13th Meeting of the International Research Group on Immunoscintigraphy and Immunotherapy (IRIST). 7-8 May 1999, Göttingen, Germany.
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Humans↗
Biomedical subjects
O C Boerman
Publications and source records attributed to O C Boerman.
Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.
Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.
Adult↗
Scintigraphic imaging of bacterial and fungal infection in granulocytopenic rats.
UNLABELLED: Scintigraphic imaging in granulocytopenic patients can be very useful to detect and localize infections, which often do not show localizing signs and symptoms. We studied the potential of 99mTc-labeled polyethylene glycol (PEG)-coated liposomes and 99mTc-labeled IgG to image bacterial and fungal infection in a granulocytopenic rat model. 67Ga-citrate was used as a reference agent. METHODS: 99mTc-PEG-liposomes, 99mTc-hydrazinonicotinate (HYNIC)-IgG or 67Ga-citrate was administered to granulocytopenic rats with a Staphylococcus aureus abscess or with unilateral invasive pulmonary aspergillosis. Imaging and biodistribution studies were performed. RESULTS: All agents visualized the S. aureus infection from 1 h after injection onward. However, only with 99mTc-PEG-liposomes and with 99mTc-HYNIC-IgG did activity in the infectious foci increase with time up to 24 h. 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG showed significantly higher accumulation in the infectious focus compared with 67Ga-citrate (1.33+/-0.31 and 1.40+/-0.16 percentage injected dose per gram [%ID/g], respectively, versus 0.31+/-0.04 %ID/g 24 h after injection; P<0.05). At 24 h after injection, abscess-to-muscle ratios were highest for 99mTc-liposomes (72.1+/-19.1), followed by 99mTc-HYNIC-IgG (18.3+/-3.3) and 67Ga-citrate (4.4+/-0.7). In pulmonary aspergillosis, both 99mTc-PEG-liposomes and 99mTC-HYNIC-IgG showed significantly higher uptake in the infected lung than did 67Ga-citrate (3.6+/-0.4 and 8.3+/-0.8 %ID/g, respectively, versus 1.3 %ID/g at 24 h after injection; P<0.05). CONCLUSION: 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG performed better than did 67Ga-citrate in the localization of peripheral bacterial infection and fungal infection in the lung in granulocytopenic rats. The high focal uptake and high target-to-nontarget ratios of 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG indicate that both radiopharmaceuticals may become valuable agents to image infection in granulocytopenic patients.
Abscess↗
A novel method to label liposomes with 99mTc by the hydrazino nicotinyl derivative.
UNLABELLED: In this study a new 99mTc labeling method for polyethyleneglycol (PEG)-coated liposomes is described. The in vitro and in vivo characteristics were compared with the conventional 99mTc-HMPAO-labeled PEG-coated liposomes. METHODS: PEG-coated liposomes were labeled with 99mTc by the hydrazino nicotinyl (HYNIC) derivative of distearoylphosphatidyl-ethanolamine (DSPE) and compared with PEG-coated liposomes labeled with 99mTc-HMPAO. In vitro stability tests were performed. Biodistribution and imaging characteristics of both liposomal preparations were determined in rats with Staphylococcus aureus infection in the left calf muscle. RESULTS: Per liposome, 230 hydrazine groups were incorporated. The labeling efficiency of the 99mTc-HYNIC liposomes was greater than 95%, so no postlabeling purification was required, in contrast to the 99mTc-HMPAO liposomes. The 99mTc-HYNIC liposomes showed greater in vitro stability than the conventional 99mTc-HMPAO liposomes. Abscess uptake of the 99mTc-HYNIC liposomes was significantly greater (1.74+/-0.38%ID/g versus 1.26+/-0.29%ID/g, 24 h postinjection, P < 0.03). Furthermore, kidney uptake of the 99mTc-HYNIC liposomes was one third of the uptake of the 99mTc-HMPAO liposomes (0.79+/-0.07%ID/g versus 2.47+/-0.35%ID/g, 24 h postinjection, P < 0.0001). CONCLUSION: This new 99mTc-HYNIC-based labeling method for liposomes is rapid, efficient and easy to perform. Most importantly, the 99mTc-labeled liposomes have an improved stability and in vivo characteristics. The new labeling method is a major step forward toward a radiopharmaceutical for infection imaging that can be prepared in a one-step procedure within 15 min at room temperature and thus can be applied in every routine clinical practice.
Abscess↗
Two-step radio-immunotargeting of renal-cell carcinoma xenografts in nude mice with anti-renal-cell-carcinoma X anti-DTPA bispecific monoclonal antibodies.
The specificity of antibodies offers unique opportunities to target tumors with radionuclides. However, due to the slow clearance of radiolabeled antibody, relatively high back-ground is observed in non-target organs. Pre-targeting protocols using bispecific monoclonal antibodies (bsMAbs) and radiolabeled chelates may overcome this problem. We have evaluated the anti-renal-cell-carcinoma (RCC) X anti-DTPA bsMAb G250 x DTIn1 for 2-step targeting of RCC tumors in nude mice. Tumor uptake of 111In-DTPA was similar up to a 3-day interval between bsMAb and 111In-DTPA injections and decreased thereafter. The effect of G250 x DTIn1 protein dose was studied. High tumor uptake was seen at 1 to 4 micrograms, whereas at higher doses uptake decreased. Tumor was saturated with 15 micrograms bsMAb. At the saturating bsMAb dose the 111In-DTPA amount was varied. High tumor uptake was observed at a 10-fold molar excess 111In-DTPA, whereas at higher excess uptake decreased. After priming with 15 micrograms bsMAb and targeting with a 10-fold molar excess 111In-DTPA, the biodistribution of 111In-DTPA was studied for 1 to 48 hr after injection. Good tumor retention of 111In-DTPA was observed, while the radiolabel cleared rapidly from the blood. Consequently, tumor-to-blood ratios increased with time to 500 at 24 hr after injection. In conclusion, RCC xenografts can be targeted efficiently using G250 x DTIn1 and 111In-DTPA. However, this requires careful tuning of bsMAb protein dose and 111In-DTPA dose. Using the optimal protein dose and 111In-DTPA dose, high 111In-DTPA tumor uptake and tumor-to-blood ratios can be obtained, thus providing good perspectives for diagnostic and therapeutic use in humans.
Animals↗
Bacterial lipopolysaccharide binds and stimulates cytokine-producing cells before neutralization by endogenous lipoproteins can occur.
Lipoproteins are able to bind to lipopolysaccharide (LPS) and neutralize its deleterious effects. However, it is not clear why the LPS-binding capacity of circulating lipoproteins, which is 10- to 10 000-fold above the maximal LPS concentrations found in septic patients, is not sufficient to inhibit the effects of LPS during an infection, whereas infusion of exogenous lipoproteins has a potent inhibitory action. In this study, the kinetics of LPS-neutralization by VLDL, LDL, and HDL were investigated, at lipoprotein-to-LPS ratios found in severe Gram-negative sepsis. At least 4-8-h preincubation of LPS with either LDL or HDL were necessary to inhibit 50% of the LPS-induced TNF-alpha production by human peripheral blood mononuclear cells (PBMC), whereas after 24 h of preincubation LDL or HDL strongly inhibited the TNF-alpha synthesis (70-90%, P<0.01). VLDL was the least effective lipoprotein fraction. In contrast, FITC-LPS bound to PBMC much more rapidly, with 70% of the total binding after 30 min, and 90% after 1-h incubation. The increase of LDL or HDL concentrations up to 10-fold (as in experimental models of hyperlipoproteinaemia) was able not only to further decrease TNF-alpha production after long LPS-lipoproteins preincubation periods, but also to improve the kinetics of LPS neutralization. In conclusion, LPS binds and stimulates the mononuclear cells in circulation before neutralization by endogenous lipoproteins can occur. Additional increase in the lipoprotein-to-LPS molar ratio (e.g. by infusion of exogenous lipoproteins) accelerates the kinetics of LPS neutralization, and may be useful as adjunctive therapy in severe Gram-negative infections.
Dose-Response Relationship, Drug↗
Imaging of infection in rabbits with radioiodinated interleukin-1 (alpha and beta), its receptor antagonist and a chemotactic peptide: a comparative study.
Previous studies have reported the favourable characteristics of chemotactic peptides and interleukins for imaging of infection and inflammation. In the present study, the potential of two species of interleukin 1 (IL-1), IL-1alpha and IL-1beta, the IL-1 receptor antagonist (IL-1ra) and the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanyl-lysine (fMLFK) were directly compared in a rabbit model of infection. IL-1alpha, IL-1beta, IL-1ra and fMLFK were labelled with iodine-123 according to the Bolton-Hunter method. Twenty-four hours after induction of Escherichia coli abscesses in the left thigh muscle, rabbits were injected intravenously with 0.5 mCi of 123I-labelled agent. Gamma camera images were obtained at 5 min and 1, 4, 8 and 20 h p.i. Biodistribution was determined at 20 h p.i. Although all agents rapidly cleared from the blood, at 20 h p.i. blood levels and the levels in most organs of 123I-fMLFK were significantly lower than those of the other three agents (P<0.05). The abscesses were clearly visualized with all agents from 4 h p.i. onwards. After 1 h p.i., the abscess uptake of 123I-IL-1beta was significantly higher than that of the other agents (P<0.05), with the highest uptake observed at 8 h p.i. (1.3%+/-0.3%). After 20 h p.i., the highest abscess-to-contralateral muscle ratios were obtained with 123I-IL-1beta, i.e. 39.0+/-11.5 vs 18.7+/-5.4, 18.1+/-2.3 and 29. 9+/-7.0 for 123I-IL-1alpha, 123I-IL-1ra and 123I-fMLFK, respectively. In conclusion, all agents localized in the infectious focus. The potential of radiolabelled IL-1beta for imaging of infection was better than that of the other agents: higher absolute uptake in the infection and higher abscess-to-contralateral muscle ratios were obtained. The observation of localization of radiolabelled IL-1ra in infection was important since this protein can be administered to humans without any side-effects.
Abscess↗
Scintigraphic detection of infection and inflammation: new developments with special emphasis on receptor interaction.
Various conventional radiopharmaceuticals are currently available for scintigraphic imaging of infection and inflammation. Although a wide variety of infectious and inflammatory foci can be detected with these agents, several disadvantages limit their application. These limitations have stimulated the search for new radiopharmaceuticals. In the past decade a new class of radiopharmaceuticals has emerged: radiolabelled receptor-specific small proteins and peptides. These proteins and peptides are naturally occurring inflammatory mediators which specifically bind to receptors abundantly present in the area of inflammation. In addition, owing to their small size, they rapidly clear from all non-target tissues. This paper provides an overview of these newly developed agents, focussing on imaging characteristics and in vivo uptake mechanisms.
Animals↗
Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration.
In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.
Adolescent↗
Immunohistochemical analysis of intratumoral heterogeneity of [131I]cG250 antibody uptake in primary renal cell carcinomas.
In previous studies, highly heterogeneous uptake of 131I-labelled chimeric monoclonal antibody G250 ([131I]cG250) in primary renal cell carcinomas has been observed (intratumoral differences > factor 100). In this study, we investigated a possible correlation between intratumoral antibody uptake and four immunohistochemically determined parameters: G250 antigen expression, blood vessel density, neovascularization and percentage of viable tumour cells. Whole tumour slices of four different tumours were cut into 1-cm3 cubes, and in each cube the [131I]cG250 uptake was determined. The correlation between [131I]cG250 uptake and each individual parameter was determined in a multiple regression analysis. Additionally, the data were reanalysed after introducing arbitrary cut-off values for each parameter. If a sample showed expression of a parameter above the introduced threshold value, this sample fulfilled one condition. Subsequently, the Pearson correlation coefficients were calculated from [131I]cG250 uptake and the number of fulfilled conditions (0-3). All tumour samples with high [131I]cG250 uptake [> 0.1% of the injected dose per gram (ID g(-1))] showed high antigen expression (> 50%). However, not all samples with high antigen expression displayed high uptake. A statistically significant correlation between [131I]cG250 uptake and antigen expression was found (beta = 0.44, 0.69 and 0.74) in three out of four tumours analysed. Of the other determined parameters, no consistent correlation with [131I]cG250 uptake was found; only the percentage of viable tumour cells correlated significantly in two out of four tumours (beta = 0.80 and 0.26). Calculation of the Pearson correlation coefficients showed a statistically significant correlation between [131I]cG250 uptake and an increased number of fulfilled conditions in all tumours, indicating that each of the individual parameters contribute to the uptake of [131I]cG250. These observations indicate that high antigen expression is a prerequisite for high antibody uptake. However, regional differences in antibody uptake within a tumour cannot be explained by antigen expression alone.
Antibodies, Monoclonal↗
Increased interleukin-1alpha and interleukin-1beta production by macrophages of low-density lipoprotein receptor knock-out mice stimulated with lipopolysaccharide is CD11c/CD18-receptor mediated.
Immune mechanisms, including production of pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF), play an important role in early atherogenesis. The study of the mechanisms responsible for the increased cytokine production capacity of hypercholesterolemic hosts is therefore crucial for finding new strategies aimed to stop the development of atherosclerosis. We assessed the lipopolysaccharide (LPS)-induced cytokine production of macrophages from low-density lipoproteins (LDL)-receptor knock-out (LDLR-/-) mice, which have a seven- to ninefold higher plasma LDL concentration. Macrophages of LDLR-/- mice produced approximately twofold more IL-1alpha and IL-1beta in response to LPS when compared with macrophages of control mice (LDLR+/+). TNF-alpha synthesis was only slightly increased. Removal of CD14 by phospholipase C treatment of cells decreased cytokine production by 50% (IL-1) to 80% (TNF), but the differences between LDLR-/- and LDLR+/+ remained the same. In contrast, treatment of cells with anti-CD11c monoclonal antibody inhibited the IL-1alpha and IL-1beta production in LDLR-/- mice towards normal values, while no effect could be seen on TNF. In conclusion, LDLR-/- macrophages stimulated with LPS synthesize more IL-1alpha and IL-1beta than controls and this phenomenon is mediated by the CD11c/CD18 receptor.
Animals↗
In vivo expression of interleukin-1 receptors during various experimentally induced inflammatory conditions.
Systemically administered interleukin-1 (IL-1) has been shown to preferentially bind to IL-1 receptors (IL-1Rs) in inflammation. Using radiolabeled IL-1alpha and molecular methods to assess gene expression for these receptors, the in vivo behavior of these receptors was investigated in a number of experimental inflammatory conditions. The uptake of 125I-labeled IL-1alpha in inflammatory foci significantly correlated with the mRNA expression for the type I and type II IL-1Rs (P < .05). Type II IL-1R mRNA showed a greater increase in expression than type I IL-1R mRNA. In neutropenic mice, inflammatory lesions, which are devoid of granulocytes, significantly lower 125I-labeled IL-1alpha uptake (P < .001), and type II IL-1R mRNA expression (P < .005) was found. Thus, there is strong up-regulation of IL-1Rs at sites of focal inflammation. Of interest, this mainly involved the type II IL-1R on granulocytes, which is not involved in signal transduction.
Animals↗
Tumor retention of 186Re-MAG3, 111In-DTPA and 125I labeled monoclonal antibody G250 in nude mice with renal cell carcinoma xenografts.
UNLABELLED: In radioimmunotherapy of solid tumors substantial gain might be achieved by carefully selecting the radionuclide and the linker connecting it to the antibody. In contrast to 131I, radiometals such as 90Y and 111In may be retained in the tumor cell after internalization of the antibody, thereby enhancing the radiation dose to the tumor. The physical properties of 186Re with 1.08 MeV beta-emission (71%) and 137 keV gamma-emission (10%) seem ideal for radioimmunotherapy. In this study we investigated in nude mice with s.c. renal cell carcinoma xenografts the biodistribution and the retention in the tumor of 186Re-MAG3 labeled monoclonal antibody (mAb) G250 as compared to 111In-DTPA-G250, to 125I-G250 and to 131I-MN14 (non-specific control mAb). Radiolabeled antibody preparations were i.v. injected. Seventy two hours p.i. the biodistribution of the radiolabel was determined. Blood levels of all mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43% ID/g for 125I, 111In and 186Re respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3% ID/g), indicating tumor processing of mAb G250. Retention of 111In in the tumor was significantly higher than of 186Re and 125I whereas retention in the tumor of 186Re and 125I did not differ significantly. CONCLUSION: In contrast to other radiometals such as 111In and 90Y, 186Re is not retained in the tumor cell. Therefore 186Re has no additional advantage for radioimmunotherapy with respect to retention in the tumor.
Animals↗
The kinetics of radiolabelled interleukin-8 in infection and sterile inflammation.
Radiolabelled interleukin-8 (IL-8) is a promising agent for the imaging of infection and inflammation. Several experiments were performed to explore further the imaging potential of radiolabelled IL-8. IL-8 was radioiodinated via the Bolton-Hunter method. Rabbits with focal infection (Escherichia coli, Staphylococcus aureus) or sterile inflammation (zymosan) were injected intravenously with 18.5 MBq (0.5 mCi) of 123I-IL-8. In separate studies, rabbits were injected intravenously with 111In-granulocytes with or without 125I-IL-8. Gamma camera images were obtained at 5 min, 1, 4 and 8 h post-injection (p.i.). Biodistribution was determined at 8 h p.i. In all models, the biodistribution of 123I-IL-8 was characterized by rapid blood clearance and high uptake in infection and sterile inflammation. All foci could be clearly visualized within 4 h p.i. Ex vivo abscess-to-contralateral muscle ratios increased to 114.7+/-23.0 (E. coli), 52.3+/-24.5 (S. aureus) and 49.8+/-8.3 (zymosan) at 8 h p.i. In the circulation, most 123I-IL-8 was bound to erythrocytes. The abscess uptake of 125I-IL-8 reached high levels despite reduced migration of granulocytes towards the site of infection due to the anti-inflammatory activity of intravenously injected IL-8. IL-8 could be injected without induction of neutropenia at a dosage of 2 ng kg(-1). In conclusion, the characteristics of radiolabelled IL-8 for imaging of infection and sterile inflammation are highly encouraging and warrant further optimization for clinical application.
Animals↗
Dynamic distribution and dosimetric evaluation of human non-specific immunoglobulin G labelled with 111In or 99Tcm.
This study presents data on the dynamic distribution and dosimetry of 111In- and 99Tcm-labelled human non-specific immunoglobulin G (IgG), two recently developed radiopharmaceuticals for the detection of infection and inflammation. Five healthy volunteers were injected with 20-75 MBq 111In-IgG and seven patients were injected with 740 MBq 99Tcm-hydrazinonicotinamide derivative (HYNIC)-IgG. Blood samples, urine and feces were collected. Whole-body gamma camera imaging studies were performed. The activity in source organs was quantified using the conjugate view counting method and a partial background subtraction technique. Dosimetric calculations were performed using the MIRD technique. For 111In-IgG, the mean biological half-times in the blood were 0.90 and 46 h for the a- and b-phase, respectively. For 99Tcm-HYNIC-IgG, these half times were 0.46 and 45 h. For 111In-IgG, the mean cumulative urinary excretion in the first 48 h was 18% of the injected dose, while excretion in the feces was less than 2% of the injected dose. For 99Tcm-HYNIC-IgG, the whole-body retention was always 100% up to 24 h. The mean absorbed doses in the liver, spleen, kidneys, red marrow and testes from 111In-IgG were 0.8, 0.7, 1.2, 0.3 and 0.4 mGy MBq-1 respectively. The mean absorbed doses for 99Tcm-HYNIC-IgG to these organs were 16, 24, 15, 10 and 22 mu Gy MBq-1 respectively. The mean effective dose was 0.25 mSv MBq-1 and 8.4 mu Sv MBq-1 for 111In-IgG and 99Tcm-HYNIC-IgG respectively. In conclusion, the radiation absorbed doses for both 111In-IgG and 99Tcm-HYNIC-IgG are low and, therefore, these radiopharmaceuticals can be administered safely from a radiation risk perspective.
Adult↗
Technetium-99m labeled to human immunoglobulin G through the nicotinyl hydrazine derivative: a clinical study.
UNLABELLED: A novel method to label polyclonal human immunoglobulin G (IgG) with 99mTc through the nicotinyl hydrazine derivative (HYNIC) has shown promising results in the detection of experimental infection. In this study, 99mTc-labeled HYNIC-IgG was directly compared to (111)In-labeled diethylenetriaminepentaacetic acid (DTPA)-IgG in patients suspected of infectious or inflammatory disease. METHODS: Thirty-seven patients (22 women and 15 men; mean age = 54 yr, range = 17-78 yr) with 39 suspected infectious or inflammatory foci were prospectively studied. After administration of 740 MBq 99mTc-HYNIC-IgG, imaging was performed at 4 and 24 hr postinjection. To avoid cross-over activity, (111)In-DTPA-IgG was injected 24 hr after 99mTc-HYNIC-IgG and imaged at 4, 24 and 48 hr postinjection. The scintigraphic results were confirmed by microbiological, histological, radiological and clinical methods. RESULTS: Technetium-99m-HYNIC-IgG and (111)In-DTPA-IgG scintigraphy showed 100% concordancy. All 17 patients with proven infection or inflammation (19 foci, mainly localized in the locomotor system) had positive scintigraphic findings. No false-negative scintigrams were recorded. In three patients, the scintigrams were concordantly false-positive. As a result, the sensitivity and specificity of imaging infectious or inflammatory foci with 99mTc-HYNIC-IgG and (111)In-DTPA-IgG in these patients were 100% and 85%, respectively. CONCLUSION: Technetium-99m-HYNIC-IgG scintigraphy is equally as effective as (111)In-IgG scintigraphy for the detection of infection and inflammation. The apparent physical and logistic advantages of 99mTc over (111)In make 99mTc-HYNIC-IgG a promising new radiopharmaceutical for imaging infection and inflammation.
Bacterial Infections↗
Absolute organ activity estimated by five different methods of background correction.
UNLABELLED: Accurate absorbed dose estimates in radionuclide therapy require patient-specific dosimetry. In patient-based dosimetry, estimation of absolute organ uptake is essential. The methods used should be reasonably accurate as well as easy to perform in routine clinical practice. One of the major sources of uncertainty in quantification of organ or tumor activity from planar images is the activity present in the tissue surrounding the source. METHODS: To estimate organ activity as a function of organ-to-background activity concentration ratio, a cylindrical phantom, filled with 5.6 liters of water was used to simulate the abdomen of a patient. Two other cylinders of 150 ml each, representing the kidneys, were each filled with 19 MBq 99mTC and were positioned in the abdomen phantom. The phantom was imaged with a dual-head gamma camera with the kidneys placed at posterior depths of 1-, 5- and 10-cm at kidney-to-background activity concentration ratios of infinity, 10:1, 5:1 and 2:1. The conjugate view geometric mean counting method was used to quantify activity. Five methods for background correction were applied: (1) no correction; (2) conventional background correction (simple subtraction of the background counting rate from the source region counting rate); (3) Kojima method (background corrected for organ thickness and depth); (4) Thomas method (analytical solution); and (5) Buijs method (background corrected for organ and total-body thickness). RESULTS: Since the results were identical for both kidneys, only the left kidney activity measurements are presented. The accuracy of the five background correction methods is given as the percentage difference between the actual and measured activity in the left kidney. For Method 1, the percentage difference ranged from 2% with an infinite kidney-to-background activity concentration ratio to +413% with a 2:1 ratio. For Method 2, these values ranged from -1% to -80%, for Method 3 from +11% to -18%, for Method 4 from -2% to +120% and for Method 5 from -4% to +39%. CONCLUSION: Even though quantitative SPECT is the most rigorous method for activity quantification in conditions of low organ-to-background activity concentration ratio, planar scintigraphy can be applied accurately if appropriate attention is paid to background correction. Using relatively simple background subtraction methods, the quantitative planar imaging technique can result in reasonably accurate activity estimates (Methods 3 and 5). The use of Kojima's method is preferable, especially at very low source-to-background activity concentration ratios.
Humans↗
Technetium-99m-labeled liposomes to image experimental colitis in rabbits: comparison with technetium-99m-HMPAO-granulocytes and technetium-99m-HYNIC-IgG.
UNLABELLED: Scintigraphic techniques are routinely used for the evaluation of the extent and severity of inflammatory bowel disease. Currently, the radiopharmaceutical of choice is 99mTc-hexamethyl propyleneamine oxime (HMPAO)-leukocytes. We studied the imaging potential of two recently developed 99mTc-labeled agents, polyethylene glycol (PEG)-coated liposomes and hydrazinonicotinate (HYNIC) IgG, in a rabbit model of acute colitis, and compared them with that of 99mTc-labeled, granulocyte-enriched (>90%), white blood cells. METHODS: Acute colitis was induced in rabbits by retrograde instillation of trinitrobenzene sulfonic acid. After 48 hr, 37 MBq of each radiopharmaceutical was administered intravenously. Gamma camera images were taken at 0, 1, 2, 4, 10 and 24 hr. At 4 and 24 hr postinjection, groups of rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. For each affected 5-cm segment, the colitis index (CI, affected-to-normal-colon-uptake ratio) was calculated and correlated to the macroscopically scored severity of inflammation. RESULTS: All three agents visualized the colitis lesions within 1 hr postinjection. The CI correlated with the severity of the abnormalities. With increasing severity, the CI at 4 hr postinjection for liposomes was 3.89+/-0.73, 4.41+/-0.47 and 5.76+/-0.65; for IgG 1.67+/-0.08, 3.92+/-0.44 and 6.14+/-0.65; and for granulocytes 2.90+/-0.09, 6.15+/-0.96 and 9.36+/-3.35. For liposomes, the CI further increased during 24-hr postinjection to 6.56+/-0.84, 8.50+/-0.53 and 10.61+/-1.34, respectively. The CI for the other two agents did not change significantly with time. CONCLUSION: In this rabbit model, 99mTc-labeled granulocytes, IgG and liposomes all rapidly visualized colonic inflammation. Granulocytes and liposomes showed the highest CI. Technetium-99m-labeled PEG-liposomes may be an attractive alternative for labeled leukocytes to image inflammatory bowel disease, because they can be prepared off the shelf and no handling of blood is required.
Animals↗