Technetium-99m hexamethyl propylene amine oxine leucocytes in the assessment of disease activity in inflammatory bowel disease

The inflammatory activity in 108 bowel segments of 40 patients with suspected or known inflammatory bowel disease was assessed macroscopically by endoscopy, histology and technetium-99m hexamethyl propylene amine oxine (^99mTc-HMPAO) leucocytes using a numerical grading system (scores 0–3). A 4-h series of scintigrams showed a significant correlation with both histological and macroscopical assessment of disease activity (rho = 0.850, P<0.001 and rho = 0.773, P<0.001, respectively). Sensitivity, specificity and accuracy of scintigraphy in detecting active inflammatory segments were 85%, 92% and 89%, respectively. A normal scintigram did not completely exclude mild inflammatory activity, especially in the rectosigmoid area. ^99mTc-HMPAO leucocytes offer an accurate and non-invasive alternative for the assessment of disease activity in ulcerative colitis and Crohn's disease. Offprint requests to: E. Lantto     

The use of technetium-99m hexamethylpropylene amine oxime labelled white blood cells to detect subclinical inflammation of the heart after cardiopulmonary bypass in children with congenital heart disease

Ten children (6 boys and 4 girls, aged 1–9 years old) underwent operations with a cardiopulmonary bypass, and the technetium-99m hexamethylpropylene amine oxine (^99mTc-HMPAO) labelled white blood cell (WBC) heart scans were used to detect postoperative leukocyte infiltration in the hearts. The results showed that 80% (/810) of the cases had subclinical inflammation in the hearts (grading of WBC scans score 2), and a positive correlation (R = 0.77) was noted between the severity of the inflammation (grading of the WBC scans) and the duration of the cardiopulmonary bypass in the operations. Another control group (9 boys and 2 girls, aged 2–13 years old) underwent operations without a cardiopulmonary bypass, and subclinical inflammation of hearts was demonstrated in only 1 case (9%) by the ^99mTc-HMPAO labelled WBC scans (grading of WBC scans < score 2) after the operations. There was a significant difference (P < 0.001, by a Wilcoxon rank sum test) based upon the severity of the ischaemic heart damage in the two groups. In our preliminary conclusions, the ^99mTc-HMPAO labelled WBC heart scans may provide non-invasive and directly discernible evidence of subclinical inflammation in the heart due to a transient ischaemic state during a cardiopulmonary bypass, even if the clinical symptoms and signs of carditis are not apparent. Correspondence to: Chia-Hung Kao     

Pethidine-augmented white cell scintigraphy in inflammatory bowel disease

Technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) white cell scintigraphy is invaluable for assessing the presence and extent of disease activity in patients with inflammatory bowel disease. Interpretation of images can be compromised by physiological excretion of tracer into the bowel via the biliary tree. This study assesses the effect of intravenous pethidine administered with the labelled white cells in an attempt to reduce the enterohepatic circulation of the tracer. Ninety-one subjects with proven or suspected inflammatory bowel disease were included in this study, all of whom underwent ^99mTc-HMPAO white cell scintigraphy. The control group of 50 subjects underwent the standard protocol for this study performed in our department. The other 41 subjects received an intravenous injection of 0.3 mg/kg of pethidine at the same time as re-injection of the labelled white cells. Images were graded using a five-point scale at both 1 and 2.5 h and categorised as positive, negative or non-diagnostic. Each scan was also assessed for the presence of a visible gall-bladder. The pethidine group had significantly fewer non-diagnostic scans than the control group (P=0.003), and significantly (P=0.001) more studies in which the gall-bladder was visualised. It is concluded that the use of pethidine appears to reduce biliary excretion of tracer during ^99mTc-HMPAO white cell scintigraphy. This may allow the delayed images, and early images with low-grade tracer uptake in the bowel, to be interpreted with greater confidence and thereby reduce the number of scans classified as non-diagnostic. Received 14 December 1999 and in revised form 16 February 2000     

Abdominal scintigraphy using99mTc-HMPAO-labelled leucocytes in patients with seronegative spondylarthropathies without clinical evidence of inflammatory bowel disease

Abdominal scintigraphy with technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO)-labelled leucocytes is an excellent tool for evaluating disease extent and activity of intestinal lesions in patients with inflammatory bowel disease (IBD). In some cases of seronegative spondylarthropathies (SSp), IBD may remain subclinical. The aim of this study was to evaluate the presence of positive abdominal scintigraphy in patients with SSp and without clinical symptoms or signs of IBD. To this end we studied 32 patients with active SSp (European Spondylarthropathy Study Group 1991 criteria) without clinical evidence of IBD (eight had ankylosing spondylitis, four psoriatic arthritis, three reactive arthritis an 17 undifferentiated SSp) and 11 controls without SSp. All SSp and control patients received similar doses of non-steroidal anti-inflammatory drugs (NSAIDs). Abdominal scintigraphic images were obtained at 30 and 120 min after re-injection of^99mTc-HMPAO-labelled leucocytes. The^99mTc-HMPAO-labelled leucocyte scan was positive in 17 patients with SSp (53.1%) (six with ankylosing spondylitis, three with psoriatic arthritis, two with reactive arthritis and six with undifferentiated SSp). Fourteen patients scored from 2 to 4 on the intensity of uptake scale. The colon and terminal ileum were predominantly involved. Axial involvement was more frequent in patients with a positive scan than in patients with negative results (P<0.05) (64.7% vs 26.6%; odds ratio: 5). No control patient showed a positive scan. It is concluded that^99mTc-HMPAO-labelled leucocyte scan shows increased uptake among patients with SSp without evidence of IBD. These findings provide new evidence linking SSp with intestinal inflammation and suggest that in some cases a bowel-related process could contribute to the development of SSp. Longterm follow-up studies with more patients are necessary to evaluate the diagnostic and therapeutic implications of these results.     

Intraindividual comparison of 99mTc-labelled anti-SSEA-1 antigranulocyte antibody and 99mTc-HMPAO labelled white blood cells for the imaging of infection

Technetium-99m labelled antigranulocyte antibodies are ready to use and are sensitive and specific in the diagnosis of infectious diseases. ^99mTc-SSEA antigranulocyte antibodies have a very high affinity constant (K _d 10^–12 M) for human neutrophils (PMNs), and excellent imaging qualities with high target/background ratios. The aim of this study was to compare the diagnostic accuracy of the ^99mTc-anti-SSEA-1 monoclonal antibody (Mab) with that of ^99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled white blood cells (WBCs). To this end, 17 patients with 23 proven infectious foci were examined with 555 MBq ^99mTc-anti-SSEA-1 MAb and with 370 MBq ^99mTc-HMPAO labelled autologous leucocytes within a period of 7 days. All the infections were confirmed by culture, biopsy, surgery and follow-up. Whole-body images and planar spot views with the antibody were performed at 1-h, 4-h and 24-h post injection; the biodistribution of the antibody was quantified, absorbed radiation doses were calculated and the diagnostic results were compared with the ^99mTc-HMPAO WBC images. Human anti-mouse antibody (HAMA) evaluation was performed in all patients before and 3 months after antibody injection. Blood was drawn at different times after ^99mTc-anti-SSEA-1 MAb injection to determine the amount of granulocyte-associated radioactivity and to calculate recovery. ^99mTc-anti-SSEA-1 MAb scintigraphy detected all 23 lesions, while 21 were detected with ^99mTc-HMPAO WBC scan. In this small group of patients, the sensitivity and specificity of ^99mTc-anti-SSEA-1 MAb scintigraphy were 95% and 96% respectively, as compared with 91% and 82% respectively for ^99mTc-HMPAO WBC scan. An increasing uptake of the injected activity in the lesion at different time points was indicative of high affinity and of specific PMN binding.There was no HAMA formation. In four of five patients investigated, a transient mild leukopenia was found at 15 min p.i.. There was increased uptake of the antibody in liver and spleen and normal uptake in kidneys and bone marrow.The estimated radiation doses for the whole body and the red bone marrow were 1.1×10^–2 cGy/37 MBq and 5.3×10^–2 cGy/37 MBq, respectively. The activity associated to the PMNs in vivo was 33.5%, 30.6%, 21.3% and 9% at 5, 15, 30 and 45 min. post-injection, respectively. It is councluded that use of ^99mTc-anti-SSEA-1 antigranulocyte antibodies demonstrates promising results comparable to those obtained with ^99mTc-labelled autologous WBCs. The ^99mTc-labelled MAb is ready to use, has excellent image qualities and a high target/background ratio. Received 16 October and in revised form 17 December 1997     

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.     

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.     

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     

A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO)

Although specific patterns of technetium-99m exametazime [^99mTc-hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi-institutional study has evaluated interobserver agreement. Interobserver agreement for ^99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n=21), confirmed Alzheimers's disease (n=10), multi-infarct dementia (n=9), HIV-related dementia (n=7), or mixed (n=3). In addition 20 normal (five per institution) ^99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated ^99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers.Subject studies performed at St. Vincent's Hospital, New York     

Quantification of disease activity in patients undergoing leucocyte scintigraphy for suspected inflammatory bowel disease

Purpose Whole-body gamma camera counting is an alternative to faecal ¹¹¹In collection for quantifying disease activity in inflammatory bowel disease (IBD) but requires administration of imaging activities of ¹¹¹In. The aim of this study was to explore a dedicated whole-body counter which requires 20-fold less activity than gamma camera counting.Methods Thirty patients with known or suspected IBD received ^99mTc-granulocytes (200 MBq) and ¹¹¹In-granulocytes (0.5 MBq). The ^99mTc-cells were injected 45 min after the ¹¹¹In-cells and immediately after a baseline ¹¹¹In whole-body count. The decay-corrected count at 120 h was expressed as a fraction of baseline to give whole-body ¹¹¹In retention (WBR). One patient was excluded as the injected cells were non-viable.Results Median 45-min intravascular ¹¹¹In recovery was 35% in patients compared with 43% in six normal volunteers (p<0.05). WBR in normals ranged from 91% to 93% and in 11 patients with negative ^99mTc imaging from 87% to 96%. Only one of 11 patients with negative imaging had WBR <90% while 11/12 patients with WBR <90% had abnormal imaging. Ten of 13 patients with Crohns disease (CD) had abnormal imaging. The lowest WBR in these ten was 77% and six had values of >90%. There was a significant association between WBR and ^99mTc image grade (R_s=0.73, p<0.002) in 16 patients without CD, but not in 13 patients with CD (R_s=0.54, p>0.05).Conclusion Dedicated whole-body counting is able to quantify disease activity in IBD but may give normal values in active CD.     

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

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

A quantitative approach to technetium-99m ethyl cysteinate dimer: a comparison with technetium-99m hexamethylpropylene amine oxime

To develop non-invasive regional cerebral blood flow (rCBF) measurements using technetium-99m ethyl cysteinate dimer (^99mTc-ECD) and single-photon emission tomography (SPET), the same graphical analysis as was described in our previous reports using technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was applied to time-activity data for the aortic arch and brain hemispheres after intravenous injection of^99mTc-ECD. Hemispherical brain perfusion indices (BPI) for^99mTc-ECD showed a highly significant correlation (n = 22,r = 0.935,P = 0.0001) with those for^99mTc-HMPAO in 11 patients who underwent both tracer studies. Using both linear regression line equations between^99mTc-ECD BPI and^99mTc-HMPAO BPI and between^99mTc-HMPAO BPI and mean cerebral blood flow (CBF) values obtained from a xenon-133 inhalation SPET method in a previous study,^99mTc-ECD BPI was converted to¹³³Xe CBF values (y = 2.60x + 19.8). Then raw SPET images of^99mTc-ECD were converted to rCBF maps using Lassen's correction algorithm. In this algorithm, the correction factor a was fixed to 1.5, 2.6 and infinite. In the comparison of rCBF values for^99mTc-ECD SPET with those for^99mTc-HMPAO SPET in 396 regions of interest in the aforementioned 11 patients, the fixed correction factor of 2.6 gave nearly the same rCBF values for^99mTc-ECD (50.1 ± 16.9 ml/100 g/min, mean ± SD) as for^99mTc-HMPAO (49.9 ± 17.3 ml/100 g/min). In conclusion, the same non-invasive method as has been used in^99mTc-HMPAO studies is applicable to a^99mTc-ECD study for the measurement of rCBF without any blood sampling.     

An evaluation of 99mTc pertechnetate scanning for the detection of coeliac disease and Crohn's disease

To investigate the use of abdominal scintiscanning in the detection of small bowel pathology, the accumulation of pertechnetate (^99mTc), following intravenous injection, has been studied in 21 patients with coeliac disease, 13 patients with Crohn's disease and in 83 control subjects without known small bowel disease. Although a trend for a greater accumulation of ^99mTc was noted in patients with coeliac disease and Crohn's disease compared with controls (P(0.025) there was a large overlap in individual studies. Under the conditions of this study the accumulation of ^99mTc by the small bowel did not provide a reliable diagnostic test for coeliac disease or Crohn's disease of the small intestine. The accumulation of ^99mTc pertechnetate by normal small bowel suggests that scintiscanning with this radiopharmaceutical does not provide a consistently reliable method for the detection of small bowel pathology.     

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     

Evaluation of primary lung carcinoma using technetium 99m-hexamethylpropylene amine oxime: preliminary clinical experience

^99mTc-labelled hexamethylpropylene amine oxime (HMPAO) is a lipophilic compound with a neutral charge which reflects tumor blood flow and has been previously investigated to estimate brain blood flow. In this study, we attempted to use^99mTc-HMPAO for the evaluation of 18 patients with histologically proven primary lung carcinoma. The eight surgical specimens revealed that viable carcinoma cells were present when the^99mTc-HMPAO accumulated in the tumor, however, extensive tumor necrosis was observed when defective or ring like uptake was seen in the tumor. Qualitative study revealed that when perfusion defects were observed corresponding to the tumor, the possibility of squamous cell carcinoma or large cell carcinoma was high instead of adenocarcinoma. Quantitative analysis revealed that the uptake ratio was statistically different between adenocarcinoma (1.6±0.1) and squamous cell carcinoma (1.2±0.4) (P<0.05), between squamous cell carcinoma and large cell carcinoma (0.9±0.1) (P<0.05), and also between adenocarcinoma and large cell carcinoma (P<0.01). In conclusion,^99mTc-HMPAO may be useful for the evaluation of patients with primary lung carcinoma.     

An alternative approach to estimation of the brain perfusion index for measurement of cerebral blood flow using technetium-99m compounds

Cerebral blood flow (CBF) has been quantified non-invasively using the brain perfusion index (BPI) determined from radionuclide angiographic data generated by technetium-99m hexamethylpropylene amine oxime(^99mTc-HMPAO) or technetium-99m ethyl cysteinate dimer(^99mTc-ECD). The BPI is generally calculated using graphical analysis (GA). In the present study, BPI was measured using spectral analysis (SA), and its usefulness evaluated in comparison with GA. The BPI was calculated from the sum of spectral data obtained by SA. We applied this method to radionuclide angiographic data collected from the bilateral brain hemispheres of 20 patients with various brain diseases using ^99mTc-HMPAO and from those of 20 patients using ^99mTc-ECD. We also measured BPI using GA. The BPI values obtained by SA (BPI^S) (x) and by GA (BPI^G) (y) correlated closely (y=0.708x+0.038, r=0.945 for ^99mTc-HMPAO and y=0.559x+0.093, r=0.931 for ^99mTc-ECD). However, the BPI^G values were underestimated by 22.9%±6.6% (mean±SD) for ^99mTc-HMPAO and by 27.9%±7.5% for ^99mTc-ECD as compared with the BPI^S values. The extent of underestimation tended to increase with increasing BPI^S values. These findings were considered to be a result of the BPI^G values being affected by the first-pass extraction fraction of the tracer. We also compared the BPI^S and BPI^G values with those of CBF measured using N-isopropyl-p-[¹²³I]iodoamphetamine (CBF^IMP) in 16 patients (six for ^99mTc-HMPAO and ten for ^99mTc-ECD). Although both BPI^S and BPI^G values correlated significantly with the CBF^IMP values, the correlation coefficient in BPI^S was always better than that in BPI^G (r=0.869 for ^99mTc-HMPAO and r=0.929 for ^99mTc-ECD in BPI^S, r=0.629 for ^99mTc-HMPAO and r=0.856 for ^99mTc-ECD in BPI^G). These results suggest that SA can provide a more reliable BPI for quantifying CBF using ^99mTc-HMPAO or ^99mTc-ECD than the conventional method using GA. Our method will be useful especially when using a tracer with a low first-pass extraction fraction and/or when performing activation studies using pharmacological intervention. Received 3 November 1998 and in revised form 27 May 1999     

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.     

Technetium-99m human polyclonal immunoglobulin G studies and conventional bone scans to detect active joint inflammation in chronic rheumatoid arthritis

Rheumatoid arthritis is a chronic polyarthritis in which active inflammed joints coexist with joints in remission. We performed bone scans (^99mTc-DPD) and ^99mTc human polyclonal immunoglobulin G scans (^99mTc-IgG) in 18 patients with rheumatoid arthritis to assess the uptake in actively inflamed joints and in joints in which remission after inflammation had occurred. A quantitative analysis of tracer uptake in each joint was performed on both scans. In 123 joints without current active inflammation, an increased ^99mTc-DPD uptake was observed (2.31 ± 1.27), whereas no ^99mTc-IgG uptake was noted (1.18±0.32). Some 78 joints with mild pain or swelling exhibited increased ^99mTc-DPD uptake (2.48 ± 1.14) and increased ^99mTc-IgG uptake (1.76 ± 0.50; P <0.001), while 21 joints with moderate to severe pain or swelling exhibited increased ^99mTc-DPD uptake (2.39±0.93) and increased ^99mTc-IgG uptake (1.79±0.51; P <0.001). In conclusion, ^99mTc-IgG scans distinguish between joints with and without active inflammation in chronic rheumatoid arthritis, whereas bone scans do not. Thus, ^99mTc-IgG scans may be useful in identifying joints with current active inflammation in rheumatoid arthritis.Work was supported by a research grant from Mallinckrodt Ibér-ica Offprint requests to: L. Berná     

Tumour-like thallium-201 accumulation in brain infarcts,an unexpected finding on single-photon emission tomography

Thallium-201 brain single-photon emission tomography (²⁰¹Tl-SPET) is widely used to detect viable tumour tissue with increased metabolic activity. When reperfusion takes place early in cerebrovascular lesions of embolic origin, the presence of tissue areas with increased regional blood flow and preserved metabolic activity can also be assumed. In the present study our purpose was to investigate whether or not foci of ²⁰¹Tl accumulation occur in reperfused areas with sustained morphological integrity indicated by computed tomography (CT) scans not showing hypodensity in the acute or subacute period.In 16 stroke patients with possible cortical embolic infarction, dual ²⁰¹Tl and technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) SPET was performed in both the acute and the subacute period. ^99mTc-HMPAO SPET was performed to detect reperfusion. Follow-up CT scans from the same period were also available. In five cases ^99mTc-HMPAO SPET ruled out reperfusion and ²⁰¹Tl SPET was also negative. In four cases ^99mTc-HMPAO studies indicated reperfusion early in the acute phase (24–72 h), and comparative CT, without showing hypodensity in the acute or subacute period, also favoured the possibility of sustained metabolic activity. In these cases ²⁰¹Tl SPET was negative in both the acute and the subacute period. In seven cases CT already showed necrosis in ^99mTc-HMPAO hypoperfused areas in the acute period, with negative results on corresponding ²⁰¹Tl SPET. Later reperfusion occurred in the subacute period (8–14 days) as indicated by ^99mTc-HMPAO SPET, at which time an unexpected focal accumulation of ²⁰¹Tl was detected. We cannot give any explanation for the findings, but further studies might clarify the matter and improve our knowledge of the precise mechanism of ²⁰¹Tl uptake under different conditions. Until then the phenomenon should be borne in mind as a possible pitfall when assessing tissue viability.