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Biomedical subjects

F H Corstens

Publications and source records attributed to F H Corstens.

At least 127 records · Page 7Linked to original sources

Effect of the route of administration on the biodistribution of radioiodinated OV-TL 3 F(ab')2 in experimental ovarian cancer.

The effect of the route administration on the distribution of radioiodinated OV-TL 3 F(ab')2 was studied in Balb/c female mice with intraperitoneal or subcutaneous ovarian carcinoma xenografts. In the intraperitoneal tumour model in which both ascites and solid tumour deposits were present, intraperitoneal administration resulted in a lower estimated radiation dose to blood as compared with intravenous administration. In this model normalization to equal estimated radiation doses to blood for both routes of administration indicated that a twice as high estimated radiation dose can be guided to solid intraperitoneal tumour deposits following intraperitoneal administration. Evacuation of ascitic tumour cells prior to monoclonal antibody injection further increased the estimated radiation dose to solid intraperitoneal tumour deposits following intraperitoneal delivery. Following simultaneous intravenous and intraperitoneal injection of the monoclonal antibody, tissue uptake showed no relevant differences in the subcutaneous tumour model. Overall, the intraperitoneal route of administration was found to be the best choice for therapeutic delivery of iodine-131 labelled monoclonal antibodies.

Animals↗

Decreased kidney uptake of technetium-99m-labelled Fab' fragments in ovarian carcinoma bearing nude mice using a cleavable chelator.

A new 99mTc labelling method using a cleavable chelator, RP-1, was developed. In this study Balb/c mice with ovarian carcinoma xenografts received various Fab' fragments labelled with 99mTc either directly or via RP-1. Kidney uptake was significantly lower for the RP-1 linked conjugates. Tumour uptake showed no significant differences between RP-1 conjugates and directly labelled preparations. In conclusion, with the use of the cleavable linker RP-1, kidney uptake can be reduced significantly resulting in a lower radiation dose to the kidneys.

Animals↗

Is somatostatin receptor scintigraphy suited to detection of acute infectious disease?

Fast and accurate delineation of acute infectious foci is very important for adequate management of patients. All currently available scintigraphic techniques require a relatively long timespan between referral to the nuclear medicine department and final diagnosis. Small peptides that bind to receptors on cells in the infectious focus might improve the diagnostic possibilities. Since activated leukocytes express somatostatin receptors, 111In-octreotide, a somastostatin analogue, was tested for its usefulness in detecting acute infection in rats with a calf muscle infection caused by Staphylococcus aureus. 111In-octreotide was compared with the much larger protein 111In-labelled human nonspecific immunoglobulin G (111In-IgG). As early as 0.5 h after injection, the 111In-octreotide uptake in the abscess was significantly lower than that of 111In-IgG. Moreover, no 111In-octreotide retention in the abscess over time was noted. In conclusion, somatostatin receptor imaging does not allow scintigraphic detection of an acute infectious lesion. The uptake in an abscess is relatively poor compared to 111In-IgG.

Abscess↗

Magnetic resonance imaging for volume estimation of large multinodular goitres: a comparison with scintigraphy.

As a result of increasing interest in non-surgical treatment for the reduction of goitre size the use of magnetic resonance (MR) imaging for volume estimation of large multinodular goitres was evaluated in 20 patients (three males and 17 females; age 61 +/- 21 years) with a multinodular goitre larger than 100 ml. In addition, MR measurements were compared with scintigraphic (SC) volume estimations. Intraobserver coefficient of variation (CV) of MR measurements was 2.2 +/- 2.0% (Observer 1) and interobserver CV 4.1 +/- 2.2% (Observers 1 and 2). In all 20 patients signs of mechanical complications were shown on MR images. For SC measurements intraobserver CV was 7.5 +/- 5.7% (Observer 3) and 5.4 +/- 5.1% (Observer 4). Interobserver CV was 10.1 +/- 6.1%. The correlation between measurements with both methods was not strong (r = 0.665) and the resulting CV was 17.3 +/- 14.2%. Underestimation of SC volumes could not be explained by the presence of cysts on the surface of the thyroid. It is concluded that MR imaging can be used for in vivo thyroid volume estimation in large multinodular goitres. The high precision of MR measurements makes this technique potentially useful for the evaluation of thyroid growth and non-surgical treatment for reducing goitre size. Scintigraphic volume measurements do not suffice for this purpose. An additional advantage of MR imaging is the detailed anatomical information it provides with regard to mechanical complications of large goitres.

Adult↗

Early detection of post-transplant pancreatic graft dysfunction with technetium-99m-HMPAO scintigraphy.

We present two cases of compromised pancreatic graft perfusion on a routine 99mTc-HMPAO-scan. The radiopharmaceutical, hexamethylpropyleneamine oxime (HMPAO), labeled with 99mTc-provided high-quality scintigraphic images of transplanted pancreatic grafts. Findings were compared with subsequently performed x-ray digital subtraction angiographs. Pathological examination of both resected grafts revealed venous thrombosis in one case and graft pancreatitis in the other case of disturbed graft perfusion on a 99mTc-HMPAO-scan. While 99mTc-HMPAO scans of pancreatic grafts are not specific for early thrombosis, they seem to be a helpful tool in diagnosing pancreatic dysfunction in general, necessitating further diagnostic steps to elucidate the specific cause.

Adult↗

[Compared to whole body scanning thyroglobulin assay is reliable in the follow-up of thyroidectomized patients with thyroid carcinoma].

OBJECTIVE: To determine whether it is reliable to do thyroglobulin measurements during thyroid hormone substitution (Tg ON) alone or whether it is also necessary to do 131I total body scanning (TBS) and Tg measurements after withdrawal of thyroid hormone substitution (Tg OFF) in the follow-up of patients with differentiated thyroid carcinoma. DESIGN: Retrospective. SETTING: University Hospital Nijmegen. METHODS: 202 Patients (151 females and 51 males, mean age 50.6 years) with differentiated thyroid carcinoma were examined in the period 1970-90. All patients had undergone total thyroidectomy and if necessary 131I ablation. 27 Patients with Tg antibodies were excluded (13.4%). In 175 patients Tg OFF levels were compared with TBS and clinical and radiological data. In 81 of them Tg ON levels were also compared. RESULTS: Specificity of Tg OFF and Tg ON measurement was 83 and 88%. Sensitivity of Tg OFF and Tg ON measurement was 100 and 92%. In detecting local residual thyroid tissue Tg OFF was superior to Tg ON. In detecting metastases Tg OFF and Tg ON were both superior to TBS. CONCLUSION: In the follow-up of patients with differentiated thyroid carcinoma it is reliable to do Tg measurements during thyroid hormone suppression. When Tg ON is detectable (> 3 pmol/l) TBS and Tg OFF measurement and if necessary further investigations have to be performed.

Adolescent↗

Long-term results of two schedules of radioiodine treatment for toxic multinodular goitre.

The long-term effects of two schedules of radioiodine therapy in patients with toxic multinodular goitre were evaluated. Forty-five patients (group A) were treated with low doses and 58 patients (group B) with calculated doses adjusted for thyroid weight (1.85-3.70 MBq/g) and radioactive iodine uptake. Follow-up (mean +/- SEM) was 4.3 +/- 0.2 years and 5.2 +/- 0.3 years, respectively (P > 0.1). At the end of follow-up, hyperthyroidism was successfully reversed in 73% (group A) and 88% (group B). In each group, hypothyroidism was present in 7%. The total dose per gram of thyroid tissue was not significantly different in groups A and B (2.1 +/- 0.2 vs 2.7 +/- 0.2 MBq/g). However, for patients treated with calculated doses the number of 131I administrations was significantly lower (1.3 +/- 0.1) than for patients treated with low doses (2.2 +/- 0.2), and the percentage of patients who were adequately treated with a single dose was more than twice as high (66% in group B versus 27% in group A). Euthyroidism was reached within a significantly shorter time after treatment with calculated doses (median time 0.6 years in group B vs 1.5 years in group A; life table analysis). It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a low risk of post-treatment hypothyroidism and that calculated (higher) doses appear to be preferable to low doses.

Adult↗

Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content.

The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval -36.0% to -8.1%) and cortical (-24.8%, 95% confidence interval -39.3% to -10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval -27.1% to -4.2%), but not the diaphyseal (-3.9%, 95% confidence interval -14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.

Absorptiometry, Photon↗

Measurement of mandibular bone density ex vivo and in vivo by dual-energy X-ray absorptiometry.

Severe bone resorption is a vexing clinical problem, especially in patients without teeth. To study resorption in vivo, measurements of bone mineral density (BMD) of the mandible of both patients with and without teeth are needed. Using a Hologic QDR-1000 bone densitometer designed to measure lumbar spine and hips, ex vivo and in vivo measurements were made in selected areas of the mandible. The mandible was positioned such that the X-ray beam was perpendicular to its sagittal plane. In this way the beam hits first one half of the mandible and then the other. The reproducibility--expressed as coefficient of variation--of the ex vivo measurements was 0.5%. For in vivo measurements this coefficient was 3%. The method used for mandibular BMD would make it possible to define an average BMD in several categories of the normal population and of patients, and to compare bone density in the mandible with that in the axial and perpendicular skeleton. Improvement may be obtained by repeating the measurement. The entrance dose per scan is low, equalling that of one bitewing/radiograph.

Absorptiometry, Photon↗

Radioimmunoconjugates in the detection of infection and inflammation.

Various nuclear medicine techniques are widely used to image foci of infection and inflammation. Among the relatively new radiopharmaceuticals for this purpose are radioimmunoconjugates such as labeled murine monoclonal antigranulocyte antibodies and labeled human polyclonal nonspecific immunoglobulin G. This article reviews some background information, mechanism of action, side effects, biodistribution, kinetics, results of clinical studies, and dosimetry of several radioimmunoconjugates both of murine monoclonal and human polyclonal origin. The efficacy of these agents has been demonstrated in a variety of clinical conditions. Radiolabeled immunoconjugates may emerge as convenient alternatives to the present technique of choice: in vitro blood cell labeling techniques with their inherent problems and risks.

Humans↗

Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity.

BACKGROUND: Generalised osteoporosis is often described in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate disease related determinants of bone mineral density (BMD) in patients with RA. METHODS: Subjects were selected from a group of 147 patients with recent onset RA. Disease activity and functional capacity were studied prospectively in this cohort. Activity of the disease was assessed once every three months by various parameters, and functional capacity was measured with a health assessment questionnaire once every six months. Ninety seven patients consented to participate in the study. Bone mineral density was assessed with dual energy x ray absorptiometry in the lumbar spine, in a combined region of interest in the hips, and in Ward's triangle. Multiple linear regression procedures were used to analyse the data. RESULTS: Duration of RA was negatively associated with BMD at all three sites of measurement. The mean erythrocyte sedimentation rate in the six months before BMD measurement was negatively associated with BMD in the hip and in Ward's triangle. Other parameters of disease activity were not related to BMD. The mean health assessment questionnaire score in the 18 months before BMD measurement was negatively associated with BMD in the combined hip region only. Bone mineral density tended to be decreased when patients were compared with a normal reference group, especially in the femoral regions of interest. CONCLUSIONS: It is concluded that BMD may be affected in patients with recent onset RA by disease dependent mechanisms. Several factors have been suggested elsewhere as determinants of BMD in RA. The results of this study show that disease duration, disease activity, and functional impairment may, independently of each other, contribute to bone loss, especially in the proximal femur.

Adult↗

Evaluation of indium-111-polyclonal immunoglobulin G to quantitate atherosclerosis in Watanabe heritable hyperlipidemic rabbits with scintigraphy: effect of age and treatment with antioxidants or ethinylestradiol.

Scintigraphic detection of atherosclerotic lesions using 111In-polyclonal IgG was studied. In Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for hypercholesterolemia with spontaneous atherosclerosis, aged WHHL rabbits incorporated more 111In-IgG into atherosclerotic lesions than young WHHL or control NZW rabbits. This result is in agreement with histological analysis. However, due to the low ratio of lesion-incorporated radioactivity to circulating radioactivity, in vivo gamma imaging of atherosclerosis with 111In-IgG scintigraphy was unsuccessful. Interventional agents, Probucol or vitamin E, used for 28 days to reduce the amount of autoantibodies produced against biological modified low-density lipoproteins did not produce differences in 111In-IgG incorporation into the aorta ex vivo. Ethinylestradiol, used for 28 days, exhibited similar incorporation with decreased serum cholesterol by 45%. Although atherosclerosis histology and lesion surfaces of WHHL rabbits are similar to those in adult humans, it is obvious that noninvasive gamma imaging with polyclonal 111In scintigraphy is not reliable for serial evaluation of the extent of atherosclerosis. Our results emphasize the need to develop pharmaceuticals to image atherosclerosis.

Age Factors↗

Indium-111-labeled polyclonal human immunoglobulin: identifying focal infection in patients positive for human immunodeficiency virus.

Pooled human immunoglobulin labeled with indium-111 (111In-HIgG) was used to identify the presence and extent of infection in patients positive for human immunodeficiency virus (HIV), presenting with either symptoms and/or signs of acute chest infection or with pyrexia without localizing signs or symptoms. Fifty-five studies were performed in 51 patients with suspected chest infection or pyrexia without localizing signs. Of these, 111In-HIgG identified intrapulmonary accumulation in 17 patients with Pneumocystis carinii pneumonia, eight with bacterial pneumonia, five with cytomegalovirus pneumonia, three with pulmonary Mycobacterium avium intracellulare infection and one with a fungal pneumonia. There was no intrapulmonary accumulation of 111In-HIgG in five patients with bronchopulmonary Kaposi's sarcoma and in three patients with intrathoracic lymphoma. Quantification of lung/heart activity was significantly increased (p < 0.05) in patients with active chest infection compared with those with intrapulmonary tumor or no active lung pathology. Indium-111-HIgG scintigraphy also localized at 14 sites of extrapulmonary infection, including six patients with colitis. There were no false-negative studies but false-positive uptake was seen in four studies. These results confirm that 111In-HIgG correctly identifies the presence and extent of infection in patients positive for HIV antibody.

AIDS-Related Opportunistic Infections↗

Intraoperative bone and bone marrow sampling: a simple method for accurate measurement of uptake of radiopharmaceuticals in bone and bone marrow.

Accurate estimation of bone marrow uptake of radiopharmaceuticals is of crucial importance for accurate whole body dosimetry. In this study, a method for obtaining normal bone marrow and bone during routine surgery without inconvenience to volunteers is suggested and compared to an indirect method. In five volunteers (group 1), 4 MBq 111In-labelled human polyclonal IgG (111In-IgG) was administered 48 h before placement of a total hip prosthesis. After resection of the femoral head and neck, bone marrow was aspirated from the medullary space with a biopsy needle. In five patients, suspected of having infectious disease (group 2), bone marrow uptake was calculated according to a well-accepted method using regions of interest over the lumbar spine, 48 h after injection of 75 MBq 111In-IgG. Bone marrow uptake in group 1 (4.5 +/- 1.3% D kg-1) was significantly lower than that in group 2 (8.5 +/- 2.1% D kg-1) (P < 0.01). Blood and plasma activity did not differ significantly for both groups. This method provides a system for directly and accurately measuring uptake and retention in normal bone marrow and bone of all radiopharmaceuticals at various time points. It is a safe and simple procedure without any discomfort to the patient. Since small amounts of activity are sufficient, the radiation dose to the patient is low.

Aged↗