localization in hematomas: a pitfall in abscess detection

Indium-111-labeled white-blood-cell scanning is a useful modality in abscess detection and has replaced gallium scanning in many institutions. Sensitivities of 72% to 90% and specificities of 90% to 100% have been reported. In searching for abscesses seven cases of indium-111-labeled leukocyte uptake were encountered in collections subsequently proved to be noninfected hematomas. Abundant red blood cells with few or no white blood cells, no bacteria, and a benign clinical course identified these noninfected hematomas. Five of the patients were being treated with hemodialysis and three were recent allograft recipients. The results indicate some limitation and nonspecificity in indium-111 scanning, despite its many benefits.     

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.     

99mTc-human immunoglobulin (HIG) — first results of a new agent for the localization of infection and inflammation

Technetium (^99mTc) labelled, polyclonal human immunoglobulin (HIG) is a new agent that detects focal infection and inflammation. This new agent was compared in 40 patients with the accepted standard, namely¹¹¹In-oxine-labelled leucocytes. This comparison resulted in a sensitivity of 94% and a specificity of 96% for^99mTc-HIG when¹¹¹In-oxine leucocytes were defined as giving the true result. The new agent was shown to localize both sepsis and active inflammatory bowel disease (IBD). There was 100% concordance in the 16 patients with IBD who were imaged with both^99mTc-HIG and¹¹¹In-oxine leucocytes. Discordant results were obtained in one case of suspected osteomyelitis, which was false-positive on the^99mTc-HIG scan, and one case of pyrexia of unkown origin when the^99mTc-HIG was false-negative and the¹¹¹In-oxine leucocyte scan demonstrated accumulation of tracer in the caecum at 24 h post-injection. Normal distribution for^99mTc-HIG demonstrated activity in the kidneys and bladder and that 50% of the tracer is cleared through the kidneys during the first 24 h post-injection. There were no major or minor side-effects.     

False positive localisation of indium-111 granulocytes in colonic carcinoma

Indium-111 leucocyte scanning has been shown to be a highly accurate technique for detecting abscesses and assessing inflammatory bowel disease. We have encountered two cases of colonic carcinoma which presented as suspected inflammatory bowel disease and were found to localise 111In-labelled granulocytes. Histology revealed an acute inflammatory infiltrate in these tumours. These results indicate that 111In granulocyte scanning has limitations in the diagnosis of inflammatory bowel disease.     

Indium labelled leucocyte scintigraphy in occult infection: a comparison with ultrasound and computed tomography

A review of five year's experience of the use of 111Indium labelled leucocyte scintigraphy (111In WBC) in the investigation of suspected sepsis is presented. The results of 257 111In WBC scans for which a definitive diagnosis was subsequently established were available for analysis. The findings are compared with those of ultrasound (130 cases) and computed tomography (82 cases) and the final clinical outcome. The sensitivity and specificity of the 111In WBC for the series were 97% and 91% respectively. The major cause of the false positive 111In WBC results was activity within the bowel not due to infection. Thrombus within the inferior vena cava caused a false positive 111In WBC result: this is previously undescribed. There were a large number of incorrect ultrasound results, particularly with abdominal and pelvic abscesses, pyelonephritis, peritonitis and non-infected fluid collections, showing that a negative ultrasound cannot exclude infection. The relative merits of the three modalities are discussed, emphasizing that more than one technique may be required to establish a diagnosis.     

Indium-granulocyte scanning in the painful prosthetic joint

The value of indium-111-labeled granulocyte scanning to determine the presence of infection was assessed in 50 prosthetic joints (41 of which were painful) in 40 patients. Granulocytes were obtained from the patients' blood and labeled in plasma with indium 111 tropolonate. Abnormal accumulation of indium 111 in the region of the prosthesis was noted. Proven infection occurred in 11 prostheses, and all of the infections were detected by indium-111-labeled granulocyte scanning. Nineteen were not infected (including nine asymptomatic controls) and only two produced false-positive scans. This represents a specificity of 89.5%, sensitivity of 100%, and overall accuracy of 93.2%. These results compare favorably with plain radiography. There was no radiologic evidence of infection in three of the infected prostheses, and 10 of the noninfected prostheses had some radiologic features that suggested sepsis. We conclude that indium-granulocyte scanning can reliably detect or exclude infection in painful prosthetic joints and should prove useful in clinical management.     

Leucocyte and contaminant cell-bound activities resulting from the labelling of leucocytes with 111In-oxine

A simple method is described for estimating the activities bound to leucocytes, erythrocytes, platelets and the free activity, as resulted from the preparation and labelling of leucocytes with 111In-oxine. Measurements are required only of 111In activity, suspension volumes, and platelet concentrations. The limitations of the method are discussed. When blood from a normal volunteer was labelled by an 111In-oxine manufacturer's recommended technique, the greatest proportion of activity was bound to leucocytes, and in addition, a significant proportion of the activity was found to be associated with platelets. If the number of centrifugations between sedimentation and labelling was reduced from two to one, the proportion of free activity increased at the expense of a reduction in leucocyte activity, but the platelet activity remained unchanged. The relative distribution of cell-bound and free activities was independent of the relative centrifugal force (85-450 g), and of the time (15-30 min) and the suspension volume (5-10 ml) used to incubate the cells with 111In-oxine.     

Indium-111 labelled white blood cell scintigraphy in cranial and spinal septic lesions

Cranial and spinal infections are severe events that require timely diagnosis and treatment. Physical and neurological examination, laboratory tests and radiological imaging may be insufficient for assessing cranial and spinal septic lesions. This study aimed to evaluate the accuracy of indium-111 white blood cell (WBC) scan in assessing the presence of leucocytes in intracranial and spinal lesions, and in the diagnosis, management and follow-up of primary, post-traumatic and post-surgical infections. One hundred and twenty-four subjects were included in the study (48 with post-traumatic or post-surgical lesions, 73 with primary cerebral lesions, and 3 with spinal lesions). All patients underwent a diagnostic work-up including planar scans with 111In-labelled WBCs, at 4 and 24 h post tracer injection. All subjects underwent surgical treatment. Patients who did not recover from the infection as suggested by clinical evolution underwent further treatment (up to three times) and further WBC scans (up to four times). WBC scintigraphy correctly identified all the areas of leucocyte accumulation, as confirmed after surgery. WBC scintigraphy also correctly excluded the presence of leucocytes in all other lesions, as demonstrated at surgery. The results of this study confirm the accuracy of WBC scan for the assessment of patients with cranial and spinal lesions, in whom the demonstration of leucocyte accumulation can ease the diagnosis of infection, and indicate that the method is also accurate for the follow-up and management of neurosurgical patients.     

Clinical validation of the avidin/indium-111 biotin approach for imaging infection/inflammation in orthopaedic patients.

We report here the results of a validation study of the avidin/indium-111 biotin approach in patients with skeletal lesions. This study involved 54 patients with orthopaedic conditions: 20 patients with intermediate suspected osteomyelitis of the trunk, 19 patients with infection/inflammation of prosthetic joint replacements, and 15 patients with suspected osteomyelitis of appendicular bones. Avidin (3 mg) was injected as an i.v. bolus, followed 4 h later by 111In-biotin; imaging was acquired 30 min and 16-18 h after administration of 111In-biotin. Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled leucocyte scintigraphy was performed in 39/54 patients. The overall sensitivity of the avidin/111In-biotin scan was 97.7% (versus 88.9% for 99mTc-HMPAO leucocyte scintigraphy). While the diagnostic performance of avidin/111In-biotin scintigraphy was similar to that of 99mTc-HMPAO leucocyte scintigraphy in patients with prosthetic joint replacements or osteomyelitis of appendicular bones, the avidin/111In-biotin approach clearly performed better than 99mTc-HMPAO leucocyte scintigraphy in patients with suspected osteomyelitis of the trunk (100% sensitivity, specificity and accuracy versus 50% sensitivity, 100% specificity and 66.7% accuracy for 99mTc-HMPAO-leucocyte scintigraphy). These results demonstrate the feasibility of the avidin/111In-biotin approach for imaging sites of infection/inflammation in the clinical setting. Although no systematic advantages of avidin/111In-biotin scintigraphy were found versus 99mTc-HMPAO leucocyte scintigraphy, the newer scintigraphic method is more practicable and involves lower biological risk for the operators.     

Identification of factors affecting technetium 99m leucocyte labelling by phagocytic engulfment and development of an optimal technique

Human autologous leucocytes can be simply and reproducibly labelled by phagocytic engulfment of technetium 99m stannous colloid with high leucocyte-labelling efficiency (LLE), similar human biodistribution to indium-111-oxine labelled leucocytes and good cell viability. A mean particle size of 2.1 microns is optimal for phagocytosis and the most important parameter in maintaining reproducibly high neutrophil uptake. It is more critical than hitherto appreciated. When such variables as type of colloid, purity of starting materials, speed of mixer rotation when preparing colloid and labelling leucocytes, heparin concentration, freshness of colloid preparation, type of sterilising membrane filter used and incubation time of cells with colloid are rigidly controlled, consistent labelling efficiencies in excess of 90% can be obtained with neutrophil predominance. The lyophilised kit tested produced suboptimal results.