99Tcm-HMPAO leucocyte scintigraphy in the diagnosis of bone infection

The utility of 99Tcm-HMPAO leucocytes has been studied in combination with 99Tcm-MDP bone scanning in the diagnosis of bone infection in a series of 50 patients with a clinical suspicion of bone infection. Thirty-three patients were referred to our Service from the Department of Orthopaedic Surgery (Group A) and seventeen from the Infectious Disease Unit (Group B). A total of 52 lesion sites were studied. The leucocyte and bone studies were performed within four days. The leucocyte scan was obtained at 30-60 min and 4-6 h after i.v. injection of 370 +/- 74 MBq of 99Tcm-HMPAO leucocytes. After confirming the scintigraphic findings, the results obtained were: Group A, 12 true positive, 21 true negative and 2 false positive; and in Group B, 5 true positive, 9 true negative and 4 false negative. The overall sensitivity was 80.9% with a specificity of 93.7%. Although the high bone marrow activity seen with 99Tcm-HMPAO leucocytes may reduce sensitivity, very good results were obtained in bone infection. The use of 99Tcm means great progress in the radiolabelling of white blood cells in terms of availability and better image quality. The combination of 99Tcm-HMPAO leucocytes and 99Tcm-MDP can be recommended as one of the most suitable methods for use in the diagnosis of bone infection, especially in patients with previous bone disease.     

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.     

Indium-111 tropolonate leucocyte scanning in the detection of intra-abdominal abscesses

Indium-111 leucocyte scanning is established as an accurate method for localising intra-abdominal abscesses. With the currently available cell labelling techniques there is a variable and significant delay in localisation of abscesses which is a major disadvantage in comparison with ultrasound or computed tomography. We have examined the speed and accuracy of localisation of leucocytes labelled in plasma with a new chelating agent, indium-111 tropolonate, in 90 patients with suspected intra-abdominal abscess. In 50 patients a comparison with ultrasound was made. Nineteen patients had abscesses. The sensitivity and specificity of labelled leucocytes were 95% and 99%, respectively. Comparative results for ultrasound were 60% and 83%. In nine out of 10 patients with abscesses scanned sequentially from 40 min after return of the labelled cells, activity corresponding to the abscess was already visible on the 40 min scan. These results demonstrate that indium-111 plasma labelled leucocyte scanning is both rapid and an accurate method of detecting abscesses.     

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.     

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.     

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     

Clinical comparison of 99Tcm-HMPAO labelled leucocytes and 99Tcm-nanocolloid in the detection of inflammation

Forty-five patients with various inflammatory diseases were imaged with 99Tcm-HMPAO labelled leucocytes and 99Tcm-nanocolloid within 7 days. The overall sensitivity of 99Tcm-leucocytes was 97% and that of 99Tcm-nanocolloid 59% and both agents had a 100% specificity. The 99Tcm-leucocyte method showed reliable results in various inflammatory and infectious conditions, and seems suitable as a primary imaging method. On the contrary, 99Tcm-nanocolloid cannot be recommended for use in inflammatory bowel diseases, soft tissue abscesses or prosthetic vascular graft infections. However, 99Tcm-nanocolloid gave reliable information in inflammatory and infectious bone and joint diseases in which it had a 90% sensitivity and 100% specificity. In those lesions the 99Tcm-nanocolloid method may be useful, because it is simple, fast and cheap. Yet, further evaluation is needed.     

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.     

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 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.     

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.     

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.     

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     

Chronic osteomyelitis: diagnosis with tech netium-99m-d,l-hexamethylpropylene amine oxime labelled leucocytes

To evaluate the diagnostic value of technetium-99md,l-hexamethylpropylene amine oxime (HMPAO) labelled leucocytes in combination with a^99mTc-methylene diphosphonate (MDP) bone scan in the detection of chronic osteomyelitis, we retrospectively reviewed 55 patients. Prior to the^99mTc-d,I-HMPAO labelled leucocyte scan, all patients underwent a^99mTc-MDP bone scan. The correct diagnosis was confirmed by long-term clinical follow-up (n=29) or by bacteriological cultures (n=26). We found an overall sensitivity of 94%, a specificity of 91% and an accuracy of 92% for^99mTc-d,l-HMPAO labelled leucocyte scintigraphy in the diagnosis of chronic osteomyelitis. When the patients were divided into three groups according to the location of the infection, our study results showed a sensitivity and specificity for the central location (containing active bone marrow) of 94% and 100% respectively; for the peripheral location (hands and feet) both parameters were 100%, and for the middle location (all sites between the central and the peripheral location) the values were 92% and 81% respectively. Specificity and accuracy were significantly lower in the middle location than in the central and peripheral locations. The results of our study confirm that a^99mTc-d,l-HMPAO labelled leucocyte scan in combination with an^99mTc-MDP bone scan is a reliable way to diagnose chronic osteomyelitis, except for vertebral osteomyelitis.     

Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy

Pelvic inflammatory disease (PID) is one of the major health problems of women of child-bearing age. Among the most serious complications of PID is the formation of a tubo-ovarian abscess (TOA). Early diagnosis of this condition may prevent serious surgical complications such as peritonitis and sepsis, which may be fatal. The purpose of this study was to investigate the efficacy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in the diagnosis of TOA. Twenty women with high clinical suspicion of TOA underwent ^99mTc-HMPAO leucocyte scintigraphy. The labelling of leucocytes with ^99mTc-HMPAO was performed according to a standard protocol. Scans were obtained at 1, 3 and 24 h following the injection of the labelled leucocytes. In eight cases the early and/or late scan was positive, in 11 cases it was negative, and in one case of ovarian cyst torsion, confirmed by laparoscopy, it showed slight uptake in the capsule of the cyst (false-positive). The sensitivity of ^99mTc-HMPAO leucocyte scintigraphy was 100%, specificity 91.6%, positive predictive value 89%, negative predictive value 100% and overall accuracy 95%. It is concluded that leucocyte scintigraphy is a non-invasive, safe, physiological and accurate procedure for the diagnosis of TOA. The 24-h scan is crucial, since in some cases the abscess was not clearly visualized on the early scan. Leucocyte scintigraphy may reduce the need for CT, diagnostic laparoscopy and unnecessary invasive surgical procedures.     

Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy

Pelvic inflammatory disease (PID) is one of the major health problems of women of child-bearing age. Among the most serious complications of PID is the formation of a tubo-ovarian abscess (TOA). Early diagnosis of this condition may prevent serious surgical complications such as peritonitis and sepsis, which may be fatal. The purpose of this study was to investigate the efficacy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in the diagnosis of TOA. Twenty women with high clinical suspicion of TOA underwent 99mTc-HMPAO leucocyte scintigraphy. The labelling of leucocytes with 99mTc-HMPAO was performed according to a standard protocol. Scans were obtained at 1, 3 and 24 h following the injection of the labelled leucocytes. In eight cases the early and/or late scan was positive, in 11 cases it was negative, and in one case of ovarian cyst torsion, confirmed by laparoscopy, it showed slight uptake in the capsule of the cyst (false-positive). The sensitivity of 99mTc-HMPAO leucocyte scintigraphy was 100%, specificity 91.6%, positive predictive value 89%, negative predictive value 100% and overall accuracy 95%. It is concluded that leucocyte scintigraphy is a non-invasive, safe, physiological and accurate procedure for the diagnosis of TOA. The 24-h scan is crucial, since in some cases the abscess was not clearly visualized on the early scan. Leucocyte scintigraphy may reduce the need for CT, diagnostic laparoscopy and unnecessary invasive surgical procedures.     

Technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy in the early course of mild acute pancreatitis following endoscopic retrograde cholangiopancreatography

We evaluated the diagnostic accuracy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in mild acute pancreatitis. A study design was chosen that gave us an opportunity to assess patients by leucocyte scintigraphy in the very early course of the disease. Thirty-two consecutive patients referred for endoscopic retrograde cholangiopancreatography were followed according to a very rigid protocol with laboratory tests and clinical examination before and after the endoscopic procedure and leucocyte scintigraphy [including single-photon emission tomography (SPET)] performed within 24 h. Planar and SPET images were examined by two observers who were blinded to each other and to the clinical history and diagnosis. Eight (25%) of the 32 patients developed mild acute pancreatitis, and only one of these patients had a positive scan. Sensitivity, specificity and accuracy of 13%, 79% and 63%, respectively, were achieved when both planar and SPET images were considered. When only planar images were considered the sensitivity, specificity and accuracy were 13%, 96% and 75%, respectively. No evidence of pathological leucocyte accumulation in mild acute pancreatitis was found despite the aforementioned very rigid protocol, allowing patients to be assessed by^99mTc-HMPAO leucocyte scintigraphy in the very early phase of the disease (this was true even when using SPET). From a clinical point of view, we believe that leucocyte scintigraphy should be used only when the disease is moderate or severe and serious intra-abdominal complications are suspected.     

Three-phase white blood cell scan: diagnostic validity in abdominal inflammatory diseases

Indium-111-oxine saline-labeled "mixed" leukocyte (n = 16) and "pure" granulocyte (n = 66) scans were prospectively performed as "three-phase" white blood cell (WBC) scans (imaging: 30 min, 4 hr, and 24 hr after reinjection of the cells) in 82 patients suspected of having abdominal or retroperitoneal abscesses or inflammatory lesions. Inflammation was verified histologically, endoscopically, radiologically or by autopsy in 51 and excluded in 31 patients. Sensitivity, specificity, and diagnostic accuracy of the 30-min scan (90%, 56%, 72%) were statistically significantly lower than the 4-hr scan (96%, 97%, 98%). Of the 24-hr scan sensitivity, specificity, and diagnostic accuracy were only 84%, 98%, and 89% because many patients with chronic inflammatory bowel diseases had excreted a portion of intestinal 111In activity by 24 hr. The overall sensitivity, specificity, and accuracy of the "three-phase" WBC scan were 98%, 97%, and 98%, respectively. Only one female patient showed a false-positive scan with granulocyte uptake in an ulcerating adenocarcinoma of the colon. The 4-hr scan or the three-phase study are recommended because of their high sensitivity, specificity, and excellent diagnostic accuracy (98%). The 30-min scan is less specific (56%); the 24-hr scan less sensitive (84%). The three-phase study additionally allows the differentiation between inflammatory bowel diseases and abscesses because it allows observation of granulocyte kinetics for 24 hr.     

The development of a clinical protocol for the radiolabelling of mixed leucocytes with 99Tcm-hexamethylpropyleneamine oxime

To devise a protocol for the radiolabelling of mixed leucocytes with 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO), the effect of HMPAO concentration, cell concentration, plasma concentration and anticoagulant on the uptake of the lipophilic complex was measured, together with the stability of the 99Tcm on the labelled cells. It was found that cell uptake was rapid, independent of HMPAO concentration over the range 20-80 micrograms ml-1, but dependent on cell and plasma concentration. Incubation of mixed leucocytes from 85 ml blood with 1 ml ACD-plasma and 4 ml 99Tcm-HMPAO containing 400 MBq 99Tcm for 10 min at room temperature gave optimum results and was used in 90 patients. The mean labelling efficiency, which was the amount of added 99Tcm incorporated by the cells, was 55% (+/- 13 S.D.), of which 77% were incorporated by the granulocytes, 17% by the mononuclear cells and 6% by the platelets and erythrocytes. During a 1 h incubation in plasma 9% (+/- 4% S.D.) of the 99Tcm were released from the labelled mixed leucocytes. This occurred predominantly from the mononuclear cells.     

Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic accuracy in the detection of hip replacement infections

Although the diagnosis of hip prosthesis infection is clinically important, X-ray studies, blood chemistry and synovial fluid aspiration may be unreliable for this purpose. The aim of this study was to evaluate whether extending the time for technetium-99m labelled leucocyte imaging to 24 h post injection improves the accuracy of diagnosis of hip replacement infections. We studied 64 symptomatic patients with hip prostheses. The presence of infections was verified by intraoperative bacterial cultures, and infection was excluded either by negative operative findings or by follow-up for at least 1 year. Leucocyte imaging was done with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocytes at 2-4 h (routine images) and at 24 h (late images) after the injection of the leucocytes. In addition, bone imaging was carried out with 99mTc-hydroxydiphosphonate (HDP) at the arterial, soft tissue and metabolic phases. A standardised method was used to compare leucocyte images with bone metabolic images. In this material, there were six confirmed infections. All the bone imaging methods had a sensitivity of 100% in detecting prosthesis infections whereas the specificity varied from only 2% to 82%. Routine leucocyte imaging was less sensitive (50% vs 83%) and less specific (90% vs 100%) than late leucocyte imaging. All tests had a high negative predictive value for excluding infection (95%-100%). However, both bone (10%-38%) and routine leucocyte imaging (33%) showed a poor positive predictive value (PPV), whereas late leucocyte imaging had a PPV of 100% and a diagnostic accuracy of 98%. We conclude that late leucocyte imaging improves the specificity of diagnosis of infected hip prostheses. This type of imaging procedure should be combined with three-phase bone scintigraphy in studies of patients with painful joint replacement.