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R Senekowitsch-Schmidtke

Publications and source records attributed to R Senekowitsch-Schmidtke.

30 records · Page 2Linked to original sources
PubMed1998

Tumor cell spheroids as a model for evaluation of metabolic changes after irradiation.

UNLABELLED: Tumor cell spheroids provide a good model to evaluate the relationship between tumor volume and the number of viable cells in the volume with the uptake of metabolic tracers before and after therapy. They represent the only in vitro model that allows the determination of the activity per unit volume, a parameter which is relevant for interpretation of PET studies. The purpose of this study was to evaluate this model with respect to the uptake of 14C-FDG, 3H-methionine and 3H-thymidine with and without exposure to irradiation. METHODS: Spheroids of the human adenocarcinoma cell line SW 707 were incubated in media containing 14C-FDG, 3H-methionine or 3H-thymidine for 1 hr at 1, 4, 8, 24 and 48 hr after exposure to a single radiation dose of 6 Gy together with control spheroids. Tracer uptake after incubation was expressed in cpm/ spheroid, cpm/1000 viable cells and cpm/0.01 mm3. In addition, the proliferative capacity of control and irradiated spheroids was determined using the clonogenic assay. RESULTS: Spheroid uptake of FDG decreased with time after irradiation, while the uptake per 1000 viable cells was increased significantly. The activity per unit volume remained unchanged in comparison to control spheroids. Methionine uptake per spheroid was unchanged after irradiation because of the high increase in uptake per 1000 viable cells. Uptake per unit volume also remained unchanged in comparison to controls. Thymidine uptake per 1000 viable cells did not change after irradiation but showed significant differences in uptake per spheroid and per unit volume compared to controls. The percentage of thymidine incorporated into the TCA-precipitable fraction containing DNA was 50% in controls and decreased to 12% at 24 hr after irradiation. The suppressed clonogenic capacity early after therapy recovered with the increase in thymidine uptake and with the increase in thymidine incorporation into DNA. CONCLUSION: The results show that the activity determined within a certain tumor volume is a balance between the increased tracer uptake by surviving cells after therapy and the lack of tracer uptake by dead cells, which still contribute to the tumor volume. Thus, the resulting unchanged activity per unit volume within the spheroid, as found for FDG and methionine, may not fully reflect therapy-induced metabolic changes in tumors.

Adenocarcinoma↗
PubMed1997

[Occurrence of immune hyperthyroidism after radioiodine therapy of autonomous goiter].

AIM: The goal of the study was to examine the prevalence of Graves' disease following I-131 treatment of autonomous goiter with special regard to pretreatment scintigraphic patterns. PATIENTS AND METHOD: Pre- and posttreatment in-vitro and in-vivo parameters were studied in 375 consecutive patients treated with I-131 therapy for nodular or diffuse autonomous goiter. All patients included were within ambulant control for at least 2.5 months following treatment. According to the pretreatment Tc-99m pertechnetate scan 59% (220/375) had multifocal (MF), 23% (86/375) unifocal (UF), 10% (38/375) mixed focal-disseminated (FD) and 8% (31/375) disseminated (D) scintigraphic patterns. RESULTS: In 93.9% (352/375), the autonomous tissue was totally, in 2.1% (8/375) partially and in 1.6% (6/375) insufficiently eliminated. In 2.4% (9/375) a relapse of hyperthyroidism was observed 2 to 10 months following I-131 therapy. In 8 patients a relapse of hyperthyroidism was accompanied or followed by an elevation of the previously non-elevated TSH-receptor antibody (TRAb) level and in 1 patient by an TRAb increase to the upper borderline range implicating Graves' disease. With the prevalence of Graves' disease following I-131 therapy a statistically significant difference in pretreatment Tc-99m pertechnetate scintigraphic patterns was found: 0% of unifocal (0/86) or multifocal (0/220), however 18% (7/38) of focal-disseminated and 7% (2/31) of disseminated scintigraphic patterns. From the 366 patients without relapse of hyperthyroidism 2 (MF) had elevated pre- and posttreatment TRAb levels and 3 (D) had elevated TRAb levels for the first time after I-131 therapy. CONCLUSION: There is a low overall prevalence (2.4%) of Graves' disease following I-131 therapy for nodular or diffuse autonomous goiter. However, the prevalence of posttreatment Graves' disease is highly dependent upon pretreatment scintigraphic patterns exhibiting focal-disseminated or disseminated patterns.

Adult↗
PubMed1997

Oxygen tensions in rodent tumors after irradiation with neutrons.

We started investigations on intratumoral oxygen tension after irradiations with reactor fission neutrons using the Eppendorf-pO2 Histograph. Isotransplanted AT17-mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on balb C-mice received 2 or 6 Gy neutrons single dose. Before and at certain points of time after treatment the pO2 values were evaluated. Some tumors with initially low median pO2 values showed a short-lasting increase between 2 and 24 h after irradiation. In those tumors with relatively high pretherapeutic pO2 values the pO2 decreased to the range of hypoxia. A third group of tumors showed no marked changes after irradiation. No tumor stopped growth during the observation period.

Animals↗
PubMed1996

Therapeutic effect of m-[131I]- and m-[125I]iodobenzylguanidine on neuroblastoma multicellular tumor spheroids of different sizes.

m-[l25I]iodobenzylguanidine (m-[125I]MIBG) has been suggested as an alternative to m-[131I]MIBG for the treatment of metastatic neuroblastoma to achieve a higher radiation dose in micrometastases. To compare these two radiopharmaceuticals, a mathematical model was developed in the present study that allows for the calculation of radiation dose rates within small spherical tumors for different distributions of 131I and 125I. Furthermore, the relationship between tumor size and the therapeutic effects of m-[131I]- and m-[125I]MIBG was studied in vitro using multicellular tumor spheroids of the neuroblastoma cell line SK-N-SH. According to the calculations, higher mean dose rates can be achieved by m-[125I]MIBG than by m-[131I]MIBG up to a tumor diameter of 100 microm when both substances are homogeneously distributed within the tumor. In larger tumors, however, mean dose rates achieved by 131I are up to 8-fold higher. Evaluation of various activity distributions demonstrated that even in tumors of less than 100 microm in diameter, marked heterogeneities of the dose rate can occur when m-[125I]MIBG is not distributed homogeneously. By treatment with m-[131I]MIBG, the growth of tumor spheroids ranging from 100 to 250 microm in diameter was inhibited more effectively in the larger than in the smaller spheroids. The growth inhibition of spheroids treated with m-[125I]MIBG was independent of the spheroid size. In consistency with the calculations, the therapeutic effect of m-[125I]- and m-[131I]MIBG was equal in spheroids with diameters of about 100 microm. In larger spheroids, m-[131I]MIBG induced a more pronounced delay in spheroid growth than m-[125I]MIBG. According to these calculations and in vitro data, m-[125I]MIBG as a single agent does not seem to be a promising alternative to m-[131I]MIBG for treatment of metastatic neuroblastoma. However, the combined use of m-[131I]- and m-[125I]MIBG may be more effective than treatment with m-[131I]MIBG alone.

3-Iodobenzylguanidine↗
PubMed1996

Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography.

There is a need for a quantitative myocardial perfusion agent that does not require an on-site cyclotron. Early studies with manganese demonstrated that this trace metal is of potential use for myocardial imaging. 52mMn can be produced in a 52Fe-52mMn generator and is suitable for positron emission tomographic (PET) imaging. The purpose of this study was to evaluate 52mMn with regard to its potential to quantitatively assess myocardial perfusion. Dynamic PET imaging was performed in six pigs with various doses of dipyridamole to increase blood flow. Retention (R) and model-based K1 values were correlated with microsphere blood flow. The models consisted of one (K1, k2) and two (K1, k2, k3) tissue compartments. Anterior, lateral and septal regions showed a good myocardium-to-background ratio; the evaluation of the inferior wall was impaired by high liver uptake. Linear regression yielded the following equations: K1=1.152 flow+0.059 (r=0.92), R=0.069 flow+0.034 (r=0.84). Based on these regressions, K1 increased 2.7-fold and R 2.6-fold in the examined flow range of 0.5-2 ml/min/g (fourfold increase), demonstrating an underestimation of higher flow rates by both measures. It is concluded that 52mMn allows the qualitative assessment of myocardial perfusion but does not meet the requirements of a quantitative myocardial perfusion agent.

Animals↗
PubMed1996

In vivo evaluation of epidermal growth factor (EGF) receptor density on human tumor xenografts using radiolabeled EGF and anti-(EGF receptor) mAb 425.

In order to study the potential of non-invasive scintigraphic evaluation of the epidermal growth factor (EGF) receptor status in vivo, the biokinetics and tumor binding of 125I-EGF and anti-(EGF receptor) mAb 425 were investigated in nude mice bearing human tumor xenografts with different EGF-receptor densities as determined by a radioreceptor assay. The results demonstrated a tumor uptake for both substances depending on the receptor level. The EGF receptor status, however, was reflected slightly better by the binding of EGF to tumor tissue compared to the mAb. The rapid blood clearance of EGF with a plasma half-life of less than 1 min led to a tumor-to-blood ratio of approximately 3 within 6 h after injection in tumors with a high receptor expression. A similar ratio for the mAb was not obtained before day 6 after injection. The absolute concentration of EGF, however, was low compared to the mAb. Therefore, it can be concluded that the EGF receptor status as a target for (radio)immunotherapy can be evaluated in vivo with EGF labeled with a short-life positron-emitting radionuclide or with monoclonal antibodies to the EGF receptor or their fragments.

Animals↗
PubMed1996

Oxygen tension in mouse mammary carcinomas and osteosarcomas after irradiation with reactor fission neutrons.

Investigations were made on intratumoral oxygen tension after irradiations with reactor fission neutrons using the Eppendorf-pO2-Histograph. Isotransplanted AT17-mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on Balb c-mice received 2 or 6 Gy neutrons single dose. Before and at certain points of time after treatment the pO2-values were evaluated. Some tumors with initially low median pO2-values showed a short-lasting increase between 2 and 24 hours after irradiation. In the tumors with relatively high median pO2-values before irradiation the pO2 decreased to hypoxic range. A third group of tumors showed no significant changes after irradiation. None of the tumors stopped growth during the observation period.

Adenocarcinoma↗
PubMedDate not supplied

Binding and uptake of 125iodine-labelled, oxidized low density lipoprotein by macrophages: comparison of the effects of alpha-tocopherol, probucol, pyridoxal-5'-phosphate and magnesium-pyridoxal-5'-phosphate-glutamate.

Specific and unspecific binding and uptake (internalization) by macrophages of 125iodine-labelled, copper-oxidized human low density lipoprotein is differently influenced by the anti-oxidants alpha-tocopherol (alpha-Toc), probucol (Prob), pyridoxal-5'-phosphate (PP) and the magnesium-pyridoxal-5'-phosphate glutamate complex (MPPG). Binding as well as internalization, mediated by the so-called "scavenger receptor" is lower in the presence of MPPG whereas both specific binding and internalization are enhanced. The comparison of the effects in vitro allows a rating of the potentially anti-atherogenic and thus protective effects of the tested substances as follows: MPPG > PP > alpha-Toc > Prob.

Animals↗
PubMedDate not supplied

Distribution of disialoganglioside GD2-antigen and binding of anti-GD2 antibodies on spheroids of neuroblastoma cell line.

The ganglioside GD2 is highly expressed on human tumors of neuroectodermal origin. We investigated by scanning electron microscopy the ganglioside GD2 distribution on the surface of spheroids of the neuroblastoma cell line SK-N-LO. About 50% of cells showed GD2 on the plasma membrane and the distribution of GD2 on most of these cells was heterogeneous, with more GD2 at the contact sites of the cells. The binding kinetics of the chimeric anti-GD2 antibody ch14.18 labelled with I-125 on spheroids (average diameter: 450 microns) was determined by gamma counting. Over 4 hours the antibody concentration was raised substantially but up to 24 hours there was only a very slow further increase. A clustered pattern of bound chimeric anti-GD2 antibody ch14.18 was found on a cross-section of the spheroid by autoradiography.

Antibodies, Monoclonal↗
PubMedDate not supplied

Growth inhibition of human papillary thyroid carcinoma cells and multicellular spheroids by anti-EGF-receptor antibody.

EGF has been reported to stimulate thyroid cell proliferation. In the present study we investigated the effects of anti-EGF-R-antibody (Mab 4253 both as monolayers and spheroids of an oxyphilic, non iodine metabolizing, papillary thyroid carcinoma cell line (ONCO-DG-1) and roughly characterized their EGF-R. Scatchard analysis with I-125-labeled-EGF demonstrated a low number of 1.5 x 10(4) EGF-R per monolayer cell (KD 4.1 X 10(-10) M) and only 6 x 10(3) EGF-R per spheroids cell (KD 5.0 X 10(-10) M). Already 80% of the binding sites were blocked by only 0.44 microgram/ml Mab 425. Proliferathe activity and EGF-R were found to be regularly distributed throughout the spheroids. Adding Mab 425 to medium containing 1 ng/ml EGF, inhibited the growth of monolayer cells by 15% (1 ng/ml Mab 425) and 28% (10 ngiml Mab 425), measured by the MTT-test. The volume growth of spheroids was inhibited by 10-15% using 2 micrograms/ml Mab 425, whereas their viability (MTT-Test) was almost identical. The results show that the anti-EGF-R-antibody (Mab 425) alone is not effective enough for therapeutical use, but it could be of clinical value in conjugation with radionuclides (e.g. I-131) in order to reach metastases not metabolizing iodine.

Animals↗
PubMedDate not supplied

Cytotoxic effect of immunoconjugate composed of glucose-oxidase coupled to an anti-ganglioside (GD2) antibody on spheroids.

As a new treatment protocol for neuroblastoma, the chimeric (human/mouse) antiganglioside GD2 antibody chl4.18 is being clinically tested. To improve the therapeutic effect of the antibody alone, we are currently investigating the cytotoxicity of glucose-oxidase coupled to the antibody chl4.18 on spheroids of the neuroblastoma cell line SK-N-LO. The cytotoxic effect of glucose-oxidase is achieved by the production of hydrogenperoxide (H2O2) and probably by the following reaction of H2O2 with iron to form hydrogen radicals (OH.). The cytotoxicity of glucose-oxidase was measured by two viability tests (MTT and WST 1). After a 4 hour treatment of the spheroids with the immunoconjugate, a reduction of viability to 50% (MTT-test) and 25% (WST 1-test), respectively, was obtained. The difference between the results of these two tests, might be explained by the different measurement protocols.

Antibodies, Monoclonal↗