Hamburg 1 ist ein privater Hamburger Regional-Fernsehsender. Er hat eine technische Reichweite von zirka 1,9 Millionen Haushalten und sendet über die Grenzen der Stadt hinaus, per Kabel bis Kaltenkirchen, Büchen, Harsefeld und Lüneburg. Er ist. Informationen über Cookies auf dieser Website. Um unsere Webseite für Sie optimal zu gestalten und fortlaufend verbessern zu können, verwenden wir Cookies. Hamburg 1 ist ein privater Hamburger Regional-Fernsehsender. Er hat eine technische Reichweite von zirka 1,9 Millionen Haushalten und sendet über die. HH1 Sendungen. Gestern; heute; Sa; So; Mo; Di; Mi; Do; diese Woche; nächste Woche; 14 Tage. Das aktuelle TV-Programm vom Do nur Tipps nur Live-. Der Hamburger Stadtsender Hamburg 1 zeigt Nachrichten aus Politik, Wirtschaft, Kultur und Sport sowie Magazine, Reportagen und Talkshows.
Hamburg 1 ist ein privater Lokalsender, der sich mit Inhalten rund um die Hansestadt beschäftigt. Wir zeigen euch, wie ihr Hamburg 1 als Live-Stream direkt im. Ihr habt eine Sendung auf Hamburg 1 verpasst oder wollt sie mit euren Bekannten teilen? In unserem Sendungsarchiv findet ihr alle Sendungen der letzten 2. Alle Sendungen bei Hamburg 1 - das gesamte Hamburg 1 TV-Programm von heute auf einen Blick. Alle Sendungen bei Hamburg 1 - das gesamte Hamburg 1 TV-Programm von heute auf einen Blick. Das TV Programm von HH1 für heute und Uhr. Das Fernsehprogramm für den Sender HH1 bei TV Movie. Hamburg 1 ist ein privater Lokalsender, der sich mit Inhalten rund um die Hansestadt beschäftigt. Wir zeigen euch, wie ihr Hamburg 1 als Live-Stream direkt im. Abb. HH2, S. 36r Der ungleich stärkere Grund ist allerdings darin zu sehen, dass die in Genf aufbewahrte Fassung GE, die ja nach HH1 und HH2 abgefasst. Ihr habt eine Sendung auf Hamburg 1 verpasst oder wollt sie mit euren Bekannten teilen? In unserem Sendungsarchiv findet ihr alle Sendungen der letzten 2. TNT Film. Tom hardy Television. Spiegwl Mehr zu den technischen Besonderheiten erfahrt ihr hier. Namensräume Hh1 Diskussion. Dabei gibt es auch lokale Formate wie das hamburgische Frühstücksfernsehen mit Beiträgen aus der Region und über aktuelle Ereignisse, etwa dem Here, in der Hansestadt. Lob, Kritik, Vorschläge. Hamburg 1 Programm. SRF info.
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Learn more - opens in a new window or tab. There are 1 items available. Radio-immunotherapy RIT with CD37 as the target has previously been explored using a I-labeled murine monoclonal antibody MB-1 both in a mouse model and in patients  — .
Despite promising clinical responses observed in these clinical studies, further development of RIT focused on CD20 as the target antigen. Iodine labeled via chloramine-T is a non-residualizing radionuclide which may be sub-optimal when targeting an internalizing antigen .
It is produced by direct neutron activation of Lu, or via beta decay of reactor-produced Yb and it is commercially available in GMP quality  , .
The energy of the beta particle of Lu is relatively low, resulting in a shorter range in tissues compared to other beta-emitters used for RIT .
Severe Combined Immunodeficiency SCID mice, intravenously injected with Daudi lymphoma cells that developed tumors in the spine, lymph nodes, kidneys and lungs were successfully treated with Lu-HH1 .
However, higher absorbed radiation doses will most probably be necessary for curative treatment of macroscopic tumors.
It is therefore mandatory to study the toxicity of Lu-HH1 in a mouse strain that has intact DNA-damage-repair capability, such as conventional nude mice, where higher doses can be given and relevant therapeutic effects may be obtained.
Although tumor models based on SCID mice might be interesting tools  , their radiation sensitivity might lead to results that are more distant from reality than more conventional models.
The current paper evaluates the toxicity of Lu-HH1 in nude mice. Studying systemic toxicity of this newly developed RIC will guide in establishing a safe starting dosage for clinical trials and may give an indication of the potential side effects to be monitored during Phase I clinical trials.
Before labeling with Lu the pH was adjusted to 5. The radiochemical purity RCP of the conjugate was evaluated using instant thin layer chromatography.
The immunoreactivity of the RIC was measured using a modified Lindmo method . Institutionally bred female athymic nude mice were used in the experiments Table 1.
Food and water were supplied ad libitum and bedding was changed regularly. All procedures and experiments involving animals in this study were approved by the Norwegian Animal Research Authority and carried out according to the European Convention for the Protection of Vertebrates Used for Scientific Purposes.
Four different experiments were performed Table 1. One cage per treatment group was used. Mice were allocated in the cages so that the tumor size distribution was similar in each group.
In experiment 1, 8 mice in each group were treated with a single administration of 0. The mice in this experiment were initially implanted with Daudi tumors, but the take was low and the mice in which the tumors did not grow were selected for the experiment.
These mice were considered to be without tumor. In experiment 2, groups of 10 mice without tumor xenografts were treated with a single administration of either 0.
Half of the mice were monitored for 6 months and half for 10 months post-injection. In experiment 3, nude mice with Ramos lymphoma xenografts were treated with a single administration of 0.
Mice were followed for 4 to 6 weeks. In experiment 4, 9 or 10 mice with Ramos lymphoma xenografts were treated with a single administration of 0.
Mice were euthanized by neck dislocation whenever an end point was reached or when the experiment was finalized. The mice were weighed and evaluated clinically three times a week.
Tumor size was measured 2 to 3 times a week using an electronic caliper in 2 dimensions. In some mice from experiment 4, blood samples were taken by heart puncture under gas anesthesia Sevofluorane, Abbot, Abbot Park, IL.
All statistical analyses were performed using the software SigmaPlot Where multiple comparisons were required, the Holm-Sidak method for all multiple pairwise comparisons was used.
Statistical analysis of the hematology and clinical chemistry data was performed using Student t-test with 0. Louis, USA, , processed for histological examination and embedded in paraffin wax.
Histological sections were stained with hematoxylin and eosine and examined microscopically. In experiment 4 fewer organs were sampled: heart, lungs, liver, stomach, spleen, small intestine, large intestine, kidneys, femur, muscle, thyroid, skull, brain, tumor, urinary bladder skin, ovaries and lymph nodes.
None of these mice were euthanized due to suspected radiation toxicity no symptoms of sickness or discomfort or WBC lower than 1.
The end point for survival was euthanasia due to weight loss or substantial discomfort. Mice euthanized because of tumor diameter larger than 20 mm were censored.
The mice were euthanized if the WBC was lower than 1. In experiment 3, there were no statistical differences in survival between any of the groups data not shown.
The reason for this result was that the mice in the control group were euthanized due to tumor size and therefore censored out of the survival analysis.
The results for tumor growth will be reported elsewhere. WBC, RBC and platelets were measured before injection and at several time points after injection in experiments 1 and 2, and before injection and at euthanasia in experiments 3 and 4.
Blood samples were taken before treatment, 1 month after treatment and at euthanasia. The weight loss was severe after 10 days, which was considered to be an indirect symptom of radiation toxicity since no deleterious changes to the gastrointenstinal system were observed.
The weight loss was probably related to less food intake of sick mice. Error Bars: Standard deviation. Blood samples were taken before treatment and at euthanasia.
There were no significant changes in the urea values. The changes in the serum concentrations of these liver enzymes might indicate liver damage.
This explains the large error bars at this time point in Figure 4A. This mouse did not show any symptoms of illness or discomfort, hematology values were normal, and it was euthanized at the end of the experiment, not due to any clinical signs or symptoms.
Hematology values were normal. The mouse was euthanized at this time point due to weigh loss and rectal prolapse.
The main organs affected were the bone marrow, lymph nodes, spleen and ovaries Table 2 , Figure 5.
Normal spleen from a control mouse. Normal lymph node from a control mouse showing diffuse interstitial cell hyperplasia.
This is a common background finding noted in the lymph nodes from athymic nude mice. Normal bone marrow from a control mouse. These changes were considered to be non-specific changes related to the increased susceptibility of nude mice to infections.
However, the presence of microscopic lymphoma infiltration was observed in spleen, lymph nodes, pancreas or liver in both control and treated mice from experiment 1, with a slightly decreased incidence in treated animals.
This change was characterized by the presence of dense sheets of round to polygonal cells up to 40 micrometers in diameter.
The lymphoma infiltration was probably due to lymphoma cells from the subcutaneous xenografts with which these mice were originally implanted.
We have previously shown good therapeutic effects of Lu-HH1 in SCID mice  and relatively high tumor uptake and low normal tissue uptake in nude mice .
The expected target organ for toxicity of Lu-HH1 is bone marrow due to retention of the RIC in the blood and, binding to tumor cells if present, in the bone marrow.
The toxicity is expected to be transient since normal stem cells do not express CD37 and will therefore be damaged only by cross-fire radiation and not by direct radiation from bound RIC.
The study indicates that the dose limiting organ is the bone marrow. This finding is in agreement with previous studies showing that the most common and dose-limiting side effect of RIT in lymphoma is bone marrow toxicity .
In addition, both the MTD and the dose-limiting organ observations are in good agreement with results from another study of Lu-CC49 a murine IgG 1 reactive with the tumor-associated antigen TAG .
It is, therefore, apparent that Lu-labeled antibodies are more toxic for SCID mice than for nude mice.
The reason why the MTD for humans is more similar to the MTD for SCID mice than for nude mice may be related to differences in DNA repair capacity between rodent and human cells, or it could be attributed to the large differences in tumor targeting and normal tissue uptake and retention between rodents and humans.
HH1 is not cross reactive to mouse B-cells and hence, only non-specific binding of the RIC and cross-radiation from specifically bound RIC to the tumor xenograft will contribute to the absorbed radiation dose in nude mice.
Ovarian atrophy and interstitial cell hyperplasia were observed in some of the treated animals. The interstitial cell hyperplasia has been reported to accompany ovarian atrophic changes  , .
The present study does not allow to conclude if these changes are age-related or if there is any contribution from the Lu-HH1 treatment.
We hypothesize that the increase in ovary atrophy observed in the treated animals could be related to the radiation dose to ovaries due to cross-fire radiation from the kidneys, where Lu-HH1 has a modest uptake .
The ovaries are separated from the kidneys by a thin layer of fat so that part of the beta-radiation from Lu in the kidneys can reach the ovaries, since the maximum range of the beta-radiation is 1.
If this is the cause of the changes observed in mouse ovaries, this effect should not be expected in humans.
The dose-limiting toxicity occurred in the bone marrow and manifested as low blood cell counts a few weeks after administration of the RIC.
The long term follow up data indicated only modest late toxicity in this murine model of human B-cell NHL. The toxicity profile of Lu-HH1 presented in this paper, combined with the previously published study demonstrate that Lu-HH1 has a similar biodistribution in nude mice to that of the clinically tested Lu-rituximab  , .
This study suggests that Lu-HH1 is suitable for clinical evaluations. The dose-limiting toxicity occurred in the bone marrow and manifested itself as low blood cell counts a few weeks after administration of the RIC followed by a return to normal ranges.