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K J Kairemo

Publications and source records attributed to K J Kairemo.

At least 19 recordsLinked to original sources
PubMed2001

In vivo detection of intervertebral disk injury using a radiolabeled monoclonal antibody against keratan sulfate.

UNLABELLED: In the intervertebral disk, proteoglycans form the major part of the extracellular matrix, surrounding chondrocytelike disk cells. Keratan sulfate is a major constituent of proteoglycans. METHODS: We have radioiodinated a monoclonal antibody raised against keratan sulfate. This antibody was injected into rats (n = 6), and the biodistribution was studied. A model of intervertebral disk injury was developed, and two tail disks in each animal with both acute (2 wk old) and subacute (7 wk old) injuries were studied for in vivo antibody uptake. RESULTS: The biodistribution at 72 h was as follows: blood, 0.0018 percentage injected dose per gram of tissue (%ID/g); lung, 0.0106 %ID/g; esophagus, 0.0078 %ID/g; kidney, 0.0063 %ID/g; liver, 0.0047 %ID/g; spleen, 0.0046 %ID/g; heart, 0.0036 %ID/g; thyroid, 0.0034 %ID/g; muscle, 0.0017 %ID/g; and bone, 0.0016 %ID/g. In the subacute stage, a significant difference (P < 0.006) was found in antibody uptake between injured disks (n = 12) and adjacent healthy disks (n = 12). In vivo gamma imaging showed increased uptake in other animals having lumbar disk injuries (2, 7, and 17 d after injury). Cartilage tissue, such as the trachea, was studied separately and showed extremely high antibody uptake, 0.10 %ID/g. Rat trachea was also visualized on gamma images. CONCLUSION: Our data suggest that antibodies against nucleus pulposus components, such as proteoglycans, can be used for in vivo detection of intervertebral disk injury. This finding is in spite of the minimal circulation present in intervertebral disks.

Animals↗
PubMed2000

Subclinical cardiotoxicity following adjuvant dose-escalated FEC, high-dose chemotherapy, or CMF in breast cancer.

We compared adjuvant chemotherapy-related myocardial damage by antimyosin scintigraphy in patients who received either nine cycles of FEC (fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (group I, n = 14), three cycles of FEC followed by high-dose chemotherapy with alkylating agents (CTCb) given with the support of peripheral blood stem cell transplantation (group II, n = 14), or six cycles of standard intravenous CMF (cyclophosphamide, methotrexate and fluorouracil; group III, n = 8). The cardiac uptake of In-111-antimyosin-Fab (R11D10) antibody was measured and the heart-to-lung ratio (HLR) calculated 8-36 months after the last dose of chemotherapy. Cardiac antimyosin antibody uptake was considerably higher among patients treated with nine cycles of dose-escalated FEC than among those who were treated with three cycles of FEC and high-dose CTCb (HLR, median 1.98; range 1.36-2.24 vs median 1.51; range 1.20-1.82; P < 0.001), or those treated with CMF (median 1.44; range 1.15-1.68; P < 0.001). The difference between groups II and III was not significant (P > 0.1). A linear association was found between the cumulative dose of epirubicin and the cardiac antimyosin uptake (P < 0.001). We conclude that subclinical cardiac damage caused by three cycles of conventional-dose FEC followed by one cycle of high-dose CTCb chemotherapy is small as compared with the damage caused by dose-escalated FEC.

Adult↗
PubMed2000

Absorbed dose estimates for 131I-labelled monoclonal antibody therapy in patients with intraperitoneal pseudomyxoma.

Seven patients with intraperitoneal pseudomyxoma originating from the appendix (4 cases) and from the ovary (3 cases) were treated with radioimmunotherapy. During the therapy, nine infusions of 3.0-4.2 GBq of 131I-labelled B72.3 monoclonal antibody were administered. We developed three-dimensional dose calculation software that can utilize activity maps based on SPET images to calculate the absorbed dose distribution using point source kernels. The dose calculation program was employed to calculate absorbed doses to various organs. The calculated dose distributions enable us to evaluate the variation in dose within the organs, which is normally not available using approaches based on geometric models. The patient-specific absorbed dose calculations were compared with doses based on a model that uses photon S-factors derived from a standard phantom. The compared doses agreed well on average, but in some organs showed large discrepancies.

Antibodies, Monoclonal↗
PubMed2000

Endoglin is a suitable target for efficient imaging of solid tumors: in vivo evidence in a canine mammary carcinoma model.

Increasing evidence suggests that endoglin (CD105) is a new powerful marker of neovascularization in solid malignancies; thus, using breast cancer as a model, we investigated whether targeting of CD105 by monoclonal antibody (mAb) MAEND3 can be used for in vivo imaging of solid tumors. Immunohistochemistry and flow cytometry identified differential expression of CD105 on breast cancer and endothelial cells; in fact, neoplastic cells were weakly and rarely stained by mAb MAEND3, which in contrast, strongly and invariably stained blood vessel endothelia within the breast adenocarcinomas investigated and cultured endothelial cells. Moreover, in contrast to CD31, which currently represents the reference marker to assess angiogenetic activity, CD105 expression was highest in semiconfluent and actively proliferating endothelial cells, and it progressively decreased as cells reached tight confluency and low [3H]thymidine uptake. i.v. administration of 18 MBq of 125I-labeled mAb MAEND3 efficiently imaged spontaneous mammary adenocarcinomas in two dogs; the uptake of radiolabeled mAb was rapid and intense because tumor: background ratios of 8.2:1 and 9.3:1 were reached 8 h after mAb administration, in the absence of immediate and/or long-term clinical side effects. Altogether, our present data suggest that targeting of CD105 on tumor-associated blood vessels may represent a new strategy for in vivo imaging of solid malignancies, regardless of their histological origin.

Adenocarcinoma↗
PubMed1999

Imaging of McCune-Albright syndrome using bone single photon emission computed tomography.

UNLABELLED: McCune-Albright syndrome is a rare disorder caused by a somatic, constitutively activating mutation in the gene (GNAS1) encoding the subunit of the signal transducing guanine nucleotide binding protein (G protein). The condition is characterized by polyostotic fibrous dysplasia, cafe-au-lait pigmentation and multiple endocrine hyperfunction, most commonly gonadotropin-independent precocious puberty in girls. Our patient, a 16-year-old male, with radiologically confirmed polyostotic fibrous dysplasia in cranium, thoracic and pelvic girdles, spine and extremities was studied using planar 99mTc-hydroxymethyldiphosphonate bone scintigraphy and single photon emission computed tomography. Using bone scintigraphy, an unusually extensive and asymmetric fibrous dysplasia was observed in the cranium, face, ribs, femur, humerus, ulna, tibia and the vertebral column, all on the left side. The whole body scan revealed only a few foci on the right side. Single photon emission computed tomography demonstrated extensive unilateral involvement in the base of the skull, facial bones, maxilla and mandible. All the lesions reached only the midline. These findings formed the basis of further treatment, eg. reconstructive surgery of facial asymmetry. CONCLUSION: McCune-Albright syndrome should be considered in the differential diagnosis when interpreting extensive unilateral predominance in paediatric bone scans.

Adolescent↗
PubMed1999

A novel method for monitoring liver ethanol injections: activity tissue distribution in rat liver using digital quantitative autoradiography and CH3(14)CH2OH.

Accurate ethanol microdistribution during percutaneous ethanol injections (PEI) have not previously been reported by in vivo monitoring methods (e.g. by using ultrasound or other flow methods). Any real-time imaging method is insufficient to show the gradual diffusion of ethanol and its ultimate spread. Therefore a novel method to study the microdistribution and radiopharmacokinetics of labeled ethanol in rat liver was developed. Rats were injected with C-14-labeled ethanol into the right liver lobe. Liver slices were investigated at 1, 5, 15, and 30 min using a novel digital quantitative autoradiographic (DQAR) method. Tissue slices at 1 and 5 min demonstrated increased activity of C-14-labeled ethanol around the injection site, resulting in a uniform distribution at 15 min. At 30 min, a weak elimination was observed. Our results indicate that in PEI treatment, toxic effects may be found outside the primary injection site. Our DQAR method shows the dynamic spread of ethanol with great anatomical detail. It may therefore be used in future studies on ethanol kinetics in the liver and tumor tissues to optimize the antitumor effect of PEI while minimizing the potential for adverse spread and complications.

Administration, Cutaneous↗
PubMed1999

IgE myeloma: a case presentation and a review of the literature.

In the literature, fewer than 40 cases of IgE myeloma have been described. We report the first Norwegian case, an 80-year-old man presenting with progressive weakness, dyspnea and dizziness. With the exception of hypersedimentation, routine chemistry values were within reference limits. Plasma cells were not observed in the peripheral blood. Serum protein electrophoresis showed a monoclonal protein in the gammaglobulin fraction. Immunofixation confirmed the presence of an IgE kappa monoclonal protein. A bone marrow biopsy revealed an interstitial and nodular infiltration of abnormal plasma cells comprising 40% of nucleated cells present. Skeletal roentgenograms of this patient showed osteolytic lesions in the skull and in the left pubic arc. The findings for this patient were compared with the previous reports of IgE myeloma.

Aged↗
PubMed1999

131I radioconjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma--phase I and II study.

Locoregional radioimmunotherapy (LR-RIT) was administered to 111 patients (20 were recruited in a phase I and 91 in a phase II study) with malignant gliomas: 1 patient with oligodendroglioma, 7 patients with anaplastic oligodendroglioma, 2 with grade II astrocytoma, 10 with anaplastic astrocytoma and 91 with glioblastoma, amounting to 58 newly diagnosed and 53 recurrent tumours. The 131I-labelled monoclonal antibodies BC-2 and BC-4 were used in order to recognize stromal and intracellular glycoprotein tenascin, an antigen present particularly in glioblastoma. The patients were enrolled between February 1990 and December 1997 after conventional therapy. The radiopharmaceutical was injected directly into the tumour site. Sequential scintigraphies demonstrated a high and enduring uptake in the tumour. The mean irradiation dose in the tumour was 300 Gy per cycle. In the group of 74 phase II glioblastoma patients the clinical responses were as follows: 10 patients with stable disease (SD), 9 with partial responses (PR), 23 with no evidence of disease (NED) and 1 patient with complete response (CR). The median survival was 19 months. The response rate (CR + PR + NED) was 17.8% for those patients with bulky lesions, with a median survival of 17 months, but 66.6% for patients with small lesions, with a median survival of 25 months. Better outcomes were recorded in cases with less aggressive diseases: oligodendroglioma, anaplastic oligodendroglioma and anaplastic astrocytoma. We conclude that fractionated LR-RIT can be safely performed, with promising results especially in patients with minimal disease.

Adult↗
PubMed1999

The use of TL detectors in dosimetry of systemic radiation therapy.

A method for determining absorbed doses to organs in systemic radiation therapy (SRT) is evaluated. The method, based on thermoluminescent (TL) dosimeters placed on the patient's skin, was validated and justified through a phantom study showing that the difference between measured (TL dosimeters in the phantom) and derived (TL method) values is within 10%. Six radioimmunotherapy (RIT) patients with widespread intraperitoneal pseudomyxoma were also studied. In dose evaluations, special emphasis was on kidneys. In addition to the TL method, the absorbed doses to kidneys were calculated using MIRD formalism and a point dose kernel technique. We conclude that in SRT the described TL method can be used to estimate the absorbed doses to those critical organs near the body surface within 50% (1 SD).

Adult↗
PubMed1999

The role of pulmonary and systemic circulation in the tracheal blood supply in rats.

The different roles of bronchial and pulmonary circulation in the tracheal blood supply were investigated in 26 female rats: a control group (CG, n = 7), a group with pulmonary hilar ligation (PL, n = 5), another with tracheal transsection (TL, n = 9) and a group with both these procedures (TL&PL, n = 5). Technetium 99-m was injected into the left ventricle postoperatively, and the radioactivity of tracheal samples was calculated as a percentage of injected activity/g tissue (%ID/g). The tracheal uptake averaged 1.9 in group CG, and 1.7, 1.3 and 1.5% ID/g in groups PL, TL and TL&PL, respectively. Tracheal transsection (TL) thus reduced the tracheal blood supply by 29.7% compared with the control group (p < 0.05), whereas the reduction of tracheal blood supply following pulmonary hilar ligation (PL) was only 10.9% (n.s.). Tracheal transsection combined with hilar ligation (TL&PL) effected a reduction of 19.9% (n.s.). We conclude that only 10.9% of the tracheal blood supply comes from the pulmonary circulation.

Animals↗
PubMed1999

Monoclonal gammopathy may disturb oestradiol measurement in the treatment and monitoring of in-vitro fertilization: case report.

A 31 year old woman had her treatment for infertility by in-vitro fertilization (IVF) cancelled because a highly elevated serum concentration of oestradiol was detected, contrary to the clinical picture and that observed by vaginal ultrasound. The immunoassay for measuring oestradiol had been affected by circulating heterophilic antibodies in the form of an elevated immunoglobulin (Ig) G-kappa M component. This may often be associated with a haematological malignancy of lymphoid origin, but this patient had a benign monoclonal gammopathy. Monoclonal gammopathy has not been described in IVF patients previously, nor has monoclonal gammopathy been reported as a cause of erroneously elevated oestradiol concentration. This sort of interference in oestradiol analysis is probably very rare, but may lead to unnecessary cancellation of the treatment. A highly elevated oestradiol that is not in accordance with the clinical course may indicate heterophilic antibody interference, and the cause should always be investigated.

Adult↗
PubMed1998

Expression profile of vascular cell adhesion molecule-1 (CD106) in the middle ear using radiolabeled monoclonal antibody.

Adhesive interactions between leukocytes and endothelium are required for subsequent leukocyte extravasation toward inflammatory sites. Understanding the possible kinetic expression of vascular cell adhesion molecule-1 (VCAM-1) in the middle ear cavity during an inflammatory cascade in vivo may be important for clarifying local immunological responses in otitis media. Two inflammatory models were produced in the rat and involved acute middle ear mucosal and cutaneous inflammation induced after inoculation or intradermal injection of lipopolysaccharide (LPS). After intravenous injection of both 125I-labeled anti-VCAM-1 and 131I-labeled control monoclonal antibody (mAb), the kinetic expression of VCAM-1 in the middle ear and skin was assessed by local radionuclide uptake. The biodistribution of an 125I-labeled anti-VCAM-1 mAb as a potential detector of focal inflammation was examined in normal rats. Both inflammatory lesions were characterized by early and sustained (up to 24 h) expression of VCAM-1, with maximal expression at 4 h after LPS stimulation. The kinetics of VCAM-1 expression was similar among the middle ear mucosa or skin specimens studied and different stimulation methods. A similar biodistribution and clearance of radioactivity between 125I-labeled anti-VCAM-1 mAb and 131I- or 99mTc-labeled control mAb were observed. The present result suggest that functional VCAM-1 induced by LPS is expressed in both middle ear tissue and skin lesions and may play a role in the initial stage of inflammatory response produced. Although VCAM-1 upregulation is a very early event in the inflammatory cascade, 125I-labeled anti-VCAM-1 mAb may be useful for the early detection of focal inflammation in the middle ear.

Animals↗
PubMed1998

Imaging of olfactory neuroblastoma--an analysis of 17 cases.

A total of 17 histologically confirmed olfactory neuroblastomas treated at Helsinki University Central Hospital between 1962 and 1996 were reviewed retrospectively. The tumors displayed a variety of imaging characteristics and aggressiveness. Imaging evolved from plain X-rays at the beginning of the study period to CT and MRI during the latter part of the study. CT provided the best information about the tumor and its local invasion especially into surrounding bony structures. MRI allowed an estimate of tumor spread into surrounding soft-tissue areas, such as the anterior cranial fossa and the retromaxillary space. However, signal intensity characteristics were not specific for olfactory neuroblastomas. Bone scintigraphy and MIBG scan allowed us to detect distant metastases. Olfactory neuroblastoma is an aggressive malignancy and the prognosis is poor in most cases, as shown by the short survival rates (average 45.3 months) in our study group. The tumor can be detected, delineated and its characteristics suspected by modern radiology. Definite diagnosis is based on histopathology. This study proposes general imaging strategies for detecting this disease.

Adolescent↗
PubMed1998

Labelling of bleomycin with Auger-emitter increases cytotoxicity in squamous-cell cancer cell lines.

PURPOSE: To investigate the cytotoxicity of bleomycin (BLM), two Auger-emitting bleomycin complexes (indium-111 ((111)In)-BLMC) and (111)InCl3 in three squamous cell cancer (SCC) cell lines. MATERIAL AND METHODS: Three recently established SCC cell lines were investigated using the 96-well clonogenic assay. Concentrations causing 50% inhibition in cell survival (IC50) were calculated for BLM and two specific activities of (111)In-BLMC (40 MBq/mg BLM (low) and 195 MBq/mg BLM (high)). RESULTS: (111)In-BLMC (low) was the most toxic to the SCC cell lines. (111)In-BLMC containing 4.9-fold more activity of (111)In (195 MBq/mg BLM) was more effective than BLM (p=0.0029), but not as toxic as (111)In-BLMC (low) (p=0.0023). UT-SCC-19A had a IC50 value for BLM as low as 4.1 nM, whereas IC50 values for (111)In-BLMC (low) and (111)In-BLMC (high) were 2.0 nM and 2.6 nM, respectively. The most chemoresistant cell line UT-SCC-12A had a IC50 value for BLM of 18.8 nM, for (111)In-BLMC (low) 10.7 nM and for (111)In-BLMC (high) 12.7 nM. (111)InCl3 had no cell killing effect. CONCLUSIONS: This study shows that (111)In-BLMC is superior in SCC cell killing compared with BLM. These data provide the basis for further clinical investigations of (111)In-BLMC.

Antimetabolites, Antineoplastic↗
PubMed1998

A dual-tracer method for studying intragastric distribution and gastric emptying of solids and liquids in functional dyspepsia.

Twenty-five patients with functional dyspepsia and 11 healthy controls matched for age and sex were examined. The patients were divided into two groups: patients with dysmotility-like symptoms and those with ulcer-like symptoms. In a dual-tracer gastric emptying study, dysmotility-like and ulcer-like symptoms could not be distinguished from each other on the basis of gastric emptying times. The intragastric distribution and the solid lag time in dysmotility-like dyspepsia differed significantly from those of the controls.

Adult↗