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Biomedical subjects

R A Claessens

Publications and source records attributed to R A Claessens.

47 records · Page 3Linked to original sources
PubMed1991

Kinetics and biodistribution in relation to tumour detection with 111In-labelled OV-TL 3 F(ab')2 in patients with ovarian cancer.

The biological behaviour of 111In-labelled OV-TL 3 F(ab')2 was studied in 22 patients with suspected ovarian cancer. After i.v. injection with 140 MBq 111In-OV-TL 3 F(ab')2 (1 mg) blood samples were taken up to 96 h and urine and faeces were collected throughout the whole study. At surgery, 5 to 7 days post-injection, primary and metastatic tumour tissues, as well as fragments of several normal tissues, were removed and 111In uptake was measured. Blood activity disappeared with half-life values of 6.1 +/- 1.1 and 17.9 +/- 6.5 h. Within 96 h excretion in urine and faeces was 16.1 +/- 2.0% i.d. (mean +/- S.D.) and 3.1 +/- 1.9% i.d., respectively. Mean tissue uptake, expressed as % i.d. kg-1 was 3.9 +/- 1.0 for primary tumour, 11.5 +/- 5.0 for liver and 0.4 +/- 0.1 for several normal background tissues. Higher tumour uptake correlated with a higher detection rate at immunoscintigraphy. However, no strict correlation was found between the amount of tumour uptake and the expression of the monoclonal antibody defined OA3 antigen. Quantitation of organ activity, using region of interest analysis, resulted in mean peak organ activities for the liver of 16% i.d., spleen 9% i.d. and kidney 4% i.d. Distribution data indicate that besides specific antibody-antigen interaction several other mechanisms play a role in uptake in tumour and other tissues.

Animals↗
PubMed1991

Detection of subacute infectious foci with indium-111-labeled autologous leukocytes and indium-111-labeled human nonspecific immunoglobulin G: a prospective comparative study.

In 35 patients suspected of an infectious focus, the outcome of scintigraphy with 111In-labeled autologous leukocytes (WBC) and 111In-labeled human nonspecific immunoglobulin G (IgG) was evaluated in a prospective comparative study. Clinical, roentgenologic and microbiologic findings were considered to be proof of the presence of infection or inflammation. In this group of patients with mainly subacute infections, 111In-IgG scintigraphy performed significantly better than 111In-WBC scintigraphy, especially in infections of the locomotor system, but also in various soft-tissue infections. Both techniques showed disappointing results in patients with disseminated yersinia infection and in some patients with tuberculosis. Overall sensitivity and specificity was 74% and 100% for 111In-IgG scintigraphy and 52% and 78% for 111In-WBC scintigraphy, respectively.

Bacterial Infections↗
PubMed1990

Immunoscintigraphy of ovarian cancer with indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody.

The safety and diagnostic accuracy of immunoscintigraphy with the indium-111-labeled monoclonal antibody OV-TL 3 F(ab')2(111In-OV-TL 3 F(ab')2) for diagnosis and follow-up of ovarian cancer was prospectively studied in 31 patients. Planar and SPECT scintigraphy were performed up to 4 days after i.v. injection of 140 MBq 111In-OV-TL 3 F(ab')2. Surgical evaluation was possible in 22 out of 31 patients. Imaging results were compared with X-ray computed tomography, ultrasound, and CA 125 serum level using the histologically confirmed surgical findings as a "gold standard." Apart from a transient rash observed in two patients, no other immediate or delayed adverse reactions were observed. Within the surgically evaluated group, ovarian cancer lesions were detected in 16 out of 17 patients (94%). Of 45 distinct tumor deposits found at operation, 67% were detected and localized with immunoscintigraphy while X-ray computed tomography and ultrasound visualized 53% and 23%, respectively.

Adult↗
PubMed1990

Scintigraphic detection of bone and joint infections with indium-111-labeled nonspecific polyclonal human immunoglobulin G.

The utility of indium-111-(111In) labeled immunoglobulin G (IgG) to detect infection of bone and adjacent tissues was investigated. Proof of infection was obtained by cultures taken at surgery. All 32 patients showed focally increased uptake on the technetium-99m- (99mTc) methylene diphosphonate (MDP) skeletal scintigraphies. Labeled immunoglobulin correctly identified presence, location, extent and soft-tissue involvement of the suspected inflammatory site. In these patients, focally increasing accumulation was noted over 48 hr. Discrimination between infection and sterile inflammatory lesions was not possible. Two fractures, 6-mo-old, and an aseptic loosening of a total-hip prosthesis were not visualized. Side effects after the immunoglobulin administration were not observed. Radiolabeled immunoglobulin is a new and safe radiopharmaceutical for the investigation of infectious bone and joint disease. The sensitivity of this agent appears at least as high as that of labeled leukocytes. However, labeled immunoglobulin can easily be prepared in every nuclear medicine department.

Arthritis, Infectious↗
PubMed1981

Adrenal scintigraphy in primary aldosteronism. Improved visualization after long-term pre-treatment with dexamethasone.

Dexamethasone-modified adrenal scintigrams were performed on 13 patients with an aldosterone-producing adenoma and on one patient with an aldosterone-producing carcinoma. Adrenal scintigrams using 131I-19-Iodocholesterol were obtained after short pre-treatment with dexamethasone, while 131I-6 beta-Iodomethyl-19-Nor-Cholesterol scintigrams were performed after long-term pre-treatment with dexamethasone during 9-21 days. Using the former procedure the adrenal scintigrams correctly identified the adenoma in 3 of 8 patients, while with the latter procedure the adrenal scintigrams localized the adenomas in 8 out of 9 patients, including 3 patients in whom the former procedure had failed. The adrenal carcinoma was not visualized with 131I-6 beta-Iodomethyl-19-Nor-Cholesterol. Thus, the sensitivity of 131I-19-Iodocholesterol scintigrams to detect aldosterone-producing adenomas was only 37.5%. Uptake of radioactivity in the normal contralateral adrenal gland accounted for the low detection rate. On the other hand, the 131I-6 beta-Iodomethyl-19-Nor-Cholesterol scintigrams, performed after long-term pre-treatment with dexamethasone, had a sensitivity of 89%. It is suggested that long-term pre-treatment with dexamethasone contributed to the improved sensitivity by a more effective suppression of radioactivity uptake in the normal adrenal gland.

19-Iodocholesterol↗
PubMed1975

Coronary blood flow in rats native to simulated high altitude and in rats exposed to it later in life.

In rats exposed to a simulated high altitude of 3500 m for their whole prenatal and postnatal life a severe cardiac hypertrophy develops. In rats born and first staying 5 weeks at sea level and then being exposed to simulated high altitude, only a unilateral right cardiac hypertrophy occurs. In both groups nutritional coronary blood flow was estimated in left ventricle, right ventricle, and septum and was compared with control animals of similar age. Coronary blood flow was measured at hypoxia in all groups. At first cardiac output was determined by the Fick principle, then 86Rb was applied and the animals were killed after 55 sec. Activity of 86Rb was measured in both cardiac ventricles and septum and the fractional uptake was calculated. According to Sapirstein (1956, 1958) the distribution of 86-RB follows the distribution of cardiac output and from both these data the nutritional blood flow to the parts of the heart may be estimated. Cardiac output was similar in rats exposed to simulated high altitude later in life ('newcomers') and in control animals, but it was significantly lower in rats born in the low pressure chamber ('natives'). Fractions of cardiac output supplying cardiac ventricles and septum in rats from both hypoxic groups were significantly higher than in control animals. In the 'natives' they were significantly higher than in the 'newcomers'. The fractions of cardiac output in both 'newcomers' and 'natives' remained significantly higher than those of the control animals, also when calculated per gram of heart tissue. Nutritional coronary blood flow (in ml/min) was higher in both ventricles and septum of the 'newcomers' and in the right ventricle of the 'natives', and lower in the septum of the 'natives', when compared with control animals. Coronary blood flow per gram of heart tissue (in ml/min.g) was significantly higher in all cardiac parts of the 'newcomers', but it was about the same in all cardiac parts of the 'natives' when compared with controls. The importance of observed changes concerning myocardial tissue oxygenation is analyzed by using Krogh's cylindrical tissue model.

Age Factors↗
PubMedDate not supplied

Biodistribution of iodine-125 and indium-111 labeled OV-TL 3 intact antibodies and F(ab')2 fragments in tumor-bearing athymic mice.

The monoclonal antibody OV-TL 3, directed against an ovarian carcinoma-associated antigenic determinant, was tested as a vehicle for radioimmunolocalization of ovarian carcinomas in athymic mice bearing NIH:OVCAR-3 xenografts. The biodistribution of intact. OV-TL 3 was compared with the distribution of OC 125. Tumor uptake with OV-TL 3 was significantly higher than with OC 125, and almost 7 times higher than with a non-specific control antibody (OV-TL 19). Administration of a mixture of intact OV-TL 3 and OC 125 did not improve tumor uptake in comparison with OV-TL 3 alone. Subsequently, intact OV-TL 3 and its F(ab')2 fragments were labeled with either 111In or 125I. The highest tumor uptake was obtained with 111In-labeled intact OV-TL 3 (14.7% ID/g, 48 hr p.i.). For both antibody forms uptake of 111In in liver, spleen and kidneys was very high. Furthermore, 111In cleared more slowly from most tissues than 125I. As a result, tumor/tissue ratios with 111In-labeled OV-TL 3 were lower than with 125I-labeled OV-TL 3. The highest tumor/tissue ratios (6.9 to 53) were obtained with 125I-labeled OV-TL 3 F(ab')2 fragments, 48 hr post injection. 111In-labeled OV-TL 3 F(ab')2 has already been shown to be a clinically useful label for the detection of ovarian cancer. The results of our comparative animal study suggest that these clinical results may even be improved by using 123I-labeled OV-TL 3 F(ab')2.

Animals↗
PubMedDate not supplied

Tumour targeting of the anti-ovarian carcinoma x anti-CD3/TCR bispesific monoclonal antibody OC/TR and its parental MOv18 antibody in experimental ovarian cancer.

The anti-tumour x anti-T-cell bispecific monoclonal antibody (biMAb) OC/TR is a biologically produced biMAb combining the anti-ovarian carcinoma activity of the MOv18 MAb with anti-CD3/T-cell receptor (TCR) complex activity. In this study, the in vitro binding characteristics of the OC/TR biMAb and its tumour targeting potential in nude mice with Hela tumours was studied. Scatchard analysis revealed that the affinity constant of the biMAb was 7 times lower than the affinity of the parental MOv18 antibody. Uptake of the OC/TR antibody in the Hela xenografts in nude mice was significantly higher than the tumour uptake of an irrelevant control antibody, indicating that the radioiodinated OC/TR biMAb specifically localized in the tumour xenografts. However, tumour uptake was significantly lower than the tumour uptake of the parental MOv18 antibody. This reduced tumour uptake most likely is a result of its reduced affinity. We conclude that, despite the loss of bivalent tumour cell binding, the biMAb OC/TR can still specifically localize in tumours. This indicates that the first prerequisite of an effective therapeutic approach using systemically applied biMAb can be met. Whether the interaction with human T-cells will affect the tumour targeting potential of the biMAb in patients remains to be investigated.

Animals↗