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F H Corstens

Publications and source records attributed to F H Corstens.

At least 19 recordsLinked to original sources

What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. PATIENTS, METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). RESULTS: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n = 143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n = 44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS: TcTUsbased determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.

Dose-Response Relationship, Radiation↗

[Subclinical hypothyroidism; the start of a clinical trial into the usefulness of treatment with radioactive iodine].

Subclinical hyperthyroidism is defined as the presence of serum free thyroxine (T4) and triiodothyronine (T3) levels within the reference range and a reduced serum thyrotrophin (TSH) level. Evidence is accumulating that it has important clinical effects. Randomised clinical trials are needed to answer the question whether or not treatment of subclinical hyperthyroidism prevents cardiac problems, especially atrial fibrillation, and preserves bone mineral density. A randomised, Dutch multicentre trial has recently been started. Its goal is to study whether radioiodine treatment prevents the development of atrial fibrillation and prevents decreases in bone mineral density.

Atrial Fibrillation↗

Tc-99m-labeled C5a and C5a des Arg74 for infection imaging.

UNLABELLED: The complement anaphylatoxin C5a and its natural metabolite C5a des Arg(74) (C5adR) are involved in several stages of the inflammatory process. Both act on a common receptor expressed on different cell types, including neutrophils and monocytes. The receptor binding affinity of C5a is in the nanomolar range and exceeds that of C5adR by 1-2 orders of magnitude. The biologic potency of C5a is considerably higher than that of C5adR. Here we tested both proteins labeled with (99m)Tc for imaging of infection. METHODS: The proteins were labeled with (99m)Tc via the hydrazinonicotinamide (HYNIC) chelator. The preparations were tested for imaging of infection in a rabbit model of intramuscular infection. Biodistribution of the radiolabel was determined by gamma-camera imaging and by counting dissected tissues at 5 h p.i. RESULTS: C5a and C5adR showed in vivo abscess uptakes of 0.12 and 0.025%ID/g, abscess/muscle ratios of 76 and 14, abscess/blood ratios of 9.1 and 2.6, and ROI derived target-to-background ratios of 5.9 and 2.1, respectively at 5 h p.i. CONCLUSION: For infection imaging (99m)Tc-labeled C5a showed excellent in vivo characteristics. However, C5a is a very bioactive protein, impeding its clinical use as an infection imaging agent. The naturally occurring partial agonist C5adR has less biological effect but showed suboptimal imaging characteristics. The present study showed that for adequate localization of a receptor binding ligand affinities for the receptor in the nanomolar range are required.

Animals↗

Microscopic localization of PEG-liposomes in a rat model of focal infection.

In the present study the microscopic localization of polyethylene glycol (PEG) liposomes in infected tissues was studied with both light microscopy (LM) and transmission electron microscopy (TEM) in rats with focal intramuscular Staphylococcus aureus infection. PEG-liposomes containing colloidal gold were prepared and injected intravenously in rats with focal S. aureus infection and tissues were dissected at 24 h post injection. Sections were cut and liposomes were visualized for microscopic evaluation using silver enhancement. Uptake of PEG-liposomes was visualized by both scintigraphy and LM in the abscess, liver and spleen. In the infected area, the liposomes were mainly found in the vicinity of blood vessels. TEM showed that the liposomes were localized in the macrophages and to a lesser extent in endothelial cells in the infectious tissue. In the liver, the liposomes appeared mainly localized in Kupffer cells. In the spleen, uptake was only seen in cells of the red pulp and in cells around the central arteries. Our microscopic observations indicate that uptake and retention of PEG-liposomes in the infectious focus is a result of enhanced extravasation due to increased vascular permeability and subsequent phagocytosis of PEG-liposomes by macrophages in the infected tissue.

Abscess↗

Radiopharmaceuticals for scintigraphic imaging of infection and inflammation.

Scintigraphic imaging of infection and inflammation is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. Most infectious and inflammatory foci can be visualized accurately with radiolabeled autologous leukocytes. However, preparation of this radiopharmaceutical is laborious and requires the handling of potentially contaminated blood. Nowadays, a few radiopharmaceuticals are available that could replace radiolabeled leukocytes, such as: 67Ga-citrate, 99mTc-IgG and 99mTc-labeled antigranulocyte antibody preparations. Furthermore, various agents labeled with 99mTc are currently developed for this application: chemotactic peptides, cytokines and liposomes. Here, the characteristics and the diagnostic potential of established and experimental radiopharmaceuticals for infection and inflammation imaging are reviewed.

Antibodies↗

Bone mineral density and quantitative ultrasound parameters in patients with Klinefelter's syndrome after long-term testosterone substitution.

Klinefelter's syndrome (KS) is a common sex chromosomal disorder associated with androgen deficiency and osteoporosis. Only few bone mineral density (BMD) and no quantitative ultrasound (QUS) data are available in these patients after long-term testosterone replacement therapy. We examined in a cross-sectional study 52 chromatin-positive KS patients aged 39.1 +/- 12.4 years (mean +/- SD). Patients had been treated with oral or parenteral androgens for 9.2 +/- 8.2 years (range 1-32 years). Areal BMD and bone mineral apparent density (BMAD, i.e., estimated volumetric BMD) at the lumbar spine, total hip and femoral neck were determined by dual-energy X-ray absorptiometry. BMD T-scores in the patient group were calculated based on three different North American reference databases. The QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus using an ultrasound imaging device (UBIS 3000) and were compared with QUS results in a sex-, age- and height-matched control group. QUS T-scores were calculated based on the results of QUS measurements in 50 normal Dutch men between the ages of 20 and 30 years. QUS and BMD results in the KS patient group were compared. Overall, based on the three reference databases, 46% and 63% of the KS patients had a T-score between -1 and -2.5 and a further 10% and 14% had a T-score < or = -2.5 at the total hip and/or lumbar spine, as measured by areal BMD or BMAD, respectively. Thirty-nine percent of the KS patients had a T-score between -2.5 and -1, while 2% had a T-score < or = -2.5 for BUA and/or SOS. BUA (77.7 +/- 15.0 dB/MHz) and SOS (1518.8 +/- 36.5 m/s) were significantly lower in the KS patients than in age- and height-matched controls (87.1 +/- 17.8 dB/MHz, p < 0.005, and 1536.5 +/- 42.5 m/s, p < 0.05). Correlation coefficients between the QUS parameters and areal BMD (0.28 to 0.37) or BMAD (0.27 to 0.46) were modest. ROC analysis showed that discrimination of a BMD or BMAD T-score < or = -2.5 with either BUA or SOS was not statistically significant. Although a limitation of our study is that direct comparison of BMD and QUS T-scores is not possible because in the control group in which QUS parameters were determined no BMD measurements were performed, we conclude that despite long-term testosterone replacement therapy, a considerable percentage of patients with KS had a BMD T-score < -1 or even < or = -2.5, based on different North American reference databases. This percentage was even higher for BMAD. QUS parameters were also low in the KS patient group when compared with Dutch control subjects. QUS parameters cannot be used to predict BMD or BMAD in KS patients.

Adult↗

Imaging infection/inflammation in the new millennium.

In the closing half of the past century a wide variety of approaches were developed to visualise infection and inflammation by gamma scintigraphy. Use of autologous leucocytes, labelled with indium-111 or technetium-99m, is still considered the "gold standard" nuclear medicine technique for the imaging of infection and inflammation. However, the range of radiopharmaceuticals used to investigate infectious and non-microbial inflammatory disorders is expanding rapidly. Developments in protein/peptide chemistry and in radiochemistry should lead to agents with very high specific activities. Recently, positron emission tomography with fluorine-18 fluorodeoxyglucose has been shown to delineate infectious and inflammatory foci with high sensitivity. The third millennium will witness a gradual shift from basic (non-specific) or cumbersome, even hazardous techniques (radiolabelled leucocytes) to more sophisticated approaches. Here a survey is presented of the different approaches in use or under investigation.

Animals↗

Radioimmunotherapy of B-cell non-Hodgkin's lymphoma.

In the past decade, several new antibody-based therapies - using either radiolabelled or unlabelled monoclonal antibodies - have become available for the treatment of patients with refractory or recurrent non-Hodgkin's lymphoma (NHL). Unlabelled monoclonal antibodies (mAbs) kill lymphoma cells by activating host immune effector mechanisms, or by inducing apoptosis. These mAbs can also be used to guide radionuclides to the lymphoma. This radioimmunotherapy (RIT) has been studied with various nuclides (131I, 90Y, 67Cu and 186Re) and with various mAbs. In this review the radionuclides, methods of dosing and recent RIT studies in patients with B-cell NHL are reviewed. Most of these studies demonstrate that RIT is an effective new treatment modality for NHL.

Antibodies, Monoclonal↗

Animal models of infection and inflammation and their role in experimental nuclear medicine.

In this review, basic aspects of nuclear medicine are described. One of the fields of research in nuclear medicine is the development of new radiopharmaceuticals for imaging infection and inflammation in humans. For this development, animal models are identified and modified to needs of a particular research question. In this review, a wide variety of models that are available in our laboratory are presented and the strengths and pitfalls are discussed.

Animals↗

The effect of molecular weight on nonspecific accumulation of (99m)T-labeled proteins in inflammatory foci.

UNLABELLED: Although several proteins have been proposed and tested for scintigraphic detection of infection, the most optimal characteristics of a protein for this application have not yet been determined. Molecular weight (MW) of the protein, its charge, shape, carbohydrate content, characteristics of the radionuclide and receptor interactions are factors that could affect the in vivo behavior of the infection imaging agent. The effect of molecular weight on nonspecific accumulation of (99m)Tc-labeled proteins in inflammatory foci was studied in a rat model. METHODS: Eleven proteins whose MWs ranged from 2.5 kDa up to 800 kDa were labeled with (99m)Tc using the hydrazinonicotinamide (HYNIC) chelator. Rats with S. aureus infection were injected i.v. with 15 MBq (99m)Tc-labeled protein. Gamma camera images were acquired and biodistribution of the radiolabel was determined ex vivo. RESULTS: From biodistribution data no significant correlation was found between abscess uptake and molecular size of the (99m)Tc-labeled proteins that were studied. Fast blood clearance with predominant uptake in liver and spleen was found for the largest proteins (MW 669 kDa-800 kDA). For proteins of intermediate size (MW 66 kDa -206 kDa) we found relatively slow blood clearance with relatively moderate uptake in liver and spleen. For smaller proteins (MW 2.5 kDa -29 kDa) rapid blood clearance with predominant kidney uptake was observed. The abscess uptake of the (99m)Tc-labeled proteins (%ID/g, 24 h p.i.) was highest for serum proteins IgG and BSA. Abscess uptake correlated well with blood levels: r = 0.95 and 0.84 at 4 and 24 h respectively (P < 0.005). The abscess-to-muscle ratios varied from 2.1 to 17.8 at 24 h p.i. with highest values for alpha-2 macroglobulin (MW 725 kDa) and the intermediate sized proteins (MW 66-206 kDa). Gamma camera imaging showed localization of all radiotracers at the site of infection with abscess-to-background ratios (A/B) ranging from 1.4 to 7.0 (IgG) at 20 h p.i. The serum proteins IgG and BSA showed highest blood levels and best infection imaging characteristics. CONCLUSION: Not molecular weight but blood residence time is the principal factor that determines localization of a nonspecific tracer protein in infectious foci. The ideal nonspecific infection imaging agent is a protein with a long circulatory half-life. From the proteins tested here IgG and albumin showed the best characteristics for an infection imaging agent.

Animals↗

Radiopharmaceuticals to image infection and inflammation.

Scintigraphic imaging of infection and inflammation is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. Most infectious and inflammatory foci can be visualized accurately with radiolabeled autologous leukocytes. However, the preparation of this radiopharmaceutical is laborious and requires the handling of potentially contaminated blood. A few radiopharmaceuticals are available that could be used instead of radiolabeled leukocytes to scintigraphically visualize infectious and inflammatory foci, such as 67Ga-citrate and 99mTc-labeled antigranulocyte antibody preparations. Various agents labeled with 99mTc are currently developed for this application. Most of these newly developed agents are ligands that bind receptors on white blood cell subpopulations, ie, monoclonal antibodies, chemotactic peptides, and cytokines. Furthermore, agents are developed that potentially could distinguish between infection and nonmicrobial inflammation. In addition, 18F-fluorodeoxyglucose positron emission tomography imaging was proposed to visualize inflammatory foci when a high spatial resolution is required. In this article, the characteristics and diagnostic potential of established and experimental radiopharmaceuticals for infection and inflammation imaging are reviewed.

Animals↗

Nuclear medicine techniques for the diagnosis and therapy of prostate carcinoma.

Nuclear medicine techniques play an important role in (re)staging and treatment of prostate carcinoma patients. These techniques are reviewed in this paper. For many years, bone scanning has been a valuable tool for the evaluation of bone metastases. Although utilized in a more refined way since the introduction of serum prostate-specific antigen (PSA) measurement, it is still the procedure of choice in patients with higher-grade or higher-stage tumors and elevated or rising PSA levels. Labeled monoclonal antibodies have been found to have some utility in the clinic for the evaluation of disseminated malignant prostate disease and position emission tomography holds promise for the metabolic characterization of prostate cancer. Several agents are available for radionuclide therapy for bone pain palliation in patients with metastasis, improving pain with minimal side effects or discomfort to the patient. Nuclear medicine techniques in prostate carcinoma are far from obsolete. On the contrary, they are evolving and offer unique opportunities for the management of these patients. The bone scan remains useful in well-defined stages of disease, and palliative therapeutic options are evolving. At present, monoclonal antibodies and PET are not very useful in daily clinical practice.

Antibodies, Monoclonal↗

Pretreatment with recombinant human TSH changes the regional distribution of radioiodine on thyroid scintigrams of nodular goiters.

In a recent study, we demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h thyroid radioactive iodine uptake in patients with nodular goiter. The purpose of the present study was to investigate whether rhTSH pretreatment induces changes in the regional distribution of radioiodine as visualized on thyroid scintigrams in these patients. Anterior planar thyroid 123I scintigrams were obtained in 26 patients with a nodular goiter (23 women and 3 men; age, 62 +/- 9 yr, mean +/- SD; thyroid weight, 165 +/- 72 g) 24 h after administration of a diagnostic dose of radioiodine. All patients were studied twice: first, without rhTSH pretreatment (baseline study), and second, after an im injection of 0.01 mg (n = 10) or 0.03 mg rhTSH (n = 16), given 24 h before radioiodine administration (rhTSH study). For quantification of regional differences in radioiodine uptake, a region of interest method was used. Upon visual inspection, baseline scintigrams showed a heterogeneous uptake of radioiodine. In general, rhTSH scintigrams also showed heterogeneous radioiodine uptake. In some patients, the distribution of radioiodine in the rhTSH scintigram was considerably more homogeneous than in the baseline scintigram. In a few patients, originally "cold" areas had changed into "hot" ones, whereas originally hot areas had changed into cold ones. Quantification of regional radioiodine uptake showed that pretreatment with rhTSH caused a larger increase in radioiodine uptake in relatively cold areas and a smaller increase in radioiodine uptake in relatively hot areas, compared with the increase in radioiodine uptake in the entire thyroid. In patients with a baseline serum TSH level of 0.5 mU/liter or lower, the increase in radioiodine uptake in relatively cold areas was significantly larger than in patients with a baseline serum TSH level higher than 0.5 mU/liter. In conclusion, a single, low dose of rhTSH not only doubled 24-h radioactive iodine uptake but also caused a more homogeneous distribution of radioiodine within the thyroid gland in patients with a nodular goiter by stimulating radioiodine uptake in relatively cold areas more than in relatively hot areas. This was most marked in patients with a low baseline serum TSH level. Our data suggest that pretreatment with rhTSH may improve the efficacy of radioiodine treatment for volume reduction of nodular goiters, especially in patients with a low baseline serum TSH level.

Aged↗

Specific and rapid scintigraphic detection of infection with 99mTc-labeled interleukin-8.

UNLABELLED: Interleukin-8 (IL-8) is a chemotactic cytokine involved in activation and recruitment of neutrophils to areas of infection. In our previous studies in rabbits we tested 123I-labeled IL-8 for its potential to image infections and showed that IL-8 rapidly and efficiently accumulated in infectious foci. However, labeling of IL-8 with 123I is costly and laborious and the specific activity of the preparation was low. In this study IL-8 was labeled with 99mTc through the hydrazinonicotinamide (HYNIC) chelator. METHODS: The leukocyte receptor-binding capacity of the preparation was determined in vitro. Rabbits with Escherichia coli abscesses were injected intravenously with 7 MBq 99mTc-HYNIC-IL-8. Biodistribution of the radiolabel was determined by gamma camera imaging and tissue counting at 8 h after injection. 99mTc-HYNIC-lysozyme was used as a size-matched control. RESULTS: The leukocyte receptor-binding capacity of the 99mTc-HYNIC-IL-8 preparation was preserved as determined in vitro, but labeling efficiency was modest with a specific activity of 3 MBq/microg. 99mTc-HYNIC-IL-8 accumulated rapidly in the abscess up to 0.33 +/- 0.06 percentage injected dose per gram (%ID/g) at 8 h after injection (vs. 0.025 +/- 0.003 %lD/g for 99mTc-HYNIC-lysozyme). Total uptake in the abscess was 4.9 +/- 0.7 %ID (vs. 0.44 +/- 0.05 %ID for 99mTc-HYNIC-lysozyme). Abscess-to-contralateral muscle ratios increased up to 127 +/- 23 (compared with 6.7 +/- 1.1 for 99mTc-HYNIC-lysozyme) and abscess-to-blood ratios increased to 11.9 +/- 2.2 (0.24 +/- 0.03 for 99mTc-HYNIC-lysozyme). The radiolabel was excreted renally, with a retention in the kidneys of 28 %ID. Gamma camera imaging rapidly visualized the abscess from 1 h after injection onward, with abscess-to-background ratios improving with time up to 22 at 8 h after injection (vs. 2.7 for 99mTc-HYNIC-lysozyme), as determined by quantitative analysis of the images. Most important, only a transient (30 min) moderate drop of leukocyte counts and no leukocytosis were observed after injection of an imaging dose of 99mTc-HYNIC-IL-8. CONCLUSION: IL-8 can be labeled with 99mTc using HYNIC as a chelator. By this method the leukocyte receptor-binding capacity is preserved. The preparation allows rapid visualization of infection in a rabbit model with high target-to-background ratios. The mild transient drop of leukocyte counts and the absence of leukocytosis suggest that 99mTc-HYNIC-IL-8 may be used as an imaging agent with only mild and transient side effects.

Abscess↗

Rapid imaging of experimental colitis with (99m)Tc-interleukin-8 in rabbits.

UNLABELLED: Radiolabeled autologous leukocytes (WBCs) are the gold standard for imaging inflammatory bowel disease (IBD). For the rapid and adequate management of patients with IBD, there is need for a new agent at least as good as radiolabeled WBCs, but easier to prepare and without its inherent risks. In this study, the potential of interleukin-8 (IL-8) labeled with (99m)Tc using hydrazinonicotinamide (HYNIC) to image IBD was investigated in a rabbit model of acute colitis and compared with that of (99m)Tc-HMPAO-labeled granulocytes. METHODS: In rabbits with chemically induced acute colitis, inflammatory lesions were scintigraphically visualized after injection of either IL-8 or purified granulocytes, both labeled with (99m)Tc. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. Four hours after injection, the rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. The dissected colon was imaged and the inflammatory lesions were scored macroscopically. For each affected colon segment, the colitis index (affected colon-to-normal colon uptake ratio, CI) was calculated and correlated with the macroscopically scored severity of inflammation. RESULTS: Both agents visualized the colitis within 1 h after injection. (99m)Tc-HYNIC-IL-8 images of the colonic abnormalities were more accurate and the intensity of uptake in the affected colon continuously increased until 4 h after injection, whereas no further increase 1 h after injection was noticed scintigraphically for (99m)Tc-HMPAO-granulocytes. The absolute uptake in the affected colon was much higher for IL-8 than for the radiolabeled granulocytes with the percentage injected dose per gram (%ID/g) 0.41 +/- 0.04 %ID/g and 0.09 +/- 0.05 4 %ID/g h after injection, respectively. With increasing severity, the CI at 4 h after injection for (99m)Tc-HYNIC-IL-8 was 4.4 +/- 0.6, 13.5 +/- 0.5, and 25.8 +/- 1.0; for granulocytes, the CI at 4 h after injection was 1.5 +/- 0.1, 3.4 +/- 0.2, and 6.4 +/- 0.5, respectively. The CI correlated with the severity of the inflammation (r = 0.95, P < 0.0001 for IL-8; r = 0.95, P < 0.0001 for granulocytes). CONCLUSION: Within 1 h after injection, visualization of the extent of colonic inflammation in vivo was possible with (99m)Tc-HYNIC-IL-8 and (99m)Tc-HMPAO-granulocytes. Within 2 h after injection, (99m)Tc-IL-8 allowed a good evaluation, and within 4 h after injection, a meticulous evaluation of the severity of IBD. Although (99m)Tc-HMPAO-granulocytes were able to delineate the extent of IBD within 2 h after injection, an accurate estimation of severity of inflammation was not possible. (99m)Tc-HYNIC-IL-8 is an inflammation-imaging agent that showed promising results in this study. (99m)Tc-IL-8 can be prepared off-the-shelf and yields excellent imaging with high target-to-background ratios.

Acute Disease↗

Factors affecting the accelerated blood clearance of polyethylene glycol-liposomes upon repeated injection.

Previously, we showed that long-circulating polyethylene glycol (PEG)-liposomes are cleared rapidly from the circulation when injected repeatedly in the same animal. In this article, we describe the effects of PEG-coating, the circulation time, the lipid dose, and the presence of encapsulated doxorubicin on the pharmacokinetics upon repeated injection in rats. Furthermore, the role of liver and splenic macrophages was investigated. Liposomes without PEG-coating also showed the so-called "enhanced clearance effect": blood levels at 4 h post injection decreased from 62.8 +/- 13.7% of injected dose (%ID) after the first injection to 0.54 +/- 0.21%ID after the second injection. This decrease was independent of the circulation time of the first dose. Decreasing the first lipid dose of PEG-liposomes to 0.05 micromol/kg still led to enhanced clearance of a second dose of 5 micromol/kg. No changes in pharmacokinetics were observed when the second dose was 50 micromol/kg. When hepatosplenic macrophages were depleted, no enhanced clearance of repeated liposome injections was observed. A dose of doxorubicin containing PEG-liposomes (Doxil), injected 1 week after injection of empty PEG-liposomes, was cleared rapidly from the circulation in rats. Our results indicate that hepatosplenic macrophages play an essential role in the enhanced clearance effect and that the change in pharmacokinetic behavior upon repeated injection is a general characteristic of liposomes, unrelated to the presence of PEG. Therefore, these findings may have a considerable impact on the clinical application of liposomal formulations that are administered repeatedly.

Animals↗

New concepts in infection/inflammation imaging.

Although autologous leukocytes, labelled with 111In or 99mTc, is still considered the "gold standard" nuclear medicine technique to image infection and inflammation, there is a great need for a less cumbersome and less hazardous approach. Over the last few decades the range of radiopharmaceuticals to investigate infectious and non-microbial inflammatory disorders is vastly expanding. Radiolabelled monoclonal antibodies and antibody-fragments, radiolabelled chemotactic peptides and cytokines, and radiolabelled antibiotics are promising new approaches in the field of nuclear medicine. Recently, positron emission tomography (PET) with 18FJDG has been introduced and has been shown to delineate infectious and inflammatory foci with high sensitivity. Here, a survey is presented of the different approaches in use or under investigation.

Animals↗