Technetium-99m scintigraphy: more accurate assessment of ulcerative colitis with exametazime-labelled leucocytes than with antigranulocyte antibodies

To compare two technetium-99m scintigraphic techniques —^99mTc-labelled antibodies against granulocyte non-specific cross-reacting antigen-95 and^99mTc-exametazime labelled leucocytes in ulcerative colitis —23 consecutive patients undergoing colonoscopy were investigated in a prospective and randomized study. In each patient the two scans and colonoscopy and biopsy were performed within 10 days. Scans, endoscopy and histology were independently graded for degree of inflammation in eight different colorectal segments for each patient. Active inflammation in one or more segments was present on endoscopy in 22 patients and on histology in 17 patients. Twenty-two patients had increased uptake on the antibody scan and 21 patients on the exametazime scan. Twelve patients showed the same disease extent with both scan methods (total colitis,n=10; distal colitis,n=2). Compared with endoscopy, sensitivity for inflammation in individual segments was 0.51 for antibody scan and 0.87 for exametazime scan; specificity was 0.67 and 0.55, respectively. The predictive value for presence of inflammation was 0.66 for antibody scan and 0.72 for exametazime; the predictive value for absence of inflammation was 0.52 and 0.77, respectively. Segmental scan uptake of endoscopically or histologically visualized inflammation was consistently lower for antigranulocyte antibodies than for exametazime. It is concluded that in patients with active ulcerative colitis, inflammation is better visualized with^99mTc-exametazime labelled leucocytes than with^99mTc-labelled antigranulocyte antibodies. The antibody technique offers the advantage of in vivo labelling, but is less reliable than the exametazime method for imaging of colonic inflammation.     

Upregulation of granulocyte CD11b (CR 3) after labelling with technetium-99m hexamethylpropylene amine oxime

Today technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) is widely used for leucocyte scintigraphy, as^99mTc-HMPAO selectively labels granulocytes in mixed leucocyte suspensions. However, the influence of cell labelling on the expression of specific adhesion proteins has not been studied before. Therefore, we investigated five patients, four of whom had established Crohn's disease. We found that leucocyte labelling with^99mTc-HMPAO induces increased expression of the glucoprotein receptor CD11b on granulocytes, but it is not clear whether this upregulation affects the functional integrity of the granulocytes.     

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.     

Radiochemistry and biostability of autologous leucocytes labelled with 99mTc-stannous colloid in whole blood

Autologous leucocytes were labelled in whole blood by phagocytic uptake of ^99mTc-stannous colloid. This colloid has a mean particle size of 1.5 m and labels leucocytes with 81% efficiency. Individual cell uptakes were: granulocytes 42%, monocytes 39%. Isotonic sodium citrate added after the labelling procedure did solubilise excess colloid but was not necessary for adequate removal of excess colloid. Labelled leucocytes were shown in vitro to be viable and maintain normal bactericidal and chemotactic capacity. Biodistribution, clearance rates and dosimetry are presented. These results indicate that autologous leucocytes can be efficiently labelled with ^99mTc-stannous colloid with good residual cell function.     

Cell labelling with colloidal substances in whole blood

A method for the labelling of leucocytes with ^99mTc-colloid is described. The labelling can be done in samples of whole blood, because the colloid is only taken up by the phagocytosing cells, the monocytes and the granulocytes. The part of the colloid that is not phagocytosed is brought to a soluble state with Na-citrate, so that only the phagocytosed colloid is reinjected. The labelling efficiency with this method is between 80% and 90%. Measurements of the activity in the leucocytes 3 h after reinjection, have shown that at least 50% of the labelled cells are at this time still available in the blood pool.The clinical results on 32 patients with the tentative diagnosis of an abdominal abscess and on 42 patients with the tentative diagnosis of septic loosening of an endoprosthesis have shown that the labelled leucocytes are very well suited to show up local foci of inflammation.     

Synthesis of 99mTc-HYNIC-interleukin-12, a new specific radiopharmaceutical for imaging T lymphocytes

Purpose Few radiopharmaceuticals have been described for the study of lymphocyte trafficking despite its high clinical relevance. The main difficulty resides in the identification of a suitable highly specific probe to target these cells. Interleukin-12 (IL12) is a heterodimeric cytokine which plays a key role in the development of Th₁ lymphocytes. The aims of the present study were to label IL12 with ^99mTc, to evaluate its ability to bind to activated T lymphocytes in vitro and to study its biodistribution in normal mice and mice affected by autoimmune colitis. Methods IL12 was derivatised with HYNIC-NHS and labelled with ^99mTc. An in vitro binding assay was performed on KIT225 cells, an IL12 receptor-positive cell line. ^99mTc-IL12 biodistribution in normal mice was studied. Targeting experiments were performed in Balb/c mice injected with KIT225 cells and in mice with chemically induced chronic colitis. Results ^99mTc-IL12 labelling efficiency ranged between 75% and 85%. Saturation binding analysis revealed a K _d of 2.09 nM. Results of biodistribution studies showed a predominant hepatic route of excretion. A significant degree of uptake in the spleen and thymus was also observed. In mice injected with KIT225 cells, ^99mTc-IL12-specific uptake in these cells increased over time. ^99mTc-IL12 also accumulated significantly in bowel of mice affected by TNBS-induced colitis showing T lymphocyte infiltration at histology, while accumulation in colon from control animals was negligible. Conclusion We conclude that this radiolabelled cytokine is a suitable candidate for specific in vivo imaging of T lymphocytes: a step forward in molecular imaging of immune-mediated processes.     

99mTc-interleukin-2 and 99mTc-HMPAO granulocyte scintigraphy in patients with inactive Crohn's disease

Crohn's disease (CD) is a chronic inflammatory bowel disease that may involve the whole gut. Marked intestinal T cell and macrophage activation is a key feature of the disease. Polymorphonuclear cell infiltration is also observed in the diseased gut, mainly during active inflammation. Scintigraphic detection of granulocytes and activated lymphocytes infiltrating the gut wall may be useful in identifying a subgroup of patients with clinically inactive CD who are undergoing early clinical relapse. The aims of the present study were (a) to compare the effectiveness of scintigraphy with (99m)Tc-labelled interleukin-2 ((99m)Tc-IL2) and with (99m)Tc-HMPAO labelled granulocytes ((99m)Tc-WBC) in detecting the presence and extent of bowel inflammation in patients with long-term inactive CD (>12 months) and (b) to assess the accuracy of these techniques in predicting future disease relapse. We studied 29 patients with ileal and/or colonic CD in stable clinical remission (Crohn's Disease Activity Index <150 for at least 12 months) using both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy in order to evaluate the extent of acute and chronic inflammation in the bowel. Planar and single-photon emission tomography images were acquired in each patient at 1 h p.i. For quantitative analysis of (99m)Tc-IL2 uptake, the abdomen was divided into 32 regions of interest. Despite the absence of symptoms, 18 patients (62%) showed a positive (99m)Tc-IL2 and 18 (62%) a positive (99m)Tc-WBC scan. Only 12 patients (41.4% of the total group) were positive on both scans, and the sites of IL2 and granulocyte bowel uptake were usually located in different segments, indicating that in CD, acute and chronic inflammation can be present in different sites. As far as the prognostic role of the two scans in predicting future disease relapse is concerned, both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy showed a high negative predictive value (1.00 and 0.91, respectively) but a weak positive predictive value (0.44 and 0.39, respectively). Nevertheless, Kaplan-Meier curves generated between scintigraphic findings and time free from disease relapse were statistically different only for (99m)Tc-IL2 scintigraphy (log-rank test, P=0.013). These results indicate that (99m)Tc-IL2 scintigraphy can be useful in selecting CD patients in clinical remission who could benefit from preventive therapy to avoid disease relapse.     

Radiochemistry and biostability of autologous leucocytes labelled with 99mTc-stannous colloid in whole blood

Autologous leucocytes were labelled in whole blood by phagocytic uptake of 99mTc-stannous colloid. This colloid has a mean particle size of 1.5 micron and labels leucocytes with 81% efficiency. Individual cell uptakes were: granulocytes 42%, monocytes 39%. Isotonic sodium citrate added after the labelling procedure did solubilise excess colloid but was not necessary for adequate removal of excess colloid. Labelled leucocytes were shown in vitro to be viable and maintain normal bactericidal and chemotactic capacity. Biodistribution, clearance rates and dosimetry are presented. These results indicate that autologous leucocytes can be efficiently labelled with 99mTc-stannous colloid with good residual cell function.     

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     

Use of perchlorate to block gastric uptake of free 99Tcm in the investigation of gastrointestinal bleeding

The use of perchlorate to block gastric uptake of free 99Tcm-pertechnetate after in vivo labelling of red cells was investigated. In 19 out of 20 cases there was no evidence that previous administration of perchlorate adversely affected red cell labelling using commercial stannous agents. Adequate scintigraphic images of the vascular system could be obtained for up to 24 h after the cells were labelled. The technique was found to be of value in the investigation of sites of gastrointestinal bleeding.     

Evaluation of technetium-99m exametazime stabilised with cobalt chloride as a blood flow tracer in focal cerebral ischaemia

A protocol has been devised to effectively extend the limited post-reconstitution shelf life of technetium-99m exametazime as a radiopharmaceutical for imaging cerebral blood flow (CBF) distribution. The potential of ^99mTc-exametazime stabilised with cobalt chloride for imaging CBF distribution as late as 4 h after reconstitution has been examined in ischaemic and nonischaemic tissue in halothane-anaesthetised cats. Focal cerebral ischaemia was produced by permanent middle cerebral artery occlusion. The relationship between ^99mTc-exametazime uptake and retention and CBF (assessed with [¹⁴C]iodoantipyrine 10 min after first radiopharmaceutical administration) was determined in the same tissue section with double label autoradiography. Over the CBF range 0 – 80 ml 100 g^–1 min^–1, the uptake of ^99mTc-exametazime (quantitatively and topographically) was linearly related to CBF irrespective of whether the ^99mTc-labelled tracer was unstabilised (and administered within 10 min of reconstitution) or was stabilised with cobalt chloride (and administered up to 240 min after reconstitution). For levels of CBF in excess of 80 ml 100 g^–1 min^–1 the excellent topographical relationship between ^99mTc-exametazime distribution and CBF is maintained but quantitatively, ^99mTc-exametazime underestimates CBF to a similar degree in animals receiving stabilised and unstabilised ^99mTc-exametazime. The presence of the stabiliser, cobalt chloride, extends greatly the period over which ^99mTc-exametazime can be used after reconstitution to generate images of CBF distribution in normal and ischaemic cerebral tissue.     

Scintigraphic findings on99mTc-MDP,99mTc-sestamibi and99mTc-HMPAO images in Gaucher's disease

Gaucher's disease is an autosomal recessive lysosomal storage disease characterized by the specific deficiency of glucocerebrosidase that leads to accumulation of insoluble glucocerebroside in the reticuloendothelial system, particularly the bone marrow, liver, spleen and lymph nodes. Direct scintigraphic visualization of lipid deposits in Gaucher's disease has recently been described, based on the use of the lipid-soluble xenon-133. We report here on the use of the lipophilic cat-ionic complex technetium-99m sestamibi (^99mTc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow;^99mTc-hexametazime (^99mTc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher's disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with^99mTc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of^99mTc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent^99mTc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27–1.48). The results obtained in this patient suggest a potential role of^99mTc-MIBI in the scintigraphic evaluation of Gaucher's lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over¹³³Xe because of its wider availability and greater practicality (i.v. administration of^99mTc-MIBI versus inhalation of¹³³Xe, and use of a single gamma camera instead of two as with¹³³Xe).     

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.     

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.     

Macrophage targeting with technetium-99m labelled J001 acylated poly-galactoside for scintigraphy of inflammation: Optimization and assessment of imaging specificity in experimental arthritis

J001, an acylated poly-(1,3)-galactoside purified from the membrane ofKlebsiella pneumoniae, associates selectively with macrophages via the binding to CD11b and CD14 molecules. Inflammatory foci known to recruit macrophages could thus be imaged with technetium-99m labelled J001. This study aims to define the optimal scintigraphic protocol for^99mTc-J001 imaging and to evaluate the specificity of J001 scans. A dose range study was conducted in rabbits with immunological arthritis using six different specific activities ranging from 370 to 11840 MBq·mg^–1 while the intravenously injected activity was constant (37 MBq) Radiochemical purity for each preparation was documented together with the in vivo stability of the^99mTc-J001 complex using exclusion-diffusion radioHPLC of serum collected 1 h after radiopharmaceutical administration. Scintigraphic images were recorded at 2, 3 and 4 h and analysed using indexes calculated from regions of interest. Specificity of the macrophage imaging was assessed by comparison with scans obtained after administration of^99mTcO₄ ^– or^99mTc-albumin nanocolloids. A protocol of plasma transfusion was also used to inject^99mTc-J001 after complete removal of radioactive colloids likely to be generated during the labelling. For the higher specific activities (5920 and 11840 MBq·mg^–1), radiochemical purity degradation and in vitro^99mTc transchelation were noted. To prevent transchelation and^99mTc bond hydrolysis likely to impair imaging specificity, 1480 MBq·mg^–1 corresponding to 25 µg injected J001 was found to be the optimal usable specific activity. Results obtained with the various tracers support the hypothesis that macrophage targeting is the main factor involved in the J001 imaging of arthritis.     

In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of 99mtechnetium stannous colloid but do not affect neutrophil uptake

INTRODUCTION: (99m)Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. METHODS: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. RESULTS: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. CONCLUSIONS: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects of these cytokines on CD11b/CD18 expression.     

In vivo and in vitro multitracer analyses of P-glycoprotein expression-related multidrug resistance

P-glycoprotein (Pgp) is an ABC (ATP binding cassette) transporter that is often overexpressed in tumours, contributing significantly to their multidrug resistance. In this study, we explored whether the radiotracers used in tumour diagnostics can be used for in vivo visualisation of Pgp-related multidrug resistance. We also examined the effects of different Pgp modulators on the accumulation of these radioligands in tumours with or without Pgp expression. In a SCID BC-17 mouse model, cells of the drug-sensitive KB-3-1 (MDR^–) and the KB-V1 Pgp-expressing (MDR⁺) human epidermoid carcinoma cell lines were inoculated to yield tumours in opposite flanks. For in vivo scintigraphic (biodistribution) and positron emission tomography (PET) examinations, the mice were injected with technetium-99m hexakis-2-methoxybutylisonitrile (^99mTc-MIBI), carbon-11 labelled methionine and fluorine-18 fluoro-2-deoxy-d-glucose (¹⁸FDG). For validation, in vitro cell studies with ^99mTc-MIBI, ^99mTc-tetrofosmin, [¹¹C]methionine and ¹⁸FDG were carried out using a gamma counter. The expression and function of the MDR product were proved by immunohistochemistry and spectrofluorimetry. ^99mTc-MIBI uptake was significantly lower in KB-V1 cells as compared with KB-3-1-derived tumours in vivo (Pgp⁺/Pgp^– =0.61±0.13; P<0.01) and cells in vitro (Pgp⁺/Pgp^– =0.08±0.01; P<0.001). Cyclosporin A reversed ^99mTc-MIBI uptake in the Pgp+ cells, while verapamil failed to modify it. ¹⁸FDG uptake was significantly higher in KB-V1 tumours (Pgp⁺/Pgp^– =1.36±0.05; P<0.01) and cells (Pgp⁺/Pgp^– =1.52±0.12; P<0.001). Whereas cyclosporin A eliminated the difference between FDG uptake in MDR⁺ and MDR^– cell lines, verapamil significantly increased it. When the animals were treated with verapamil, the ratio of ^99mTc-MIBI uptake in the MDR⁺ tumours to that in the MDR^– tumours decreased to 0.38±0.05 (P<0.01), while the ratio of ¹⁸FDG uptake increased to 2.1±0.3 (P<0.001). There were no significant differences in the [¹¹C]methionine uptake in the MDR⁺ and MDR^– tumours and cell lines, nor was [¹¹C]methionine accumulation modified by cyclosporin A. Parallel administration of ¹⁸FDG and ^99mTc-MIBI combined with verapamil treatment seems to be a good candidate as a non-invasive marker for the diagnosis of MDR-related Pgp expression in tumours.     

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     

Intestinal accumulation of 111In-granulocytes in patients studied because of occult infection

¹¹¹In-granulocyte scintigraphy was performed on 245 patients in whom a localized infection was suspected. In 123 patients scintigraphy was positive and of these 35 (28%) had intestinal accumulations of ¹¹¹In-granulocytes. Specific local causes for the intestinal uptake of radioactivity were antibiotic associated colitis (eight patients), local pyogenic bowel infection (four patients), systemic disease (two patients), bowel necrosis (two patients), colonic cancer (one patient) and Stevens-Johnson's syndrome (one patient). Nonspecific mechanisms of bowel accumulation were desquamation of labelled granulocytes (12 patients) and bleeding (two patients). In three cases the mechanism of colonic accumulation of granulocytes was not revealed. These results show that unexpected accumulations of labelled granulocytes in the gut is not a rare phenomenon and is often due to clinically significant intestinal inflammation or other disease, especially in patients who do not have signs of respiratory, pancreatic or oesophageal inflammation causing desquamated granulocytes to accumulate in the gut.     

First evaluation of technetium-99m dimercaptopropionyl albumin as a possible tracer agent for ventriculography in a volunteer

Technetium-99m labelled red blood cells (^99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). ^99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3di(S-acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3-dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with ^99mTc at room temperature by simple addition of stannous ions and eluate of a ^99mTc generator. After evaluation in mice and rabbits, two different ^99mTc-DMP-HSA preparations — obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 — were tested in a volunteer and compared to ^99mTcRBCs. The blood time-activity curves of the three preparations were quite similar but both ^99mTc-DMP-HSA preparations were excreted much less into the urine than ^99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both ^99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle. However, a slightly higher liver uptake was seen with ^99mTc-DMP-HSA 16:1, whereas the liver uptake of ^99mTc-DMP-HSA 8:1 and ^99mTc-RBCs was the same. These first results suggest that ^99mTc-DMP-HSA, and in particular ^99mTc-DMP-HSA 8:1, could be used for ventriculography as a practical and reliable alternative to ^99mTc-RBCs.