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Biomedical subjects

R A Claessens

Publications and source records attributed to R A Claessens.

At least 37 records · Page 2Linked to original sources

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↗

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↗

Indium-111-labeled human nonspecific immunoglobulin G: a new radiopharmaceutical for imaging infectious and inflammatory foci.

Indium-111-labeled human nonspecific immunoglobulin G (111In-IgG) is a newly developed radiopharmaceutical for imaging infectious and inflammatory foci. This article presents an overview of the literature concerning 111In-IgG scintigraphy. The current theory about the mechanism of accumulation suggests that 111In-IgG accumulates in lesions as a result of enhanced vascular permeability and subsequent entrapment of the radiolabeled protein. Human studies show excellent results in imaging bone and joint, abdominal, and intravascular infection. Of special interest is the ability to depict infectious foci in granulocytopenic patients. The value of 111In-IgG scintigraphy for detection of infection is compared with that of gallium-67, labeled-leukocyte, and technetium-99m (99mTc) nanocolloid scintigraphy. The significance of differences between 111In-IgG scintigraphy and two other new scintigraphic techniques, 99mTc-labeled IgG and 99mTc-labeled murine monoclonal anti-granulocyte antibody BW 250/183, are discussed.

Animals↗

Tumour detection and localization using 99Tcm-labelled OV-TL 3 Fab' in patients suspected of ovarian cancer.

Fab' fragments of the monoclonal antibody OV-TL 3, that recognizes an ovarian carcinoma-associated antigen (OA3), were labelled with 99Tcm using D-glucarate as a ligand. Twenty patients suspected of having primary or recurrent ovarian cancer received intravenously 1 mg of the Fab' labelled with 740 MBq 99Tcm. Both planar and single photon emission computed tomographic (SPECT) scintigraphy were performed up to 30 h after intravenous infusion. In 19 out of 20 patients surgical and histopathological evaluation was performed between 2 and 6 days postinfusion. Imaging results were compared with X-ray computed tomography (CT), ultrasonography (US) and CA 125 serum level. Blood clearance was fast with median t1/2 beta of 9.5 h. Thirty-seven per cent of the injected dose (% ID) was excreted in the urine within the first 24 h, whereas 7% ID was excreted in the 24 h faeces. In one patient with an OA3 negative ovarian carcinoma, radioimmunoscintigraphy (RIS) did not visualize the tumour. In two other patients a benign ovarian cyst was found, also showing no elevated uptake. In 13 out of 17 patients ovarian cancer lesions were detected with RIS, whereas CT and US detected lesions in, respectively, 15 and 12 patients. Of 36 surgically defined tumour deposits larger than 1 cm in diameter, 53% were detected and localized with RIS, whereas CT and US detected 61 and 40%, respectively. Radioimmunoscintigraphy with 99Tcm-OV-TL 3 Fab' is less distressing for the patients but the overall imaging performance is not improved when compared with 111In-OV-TL 3 F(ab')2.

Adult↗

Diagnosis of bone, joint, and joint prosthesis infections with In-111-labeled nonspecific human immunoglobulin G scintigraphy.

The diagnostic accuracy of scintigraphy performed after injection of indium-111-labeled nonspecific human immunoglobulin G (IgG) was studied in 113 patients with 120 foci of suspected infection in bone (52 chronic and eight acute infections), joints (15 localizations), joint prostheses (37 prostheses), and soft tissue of the locomotor system (eight localizations). All patients also underwent standard three-phase scintigraphy after injection of technetium-99m-labeled methylene diphosphonate. A scan obtained with In-111-labeled IgG was considered positive if focal increasing accumulation was noted over time. In 51 patients (45.1%), the results of scintigraphy were verified with intraoperative cultures, and in 21 patients (18.6%), with needle aspiration. The prevalence of infection was 59%; overall sensitivity, 97%; and specificity, 85%. Use of In-111-labeled IgG enabled correct identification of the presence, site, and extent of infection in 69 of 71 proved foci of infection; 41 of 48 negative studies were correct. Only two infections proved with culture were missed; in both patients, the cultures revealed growth of Staphylococcus aureus in low counts.

Arthritis, Infectious↗

Diagnosing infection in febrile granulocytopenic patients with indium-111-labeled human immunoglobulin G.

PURPOSE: Delineation of focal infection is a major problem in the management of febrile granulocytopenic patients. The utility of indium-111-labeled human nonspecific immunoglobulin G (In-111-IgG), a newly developed radiopharmaceutical for imaging focal inflammation, was reported in patients with adequate WBC counts. In the present study, we investigated whether In-111-IgG scintigraphy could be used to locate infection in granulocytopenic patients. MATERIALS AND METHODS: Granulocytopenic rats with focal infection were imaged after In-111-IgG injection. Thereafter, In-111-IgG scintigraphy was performed in 20 granulocytopenic patients. Images were obtained 4, 24, and 48 hours after injection of 75 mBq In-111-IgG. Scintigraphic findings were compared with clinical, roentgenologic, and ultrasonographic methods and culture results. RESULTS: In the animal model high In-111-IgG accumulation was observed in the infectious focus. In the patients, 13 proven pulmonary, abdominal, joint, and soft tissue infections of both bacterial and fungal origin were detected adequately. In-111-IgG uptake not due to verified inflammation was observed in the large bowel of two patients. A thoracic wall infiltrate showing only mild inflammatory activity was not detected. Small toxoplasmosis lesions in heart, liver, and kidneys were obscured by physiologic In-111-IgG activity in these organs. CONCLUSIONS: In-111-IgG scintigraphy is a useful technique to delineate focal infection in patients with granulocytopenia. Accumulation of the radiopharmaceutical does not appear to be granulocyte-mediated. In-111-IgG is a safe and convenient radiopharmaceutical that probably contributes to the early diagnosis of focal infection in granulocytopenic patients.

Adolescent↗

Dosimetric evaluation of immunoscintigraphy using indium-111-labeled monoclonal antibody fragments in patients with ovarian cancer.

This study reports the biodistribution and dosimetry for a monoclonal antibody against ovarian carcinoma. Eight patients received 140 MBq 111In-OV-TL 3 F(ab')2; thereafter gamma camera imaging was performed daily up to 96 hr. By using the conjugated view counting method, activity in the organs was quantitated by phantom calibration and by whole-body measurements using a whole-body counter with the conjugated view counting method. Red bone marrow uptake was derived from regions of interest over the lumbar vertebrae and iliac crest. In both methods, organ uptake varied only slightly with time, having a mean value of approximately 18%, 4%, 6% and 17% of the injected dose in the liver, spleen, kidneys and red bone marrow, respectively. The mean radiation dose to these organs was 0.9, 1.5, 1.2 and 0.5 mGy/MBq. The effective dose equivalent was 0.4 mSv/MBq. In this study, two different methods of uptake calculations, result in similar values of organ uptake.

Aged↗

Evaluation of infectious diabetic foot complications with indium-111-labeled human nonspecific immunoglobulin G.

Osteomyelitis of the foot is a well-known complication of diabetes mellitus. In this study, the validity of 111In-labeled human nonspecific immunoglobulin G (IgG) scintigraphy was studied in 16 diabetic patients with foot ulcers, gangrene or painful Charcot joints. In all patients, plain radiographs, conventional bone scan images and 111In-IgG images were recorded. The results were verified by histologic examination of surgical specimens in patients who did not respond to antibiotic treatment within 2-3 wk (10 lesions) or long-term clinical follow-up of at least 6-mo (16 lesions). On the bone scans, all seven osteomyelitic foci were detected. However, 19 additional foci not due to osteomyelitis were seen. The absence of true-negative bone scans in this study resulted in a specificity of 0%. On the plain radiographs, four of seven osteomyelitis foci were detected; for 111In-IgG scintigraphy, six of seven (sensitivity 57% and 86%, respectively). Plain radiographs correctly ruled out osteomyelitis in 15 of 19 lesions, 111In-IgG scintigraphy in 16 of 19 (specificity 79% and 84%, respectively). All imaging procedures gave false-positive results in penetrating ulcers over the calcaneus in two patients and in one patient with a Charcot joint, most likely due to recent fractures. A false-negative 111In-IgG study was observed in a patient with severe arterial angiopathy. Accurate estimation of probable osteomyelitis was not possible from the results of soft-tissue cultures, since in only 6 of 12 positive cultures, osteomyelitic foci could be proven. Indium-111-IgG scintigraphy can contribute to adequate evaluation of osteomyelitis in diabetic foot complications because it improves specificity when compared to bone scan and radiographic findings and improves sensitivity in comparison to plain radiographs.

Adult↗

Biodistribution and kinetics of radiolabeled proteins in rats with focal infection.

The purpose of this study was to evaluate the role of both protein and radionuclide in the accumulation of 111In-labeled human immunoglobulin G (IgG) in infectious foci. In rats with a calf muscle infection, biodistribution was determined 2, 6, 24, and 48 hr after injection of a radiopharmaceutical. For IgG, human serum albumin (HSA) and human immunoglobulin A (IgA), all labeled with 111In, target-to-background (T/B) ratios were similar throughout the study. However, absolute abscess uptake of 111In-IgA was significantly lower. For IgG labeled with 111In, 123I, or 99mTc, similar T/B ratios were found up to 24 hr. After 48 hr, the T/B ratio of 111In-IgG was significantly higher than the T/B ratio of 123I-IgG. The absolute abscess uptake of 111In-IgG was higher than that of 99mTc-IgG at 24 hr and 123I-IgG at 48 hr. In conclusion, the radionuclide appears to be of major importance in the accumulation of radiolabeled proteins in infectious foci. Protein mainly influences blood clearance and distribution in organs. The Fc-gamma receptor is not crucial for accumulation in infectious foci.

Abscess↗