99Tcm and 111In leucocyte scintigraphy in inflammatory bowel disease.

A comparative study of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and 111In leucocyte scintigraphy was performed in inflammatory bowel disease. Two hundred and thirty-four patients were studied, 146 had 99Tcm-HMPAO, 82 had 111In and six had both. The sensitivity, specificity and accuracy of the 99Tcm leucocyte scan were 96, 97 and 97%, respectively, and 96, 97 and 97%, respectively, for the 111In leucocyte scan. 99Tcm-HMPAO leucocytes demonstrated similar diagnostic accuracy to 111In-labelled leucocytes with improved image quality and reduced radiation dose.     

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.     

Technetium-99m nanocolloid for the scintigraphic assessment of inflammatory bowel disease in the colon: its value in comparison with indium-111-labelled granulocytes

The usefulness of 99mTc-nanocolloid for the assessment of localization and disease activity of colitis in patients suffering from inflammatory bowel disease (IBD) was investigated in 10 patients. Results of 99mTc-nanocolloid scintigraphy were compared with Indium-111 autologous granulocyte scintigraphy and the activity index according to Van Hees. In none of the patients a true positive result of the 99mTc-nanocolloid scintigraphy was encountered, while 111In-granulocyte scintigraphy was positive in 7 of 10 patients with active disease. Radioactivity became visible in the small bowel starting 2 h after injection of 99mTc-nanocolloid most likely because of excretion by the liver of degradation products of the radiopharmaceutical. The authors conclude that despite a previous communication 99mTc-nanocolloid cannot replace 111In-granulocytes for the assessment of IBD patients with active colitis.     

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     

Image quality and radiopharmaceutical parameters of indium-111 granulocytes in scintigraphy of inflammatory bowel disease

This study was undertaken to investigate the influence of various parameters of injected autologous 111In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of 111In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq 111In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.     

Image quality and radiopharmaceutical parameters of Indium-111 granulocytes in scintigraphy of inflammatory bowel disease

This study was undertaken to investigate the influence of various parameters of injected autologous ¹¹¹In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of ¹¹¹In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq ¹¹¹In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.Department of Gastroenterology     

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     

Radiation dosimetry of a 99mTc-labeled IgM murine antibody to CD15 antigens on human granulocytes.

99mTc-labeled anti-stage specific embryonic antigen-1 (anti-SSEA-1) is an injectable IgM antibody derived from mice. It binds to CD15 antigens on some granulocytic subpopulations of human white blood cells in vivo after systemic administration. The purpose of this study was to measure biodistribution of 99mTc-labeled anti-SSEA-1 and perform radiation dosimetry in 10 healthy human volunteers. METHODS: Transmission scans and whole-body images were acquired sequentially on a dual-head camera for 32 h after the intravenous administration of about 370 MBq (10.0 mCi) of the radiopharmaceutical. Renal excretion fractions were measured from 10 to 14 discrete urine specimens voided over 27.9 +/- 2.0 h. Multiexponential functions were fit iteratively to the time-activity curves for 17 regions of interest using a nonlinear least squares regression algorithm. The curves were integrated numerically to yield source organ residence times. Gender-specific radiation doses were then estimated individually for each subject, using the MIRD technique, before any results were averaged. RESULTS: Quantification showed that the kidneys excreted 39.5% +/- 6.5% of the administered dose during the first 24 h after administration. Image analysis showed that 10%-14% of the radioactivity went to the spleen, while more than 40% went to the liver. Residence times were longest in the liver (3.37 h), followed by the bone marrow (1.09 h), kidneys (0.84 h) and the spleen (0.65 h). The dose-limiting organ in both men and women was the spleen, which received an average of 0.062 mGy/MBq (0.23 rad/mCi, range 0.08-0.30 rad/mCi), followed by the kidneys (0.051 mGy/MBq), liver (0.048 mGy/MBq) and urinary bladder (0.032 mGy/MBq). The effective dose equivalent was 0.018 mSv/MBq (0.068 rem/mCi). CONCLUSION: The findings suggest that the radiation dosimetry profile for this new infection imaging agent is highly favorable.     

Comparison of technetium 99m polyclonal human immunoglobulin and technetium 99m monoclonal antibodies for imaging chronic osteomyelitis

The accuracy of technetium-99m human immunoglobulin (HIG) for the detection of chronic osteomyelitis (OM) was compared with white blood cell scintigraphy using^99mTc-labelled monoclonal mouse antibodies (MAB). Seventeen patients suspected of having OM in 20 lesions went through three-phase skeletal scintigraphy, HIG scintigraphy and MAB scintigraphy. The final diagnosis was established by open surgery, histology and bacteriology. Chronic OM was proved in 14/20 lesions. Six of these 14 infections were located in peripheral areas without active bone marrow and 8/14 in central areas with active bone marrow. In peripheral OM, 5/6 with HIG and 6/6 with MAB were true positives. In the central skeleton all 8/8 infections appeared as cold lesions in the MAB study, which were defined as being false negative due to their non-specificity. Using HIG, 5/8 central infections were determined to be truly positive by showing photon-rich lesions. These 5 lesions were located in the hip region and in the pelvis, whereas 3 lesions of the spine were missed. There were no false-positive results in either studies. In conclusion, MAB was superior to HIG in peripheral OM concerning sensitivity, anatomical landmarks and differentiation of soft tissue versus bone infection. In central OM MAB detected all lesions accurately, but no differential diagnosis was possible due to the non-specificity of photon-low areas. In this respect HIG seems to be more specific due to the increased accumulation even in central infection sites.     

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.     

Mechanism of localization of 99mTc-labeled pyrophosphate and tetracycline in infarcted myocardium.

The gross and subcellular localizations of 99mTc-labeled pyrophosphate and tetracycline in myocardial infarcts were studied in a rabbit model. Experiments utilizing double-nuclide labeling were carried out using a useful mapping technique. Concentration of the various chelates decreases in an expected manner from the center of the infarcted area toward its periphery, but it is higher near the epicardial surface than toward the endocardium. Technetium-99m-pyrophosphate is concentrated in the same infarcted areas as 45Ca ion or 32P-pyrophosphate, but to a much greater degree. The uptake is dependent on both the degree of necrosis and residual blood flow. Gel filtration experiments with rabbit serum indicate that 99mTc-tagged pyrophosphate, tetracycline, and diphosphonate are mainly protein-bound, whereas 32P-pyrophosphate is not. Subcellular localization studies show that 99mTc-tetracycline and 99mTc-pyrophosphate are bound primarily to soluble protein, and only a small fraction is associated with nuclei, mitochondria, and microsomes. The uptake of technetium chelates in myocardial infarcts may be due to the formation of polynuclear complexes with denatured macromolecules rather than to the deposition of calcium in mitochrondria.     

99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans.

In recent years, imaging tumors with receptor-specific biomolecules has been the focus of increasing interest. Vasoactive intestinal peptide (VIP) has a high affinity for specific receptors that are expressed in high density on a large number of malignant tumors. VIP was modified (TP 3654) without compromising its biologic activity and labeled with 99mTc. Pharmacokinetics and feasibility studies were performed in 3 healthy volunteers and 11 patients with a history of cancer. Imaging was performed for up to 2 h after injection. Within 24 h after injection of 99mTc-TP 3654 (370-555 MBq/5 microg), approximately 70% of the tracer cleared through the kidneys and 20% through the liver. Blood clearance was rapid. No adverse reaction was noted in any subject. All known tumors were clearly delineated within 20 min. Findings were compared with the results of 99mTc-methoxyisobutyl isonitrile, CT, MRI, or histology. There was concordance in 9 patients. In the other 2 patients, only the VIP scan was positive for tumors known to express VIP receptors. The early results of imaging tumors with 99mTc-VIP are promising and warrant further study.     

Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations

Recently a new linker — hydrazinonicotinate (HYNIC) — was introduced for labelling of proteins and peptides with technetium-99m. HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with^99mTc for the detection of infections. In this study we compared the tissue distribution of three different^99mTc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection withStaphylococcus aureus. We compared^99mTc-HYNIC-hIgG with^99mTc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the^99mTc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of^99mTc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of^99mTc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%±0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%±0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of^99mTc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of^99mTc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that^99mTc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.     

Radiolabelled granulocytes in inflammatory bowel disease: diagnostic possibilities and clinical indications

Radiolabelled granulocytes in chronic inflammatory bowel diseases (CIBD) are able to diagnose the disease extent and assess the disease activity. It may be performed with 111In oxine- and 99Tcm hexamethylpropyleneamineoxime (HMPAO)-labelled cells. The granulocyte scan localizes inflamed bowel segments with an accuracy comparable with radiology and endoscopy including biopsy of the bowel (r = 0.95; P less than 0.001). The specificity of the scan for diseased segments is near 100%, the sensitivity 92%. A three-phase white blood cell scan (imaging: 0.5, 4, 20 h post injection) allows differentiation of diseased bowel segments from abscesses and fistulas. False positive results are possible in necrotic carcinomas. The 99Tcm HMPAO scan shows rapid renal and delayed biliary and intestinal excretion of tracer. In this way diagnostic problems arise in the small pelvis. Because of the intestinal and biliary excretion, early images should be obtained (0.5-2 h post injection). Later scans with 99Tcm HMPAO are of minor importance. The disease activity can very specifically be assessed by the determination of the percentage faecal 111In excretion (96 h faecal collection). Active and non-active diseases can be clearly differentiated. We found no correlation with the subjectively influenced Crohn's disease activity index (CDAI) (r = 0.25; P greater than 0.05), but good correlations with the Dutch Index (van Hees: r = 0.67), ESR (r = 0.69), serum albumin (r = -0.54) and orosomucoid (r = 0.65). The percentage faecal excretion correlates well with the histologically estimated leucocytic bowel infiltration. Because of the intestinal 99Tcm HMPAO excretion the determination of faecal excretion is pointless in 99Tcm studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Scintigraphic head-to-head comparison between 99mTc-WBCs and 99mTc-LeukoScan in the evaluation of inflammatory bowel disease: a pilot study

Scintigraphy with technetium-99m labelled white blood cells (WBCs) is routinely used in our hospital for the assessment of inflammatory bowel disease (IBD). The main disadvantages of this diagnostic tool are its time-consuming nature and the handling of blood itself. 99mTc-LeukoScan is a relatively new, easily prepared agent that is used for the detection of osteomyelitis. To assess its value in IBD, a scintigraphic head-to-head comparison was performed between 99mTc-LeukoScan and 99mTc-WBCs. 99mTc-LeukoScan scintigraphy was performed in six patients with clinically active IBD and increased uptake on 99mTc-WBC images. The interval between the scintigraphic studies ranged from 2 to 7 days, and endoscopy was subsequently performed to confirm active IBD. In three out of six patients with increased uptake on the 99mTc-WBC scans, 99mTc-LeukoScan images showed very discreet activity in the bowel, but the sites did not correspond with the inflammation sites seen on 99mTc-WBC scintigraphy and found at endoscopy. In the other three patients, 99mTc-LeukoScan scintigraphy revealed a physiological distribution but no abnormalities. In conclusion, 99mTc-LeukoScan is not an alternative agent for the assessment of IBD. A prospective study is not justified owing to the false-negative results.