Biological consequences of the heterogeneous irradiation of lymphocytes during technetium-99m hexamethylpropylene amine oxime white blood cell labelling

Technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) labelling of white blood cells, routinely used for the detection of infection, results in the incorporation of radioactivity by polymorphonuclear leucocytes and also lymphocytes and can induce cell lesions in the latter case. The aim of this study was therefore to acquire data on the morphological and functional status of labelled lymphocytes present in the ^99mTc-HMPAO leucocyte mixture and to determine the cellular consequences of labelling. The mean radioactivity associated with lymphocytes was 325±10.8 kBq/10⁶ lymphocytes under standard labelling conditions. Microautoradiographic studies showed that labelling was heterogeneous (4% intensely labelled cells), which prevented calculation of the mean absorbed dose. The frequency of chromosomal aberrations (dicentrics and rings) in the labelled lymphocytes for 380 kBq/10⁶ cells was 1.08±0.09 but no abnormality was observed in the unlabelled control lymphocytes. The plating efficiency of labelled lymphocytes was reduced, as compared with that for control cells, but some lymphocytes were still able to form clones and were still ”alive” by radiobiological definition. It is therefore suggested that lymphocytes should be removed from ^99mTc-HMPAO cell preparations before administration to patients. Received 9 March and in revised form 1 June 1998     

Labelling of leucocytes with technetium-99m exametazime causes in vitro upregulation of granulocyte CD11b without correlation to tissue uptake in vivo

The aims of this study were to investigate whether labelling with technetium-99m exametazime alters the expression of adhesion molecule CD11b on granulocytes and monocytes, and to study whether the expression of CD11b on unlabelled or labelled cells correlates with uptake of the labelled cells in the inflamed bowel, in the lungs or in the reticuloendothelial system. Leucocytes were obtained from 25 patients with inflammatory bowel disease who underwent leucocyte scan. The cellular expression of CD11b was analysed using flow cytometry. Labelling with^99mTc-exametazime induced an increased surface expression of CD11b on granulocytes (P<0.01), but not on monocytes. The increase in CD11b expression on granulocytes was lower than the spontaneous mobilization that occurred at 37° C and correlated neither with this, nor withN-formyl-methionyl-phenylalanine induced expression of the same receptor. Basal expression of CD11b on unlabelled granulocytes, but not on monocytes, correlated with bowel and lung uptake 45 min after reinjection of labelled cells, but not with uptake on later images. No correlation was found between the CD11b expression on labelled granulocytes or monocytes and scintigraphic uptake. Our findings show that labelling with^99mTc-exametazime increases the expression of adhesion protein CD11b on granulocytes. The increase in surface expression of CD11b does not correlate with the scintigraphic uptake of labelled cells in the bowel, in the lungs or in the reticuloendothelial system.     

Measurement of the secretion of technetium-99m hexamethylpropylene amine oxime into breast milk

There are no published data for the activity of technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) found 1in breast milk. The amount of radioactivity in breast milk following the administration of 500 MBq^99mTc-HMPAO for a brain perfusion study has been measured. The effective dose to the infant was calculated to be 0.26 mSv, so necessitating no interruption of breast feeding. Unbound^99mTc is readily secreted into breast milk and the effective dose will remain less than 1 mSv if the^99mTc-HMPAO labelling effici ency is 99% for the worse reported case, and could remain <1 mSv for the mean reported case for^99mTc-HMPAO labelling efficiencies down to 94%.     

Tc-99m-HMPAO labelled human platelets: in vitro and in vivo results

The lipophilic ^99mTc-HMPAO complex can be used for labelling platelets as well as granulocytes. Platelets were isolated according to standard isolation procedures for the evaluation of the optimal labelling parameters. The labelling efficiency (%) depends on incubation temperature (22° C: 40%; 37° C: 50%), incubation time (3 min: 20%, 25 min: 55%) and the incubation medium (plasma: 40%; saline 50%). The 60 min ^99mTc elution, out of the platelets ranged around 8%. The platelet recovery used as a quality control parameter is around 25%±4% and is stable for at least 240 min. The high elution rate out of the platelets leads to renal excretion of the label and hence to significant kidney and bladder activity. Intestinal excretion of the label can also be frequently demonstrated. Fresh thrombotic lesions can normally be detected 4 h after reinjection of the labelled platelets, and in some patients as early as 1 h after reinjection. In conclusion, ^99mTc-HMPAO seems to be a promising platelet label for imaging thrombotic lesions but not for platelet survival studies, because of the short physical half life of ^99mTc.Supported by the Deutsche Forschungsgemeinschaft (BE 1054/1–2)     

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. Received 9 November 1998 and in revised form 1 February 1999     

Technetium-99m and indium-111 double labelling of granulocytes for kinetic and clinical studies

A new technique of labelling granulocytes with both technetium-99m hexamethylpropylene amine oxime (HMPAO) and indium-111 in a single protocol was developed in order to exploit the advantages of each radiolabel in clinical and investigative studies. Fourteen patients were included in this prospective study. Granulocytes were labelled with both¹¹¹In-tropolonate and^99mTc-HMPAO. In vitro shape change assay and in vivo distribution and recovery studies were performed to assess the activation of and damage to these cells due to the labelling procedure. The comparative kinetics of¹¹¹In and^99mTc in the blood, liver, spleen, and bone marrow were studied by blood sampling and dual radionuclide imaging early (1 h) and late (24 h) after injection. The functional integrity of the double-labelled granulocytes and the feasibility of the technique were investigated in 14 patients with a painful prosthetic hip due to causes other than infection. The efficiency of double labelling was 63% (SD 14%) for¹¹¹In and 39% (SD 12%) for^99mTc-HMPAO. In vitro granulocyte activation and ex vivo recovery values were comparable to those from single radionuclide labelling. No artefactual granulocyte sequestration was seen in the lungs or liver. The radioactivity was distributed between the liver, spleen and bone marrow and, to a lesser extent, the lung. Early^99mTc counts in the liver, spleen and bone marrow, in relation to background, were significantly higher than¹¹¹In counts while the reverse was seen in late images. Furthermore, circulating free^99mTc was significantly higher than free¹¹¹In at 24 h. Organ^99mTc counts, expressed in relation to the activity in early images, decreased in the spleen, increased in the liver and remained unchanged in bone marrow, whereas¹¹¹In counts increased in the bone marrow and liver, and decreased in the spleen. Granulocytes can be labelled with both¹¹¹In and^99mTc-HMPAO in a single protocol without crosschelation, cellular activation or damage. By favourably exploiting their kinetics for early and late imaging, double-labelled granulocytes may be useful in several clinical and investigative situations.     

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.     

Uptake of technetium-99m hexamethylpropylene amine oxime labelled white cells in lymph nodes involved in non-Hodgkin's lymphoma

Radiolabelled white cell scanning is widely used to detect the presence of infection. We present a case of non-Hodgkin's lymphoma manifesting with signs and symptoms suggestive of infection, in which a technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) white cell scan demonstrated high uptake in lymph nodes involved by lymphoma. Differential cell analysis showed preferential lymphocyte labelling. The classification and management of the disease were changed accordingly. Our findings suggest that a future role for^99mTc-HMPAO labelled white cells in the assessment of disease activity of lymphoma should be investigated.     

The behavior of99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain

^99mTc-hexamethylpropyleneamineoxime (^99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how^99mTc-HMPAO changed in the blood and brain. The^99mTc-HMPAO, which was prepared by adding of^99mTcO _- ⁴ to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed^99mTc, and^99mTc0pertechnetate. The percentage of the primary complex in^99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When^99mTc-HMPAO was injected into patients,^99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma,^99mTc was found to be associated with proteins such as albumin and globulin.^99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of^99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific^99mTc binding protein was present in the brain. Considering the instability of^99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing^99mTc-HMPAO to pass through the BBB and to be fixed in the brain.     

Media Fill Test for validation of autologous leukocytes separation and labelling by 99mTc-HmPAO

ObjectiveManufacturing of sterile products must be carried out in order to minimize risks of microbiological contamination. White blood cells (WBC) labelled with ^99mTc-exametazime (^99mTc-hexamethylpropyleneamine oxime; ^99mTc-HMPAO) are being successfully applied in the field of infection/inflammation scintigraphy for many years. In our radiopharmacy lab, separation and labelling of autologous leukocytes with ^99mTc-HMPAO were performed in a laminar flow cabinet not classified and placed in a controlled area, whereas ^99mTc-HMPAO radiolabelling procedure was carried out in a hot cell with manipulator gloves. This study was conducted to validate this process using a Media Fill simulation test.MethodsThe study was performed using sterile Tryptic Soy Broth (TSB) in place of active product, reproducing as closely as possible the routine aseptic production process with all the critical steps, as described in the our internal standard operative procedures (SOP). The final vials containing the media of each processed step were then incubated for 14 days and examined for the evidence of microbial growth.ResultsNo evidence of turbidity was observed in all the steps assayed by the Media Fill.ConclusionsIn the separation and labelling of autologous leukocytes with ^99mTc-HmPAO, Media-Fill test represents a reliable tool to validate the aseptic process.     

“Luxury perfusion” with99mTc-HMPAO and123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of¹²³I-isopropyl-iodoam-phetamine (¹²³I-IMP) and^99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with¹²³I-IMP and^99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal^99mTc-HMPAO SPECT and abnormal¹²³I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on^99mTc-HMPAO in areas corresponding to defects on the¹²³I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination,^99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on¹²³I-IMP. Crossed cerebellar diaschisis was found in 7 patients with^99mTc-HMPAO and was absent for both¹²³I-IMP and^99mTc-HMPAO in 3. We suggest that SPECT with⁹⁹mTc-HMPAO could show transient hyperemia not demonstrated by¹²³I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with^99mTc-HMPAO than with¹²³I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.     

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     

Guidelines for the labelling of leucocytes with 99mTc-HMPAO

We describe here a protocol for labelling autologous white blood cells with ^99mTc-HMPAO based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations.     

Evaluation of technetium 99m cyclobutylpropylene amine oxime as a potential brain perfusion imaging agent for SPET

Technetium 99md,l-cyclobutylpropylene amine oxime (^99mTc-CBPAO) has been developed as a brain-imaging agent for single photon emission tomography (SPET).^99mTc-CBPAO can be prepared using a simple labelling procedure suitable for routine clinical use. It has a high in vitro stability, as has been demonstrated by high-pressure liquid chromatography (HPLC) analysis. This shows that 3 h after labelling, less than 5% of the primary lipophilic complex which is capable of crossing the blood-brain barrier (BBB) converts to a secondary hydrophilic complex. Brain uptake (% dose/g wet tissue) of^99mTc-CBPAO, determined at 5 and 30 min after injection in two groups of six adult male Sprague-Dawley rats, was found to be 0.74±0.06 and 0.73±0.13 (mean ± SD), respectively. These values are not significantly different from those obtained repeating the experiment with^99mTc-labelled hexamethylpropylene amine oxime (^99mTc-HMPAO) (0.72±0.15 at 5 min and 0.88 ± 0.24 at 30 min after injection). Since the rat brain uptake of^99mTc-CBPAO remained unchanged for a period of time suitable for tomographic study, the comparison of the two tracers was extended to two groups of ten patients. The latter were affected by neurological and psychiatric disorders and were studied with SPET. Human brain uptake (% dose/cc cortical grey matter) of^99mTc-CBPAO and^99mTc-HMPAO were 3.04±0.57 and 4.22±0.46 (mean × 10^–3 ± SD × 10^–3), respectively, with a 32% significant difference. In two other groups of five patients, the first transit time-activity curves of the two tracers were compared. From the analysis of these curves we suggest that^99mTc-CBPAO has a higher binding effect on blood components and/or a higher degradation rate in blood than that of^99mTc-HMPAO. This may account for the reduced human brain uptake. In conclusion, SPET images of^99mTc-CBPAO reflect blood perfusion, and they have a good diagnostic quality. The main advantage of^99mTc-CBPAO is its in vitro stability; however,^99mTc-HMPAO is a superior imaging agent.     

In vitro assessment of cytotoxicity and labeling efficiency of 99mTc-HMPAO with stromal vascular fraction of adipose tissue

IntroductionNoninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime (^99mTc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of ^99mTc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy.MethodsTen million cells of SVF were labeled with ^99mTc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of ^99mTc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H₂DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1.ResultsAn encouraging labeling efficiency of 33% was observed with ^99mTc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays.Conclusion^99mTc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with ^99mTc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy.     

Comparison of simultaneous 99mTc-HMPAO and 111In oxine labelled white cell scans in the assessment of inflammatory bowel disease

Forty-seven patients, 29 with chronic inflammatory bowel disease (1131) and 18 with presumed irritable bowel syndrome, including one with uncomplicated diverticular disease, were studied with simultaneous technetium-99m hexamethylpropylene amine oxime and indium-111 oxine labelled leucocyte scans performed at 1, 3 and 24 h. Twenty-seven patients with IBD had active disease as judged by clinical and laboratory criteria and all of these had positive scans with both agents. No false positive studies were obtained. The 1-h ^99mTc-HMPAO WBC scans showed the same distribution to disease as the 3-h ¹¹¹-In WBC scans, with no difference in intensity (P < 0.92); they showed more extensive disease (P < 0.02) and more intense uptake (P < 0.001) than did the 1-h ¹¹¹-In scans. The 3-h ^99mTc-HMPAO WBC scans showed more extensive disease (P < 0.002), with greater intensity (P < 0.0005), than did the 3-h ¹¹¹In WBC scans. Physiological bowel activity on 3-h ^99mTc-HMPAO WBC scans was present in 12 patients but was faint and did not interfere with assessment of disease extent and activity. It is concluded that in terms of isotope availability, radiation dosimetry and image quality, ^99mTc-HMPAO is the agent of choice in detecting active IBD, with localization of disease possible at 1-h after re-injection and optimal resolution and definition of disease extent at 3 h. A negative scan reliably excludes active disease. Correspondence to: R.A. Allan     

An evaluation of99mTc-HMPAO uptake in cerebral gliomas —a comparison with X-ray CT

Nineteen patients with biopsy-proven cerebral gliomas were studied with^99mTc-HMPAO single photon emission tomography (SPELT) imaging and X-ray computed tomography (CT). The uptake of^99mTc-HMPAO was correlated with tumour size and morphology as shown by X-ray CT, and overall patient survival. It appears that uptake of^99mTc-HMPAO is associated with larger, ill-defined tumours and was an adverse factor in patient survival. In those tumours with normal or increased uptake,^99mTc-HMPAO imaging is useful in distinguishing the tumour margin from surrounding oedema.     

Contribution of technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy to the diagnosis of diabetic foot infection

We conducted a prospective study in order to evaluate the contribution of technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled leucocyte scintigraphy to the diagnosis and follow-up of osteomyelitis in the diabetic foot. The study was conducted between October 1992 and November 1996 and included 42 patients (30 men and 12 women; mean age 63 years) with diabetes mellitus (type 1, n = 22, type 2, n = 20) who had a total of 56 diabetic foot ulcers. The initial exploration included standard radiography, three-phase bone scintigraphy and ^99mTc-HMPAO labelled leucocyte scintigraphy (HMPAO-LS), performed within a 3-day interval. For the 56 ulceration sites, 26 cases of osteomyelitis were diagnosed: ten on the basis of radiographic and histological/bacteriological criteria after bone biopsy, 11 after radiographic follow-up and five on the basis of biopsy results alone. No osteomyelitis was present at 30 sites, there were seven cases of cellulitis. The sensitivity and specificity of ^99mTc-HMPAO-LS were 88.4% and 96.6% respectively (23 true-positives, 29 true-negatives, one false-positive, three false-negatives). The accuracy of radiography, ^99mTc-methylene diphosphonate and HMPAO-LS was 69.6%, 62.5%, and 92.9%, respectively. Follow-up scintigraphy (n = 14) 4 months after initial diagnosis and 1 month after antibiotic withdrawal confirmed cure of osteomyelitis despite the absence of complete clinical regression of the ulcers. In conclusion, ^99mTc-HMPAO labelled leucocyte scintigraphy was found to be an excellent method for the diagnosis of osteomyelitis in the diabetic foot. It can contribute to follow-up, particularly when clinical regression of perforating ulcers is incomplete and cure of osteomyelitis must be confirmed in order that antibiotic treatment may be discontinued. Received 10 July and in revised form 1 October 1997     

Sternal wound infection revisited

Sternal wound infections (SWIs) can be subdivided into two types, superficial or deep, that require different treatments. The clinical diagnosis of superficial SWI is normally easy to perform, whereas the involvement of deep tissues is frequently difficult to detect. Therefore, there is a need for an imaging study that permits the assessment of SWIs and is able to distinguish between superficial and deep SWI. The present work was a prospective study aiming to evaluate the role of technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) labelled leucocyte scan in SWI management. Twenty-eight patients with suspected SWIs were included in the study. On the basis of clinical examination they were subdivided into three groups: patients with signs of superficial SWI (group 1), patients with signs of superficial SWI and suspected deep infection (group 2) and patients with suspected deep SWI without superficial involvement (group 3). Ten patients previously submitted to median sternotomy, but without suspected SWI, were also included in the study as a control group (group 4). All patients with suspected SWI had bacteriological examinations of wound secretion, if present. In addition ^99mTc-HMPAO labelled leucocyte scan was performed in all patients. The patients of groups 1, 2 and 3 were treated on the basis of the clinical signs and microbiological findings, independently of the scintigraphic results. The patients of group 4 did not receive treatment. The final assessment of infection was based on histological and microbiological findings or on long-term clinical follow-up. Sensitivity, specificity, accuracy and positive and negative predictive values for scintigraphic and non-scintigraphic results were calculated. In the diagnosis of superficial and deep SWI, clinical and microbiological examination (combined) yielded, respectively, a sensitivity of 68.7% and 100%, a specificity of 77.3% and 80.8%, an accuracy of 73.7% and 86.8%, a positive predictive value of 68.7% and 70.6% and a negative predictive value of 77.3% and 100%. The scintigraphic results obtained in superficial SWI yielded a sensitivity of 56.2%, a specificity of 90.9%, an accuracy of 76.3%, a positive predictive value of 81.8% and a negative predictive value of 74.1%, while, by contrast, in deep SWI all of these values were 100%. Therefore, one can conclude that ^99mTc-HMPAO labelled leucocyte scan permits accurate diagnosis of deep SWI, solving the main clinical problem in this field. In the present study the categorisation of patients without taking into account ^99mTc-HMPAO labelled leucocyte planar scan findings caused a non-negligible number of cases of superficial SWI to be treated as though they were deep SWI. This ”overestimation” led to unnecessary surgery, increased and prolonged use of antibiotics with more (higher) toxicity and additional expense. Received 6 December 1999 and in revised form 5 February 2000     

In vivo metabolism and kinetics of99mTc-HMPAO

The cerebral distribution of^99mTc-labeled d, l, hexamethyl-propylene-amine-oxime (^99mTc-HMPAO) as a function of rCBF and time was examined in rats and in man. The results of this study confirm that^99mTc-HMPAO is distributed in brain in proportion to rCBF. However, the rapid systemic breakdown of the tracer in blood results in considerable difficulties in the assessment of the arterial concentration of the parent compound; incomplete extraction of^99mTc-HMPAO from blood to brain and significant efflux from brain represent further limitations in the use of this tracer for quantification of rCFB. Despite these limitations^99mTc-HMPAO is of potential interest for a qualitative assessment of rCBF in specific clinical conditions.