Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors

BACKGROUND: Treatment with (90)Y- or (177)Lu-DOTATOC has recently been introduced in the palliative treatment of somatostatin receptor-expressing neuroendocrine tumors (NETs). The aim of the study was to present clinical experience with (90)Y- and (177)Lu-DOTATOC therapy in the management of NET. METHODS: To prove suitability for treatment each patient underwent scanning with (111)In-DTPAOC or (68)Ga-DOTATOC positron emission tomography/computed tomography. All patients received [(90)Y-DOTATOC] as initial treatment. In case of disease relapse the treatment was repeated. To avoid side effects of repeated [(90)Y] applications, a switch to [(177)Lu-DOTATOC] was carried out. Clinical, biochemical, and radioimaging responses were documented. RESULTS: Twenty patients with metastatic nonresectable NETs (15 pancreas NETs, 2 midgut NETs, 1 gastrinoma, 1 paraganglioma, 1 NET of unknown primary origin) were included. In 8 patients the treatment was repeated more than once (mean, 3 times; range, 2-5 times). After [(90)Y] treatment moderate toxicity was observed in 8 patients. No serious adverse events were documentable. After restaging, a partial remission was found in 5 patients, stable disease in 11 patients, and tumor progression in 4 patients. CONCLUSIONS: Peptide receptor-targeted radionuclide therapy is a promising, safe, and feasible approach in the palliative therapy of patients with NET.

Up-regulation of somatostatin receptor density on rat CA20948 tumors escaped from low dose [(177)Lu-DOTA(0),Tyr(3)]octreotate therapy

AIM: Peptide receptor radionuclide therapy using the somatostatin analogue [(177)Lu-DOTA(0),Tyr(3)]octreotate is a convincing treatment modality for metastasized neuroendocrine tumors. Therapeutic doses are administered in 4 cycles with 6-10 week intervals. A high somatostatin receptor density on tumor cells is a prerequisite at every administration to enable effective therapy. In this study, the density of the somatostatin receptor subtype 2 (sst2) was investigated in the rat CA20948 pancreatic tumor model after low dose [(177)Lu-DOTA(0), Tyr(3)]octreotate administration resulting in approximately 20 Gy tumor radiation absorbed dose, whereas 60 Gy is needed to induce complete tumor regression in these and the majority of tumors. METHODS: Sixteen days after inoculation of the CA20948 tumor, male Lewis rats were injected with 185 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate to initiate a decline in tumor size. Approximately 40 days after injection, tumors re-grew progressively after initial response. Quantification of sst2 expression was performed using in vitro autoradiography on frozen sections of three groups: control (not-treated) tumors, tumors in regression and tumors in re-growth. Histology and proliferation were determined using HE- and anti-Ki-67-staining. RESULTS: The sst2 expression on CA20948 tumor cells decreased significantly after therapy to 5% of control level. However, tumors escaping from therapy showed an up-regulated sst2 level of 2-5 times higher sst2 density compared to control tumors. CONCLUSION: After a suboptimal therapeutic dose of [(177)Lu-DOTA(0),Tyr(3)]octreotate, escape of tumors is likely to occur. Since these cells show an up-regulated sst2 receptor density, a next therapeutic administration of radiolabelled sst2 analogue can be expected to be highly effective.

Survival after somatostatin based radiopeptide therapy with (90)Y-DOTATOC vs. (90)Y-DOTATOC plus (177)Lu-DOTATOC in metastasized gastrinoma.

We aimed to explore the effects of (90)Y-DOTATOC and (90)Y-DOTATOC plus (177)Lu-DOTATOC on survival of patients with metastasized gastrinoma. Patients with progressive metastasized gastrinoma were treated with repeated cycles of (90)Y-DOTATOC or with cycles alternating between (90)Y-DOTATOC and (177)Lu-DOTATOC until tumor progression or permanent toxicity. Multivariable Cox regression analyses were used to study predictors of survival. A total of 36 patients were enrolled; 30 patients received (90)Y-DOTATOC (median activity per patient 11.8GBq; range: 6.1-62.2GBq) and 6 patients received (90)Y-DOTATOC plus (177)Lu-DOTATOC (median activity per patient: 14.8GBq; range: 7.4-14.8GBq). Response was found in 26 patients (72.2%), including morphological (n=12, 33.3%), biochemical (n=14, 38.9%) and/or clinical response (n=6, 16.2%). A total of 21 patients (58.3%) experienced hematotoxicity grade 1/2, while 1 patient (2.8%) experienced hematotoxicity grade 3; no grade 4 hematotoxicity occurred. Furthermore, 2 patients (5.6%) developed grade 4 renal toxicity; no grade 5 renal toxicity occurred. Responders had a significantly longer median survival from time of enrollment than non-responders (45.1 months, range: 37.1-53.1 months vs. 12.6 months, range: 11.0-14.2, hazard ratio: 0.12 (0.027-0.52), p=0.005). Additionally, there was a trend towards longer median survival with (90)Y-DOTATOC plus (177)Lu-DOTATOC as compared to (90)Y-DOTATOC alone (60.2 months, range: 19.8-100.6 months vs. 27.0 months, range: 4.0-50.0, hazard ratio: 0.21 (0.01-3.98), p=0.16). Response to (90)Y-DOTATOC and (90)Y-DOTATOC plus (177)Lu-DOTATOC therapy is associated with a longer survival in patients with metastasized gastrinoma. Both treatment regimens are promising tools for management of progressive gastrinoma.

Ms. Barth. 177 - [Sammelband in 7 Teilen: Konvolut aus Handschriften und Inkunabeln]

Vorbesitzer: Bartholomaeusstift Frankfurt am Main

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 177 - Dankesschreiben wegen der Zusendung der Dissertation

u.a.: Dissertation Schopenhauers; Über die vierfache Wurzel des Satzes vom zureichenden Grunde; Analyse über den geistigen Zustand der Studentenschaft in Deutschland; Habilitation Schopenhauers; Doktorprüfung; August Wilhelm Schlegel; Prof. Schweins, Dekan der philosophischen Fakultät Heidelberg; Zahn;

Ms. Praed. 177 - Dominikanergebetbuch

Vorbesitzer: Dominikanerkloster Frankfurt am Main

Ms.Ff.F.Stoltze 3. 177 - Brief von Siegmund Leopold Kohn-Speyer an Friedrich Stoltze

Johann Albrecht Varrentrapp, Sauerländer, Tod Ernst Schalcks

Na 1 Nachlass Max Horkheimer, 370 - Korrespondenzen u.a. mit Ludwig Neundörfer und Oskar Negt (p. V 128, 1-177)

2 Briefe zwischen der Buchhandlung Peter Naacher und Max Horkheimer, 1966-1968; 1 Brief von E. Nabulon an Max Horkheimer, 1971; 13 Briefe und Beilage zwischen dem Dozenten Georg Nádor und Max Horkheimer, 1964-1967; 4 Briefe zwischen Cornelia Nass und Max Horkheimer sowie der Beilage: Vortrag von Val. Giscard d'Estaing über "die neue Gesellschaft" Brüssel 1970, 1970-1972; 6 Briefe zwischen Else Nassauer und Max Horkheimer, 1967-1973; 3 Briefe zwischen S.Andhil Fineberg und Max Horkheimer, 1967-1969; 1 Brief von Dr. med. Horst Naujoks an Max Horkheimer, 1963; 3 Briefe von Max Horkheimer an die Zeitschrift Nebelspalter, 1964-1969; 7 Briefe zwischen Max Horkheimer und Carl Nedelmann, 1964; 2 Briefe und Beilage zwischen Dr. Renate Neef-Cramer und Max Horkheimer, 1972; 3 Briefe zwischen Walter Neef und Max Horkheimer, 1965; 1 Brief an Dr. Oskar Negt von Max Horkheimer, 1964; 9 Briefe zwischen Dr. Günther Nenning und Max Horkheimer, 1962-1972; 4 Briefe zwischen der Neuen Deutschen Biographie und Max Horkheimer, 1969-1970; 4 Briefe und Beilage zwischen der Wochenschrift Neue Politik und Max Horkheimer, 1971; 6 Briefe zwischen Joachim Günther und Max Horkheimer, 1969-1970; 10 Briefe zwischen der Neuen Rundschau Rudolf Hartung und Max Horkheimer, 1964-1968; 1 Brief an Heinz Friedrich von Max Horkheimer, 1969; 9 Briefe zwischen Dr. Günther Nenning und Max Horkheimer, 1969-1972; 4 Briefe zwischen dem Rektor Günther Neuhardt und Max Horkheimer, 1970; 7 Briefe zwischen Rexa Neumeister und Max Horkheimer, 1967; 28 Briefe und Beilage zwischen dem Professor Ludwig Neundörfer und Max Horkheimer, 1955-1971; 1 Brief an den Professor John J. Neunaier von Max Horkheimer, 1965; 2 Briefe zwischen der Newton Compton Editori und Max Horkheimer, 1970; 3 Briefe zwischen der New York Times und Max Horkheimer, 1959-1960; 4 Briefe und Beilage zwischen Stephen Ney und Max Horkheimer, 1967; 4 Briefe und Beilage zwischen dem Student Claus Niederberger und Max Horkheimer, 1973; 1 Brief an Dr. Friedrich Niewöhner von Max Horkheimer, 1973; 4 Briefe zwischen dem Professor August Nietschke und Max Horkheimer, 1965; 1 Dankesbrief von N.N. an Maidon Horkheimer, 1963; 1 Brief [Hinweis auf eine Krebstherapie] von N.N. an Max Horkheimer; 1 Brief [gegen den Kommunismus] von N.N. an Max Horkheimer, 1955; 1 Brief [Ansichtskarte, Unterzeichnet mit D.C.] von N.N. an Max Horkheimer, 1953; 1 Telegramm [Mitteilung über Schiffverbindung] von N.N. an Max Horkheimer, 1949; 3 Briefe und Beilage zwischen dem Northern Life Insurance Co. Seattle, Wash. und Max Horkheimer, 1951-1953; 4 Briefe und Beilage zwischen den Nürnberger Nachrichten und Max Horkheimer sowie einem Interview mit Max Horkheimer, 1973; 1 Brief von der Nymphenburger Verlagshandlung an Max Horkheimer, 1968;

Ms. lat. oct. 177 - Sammelhandschrift des Frankfurter Pfarrers Bernhard Waldschmidt

Vorbesitzer: Bernhard Waldschmidt

Plio-Pleistocene diatom biostratigraphy from ODP Leg 177, Atlantic sector of the Southern Ocean

Seven sites were drilled during Ocean Drilling Program Leg 177 in the Atlantic sector of the Southern Ocean (SO) on a transect over the Antarctic Circumpolar Current from the Subantarctic to the Antarctic Zone. At four sites sediments were recovered with a Pliocene/Pleistocene sediment package of up to 580 m allowing the refinement of previous diatom zonation concepts. Samples were analyzed on stratigraphic distribution and abundance of diatom species. A refined diatom biozonation tied to the geomagnetic polarity record is proposed. For the middle and late Pleistocene two zonations applicable to the northern and southern area of the SO were constructed, considering different latitudinal distributions of biostratigraphic diatom marker species. The southern zonation for the Pleistocene relies on the occurrence of species of the genus Rouxia, R. leventerae and R. constricta n. sp. as well as on a revised last occurrence datum (LOD) of Actinocyclus ingens (0.38 Ma, late marine isotope stage (MIS) 11). The use of these new stratigraphic marker species refines the temporal resolution for biostratigraphic age assignment to up to 0.1 Myr. In particular the LOD of R. leventerae as an indicator for the MIS 6/5 boundary (Termination II) will improve future dating of carbonate-free Antarctic sediments. These new data were obtained from sediments of Sites 1093 and 1094 (Antarctic Zone). The northern zonation for the middle and late Pleistocene time interval is based on the Pleistocene abundance pattern of Hemidiscus karstenii which was already proposed by previous investigations (e.g. Gersonde and Barcena, 1998). One new species (R. constricta) and two new combinations (Fragilariopsis clementia, Fragilariopsis reinholdii) are proposed in this study.

Relative abundance and ranges of selected diatoms from Pliocene-Pleistocene sections of ODP Leg 177, Atlantic sector of the Southern Ocean

During Ocean Drilling Program (ODP) Leg 177, seven sites were drilled aligned on a transect across the Antarctic Circumpolar Current in the Atlantic sector of the Southern Ocean. The primary scientific objective of Leg 177 was the study of the Cenozoic paleoceanographic and paleoclimatic history of the southern high latitudes and its relationship with the Antarctic cryosphere development. Of special emphasis was the recovery of Pliocene-Pleistocene sections, allowing paleoceanographic studies at millennial or higher time resolution, and the establishment of refined biostratigraphic zonations tied to the geomagnetic polarity record and stable isotope records. At most sites, multiple holes were drilled to ensure complete recovery of the section. A description of the recovered sections and the construction of a multihole splice for the establishment of a continuous composite is presented in the Leg 177 Initial Reports volume for each of the sites (Gersonde, Hodell, Blum, et al., 1999). Here we present the relative abundance pattern and the stratigraphic ranges of diatom taxa encountered from shore-based light microscope studies completed on the Pliocene-Pleistocene sequences from six of the drilled sites (Sites 1089-1094). No shore-based diatom studies have been conducted on the Pliocene-Pleistocene sediments obtained at Site 1088, located on the northern crest of the Agulhas Ridge, because of the scattered occurrence and poor preservation of diatoms in these sections (Shipboard Scientific Party, 1999b). The data included in our report present the baseline of a diatom biostratigraphic study of Zielinski and Gersonde (2002), which (1) includes a refinement of the southern high-latitude Pliocene-Pleistocene diatom zonation, in particular for the middle and late Pleistocene, and (2) presents a biostratigraphic framework for the establishment of age models of the recovered sediment sections. Zielinski and Gersonde (2002) correlated the diatom ranges with the geomagnetic polarity record established shipboard (Sites 1090 and 1092) (Shipboard Scientific Party, 1999c, 1999d) and on shore (Sites 1089, 1091, 1093, and 1094) by Channell and Stoner (2002). The Pliocene-Pleistocene diatom zonation proposed by Zielinski and Gersonde (2002) relies on a diatom zonation from Gersonde and Bárcena (1998) for the northern belt of the Southern Ocean. Because of latitudinal differentiation of sea-surface temperature, nutrients, and salinity between Antarctic and Subantarctic/subtropical water masses, the Pliocene-Pleistocene stratigraphic marker diatoms are not uniformly distributed in the Southern Ocean (Fenner, 1991; Gersonde and Bárcena, 1998). As a consequence, Zielinski and Gersonde (2002) propose two diatom zonations for application in the Antarctic Zone south of the Polar Front (Southern Zonation, Sites 1094 and 1093) and the area encompassing the Polar Front Zone (PFZ) and the Subantarctic Zone (Northern Zonation, Sites 1089-1092). This accounts especially for the Pleistocene zonation where Hemidiscus karstenii, whose first abundant occurrence datum and last occurrence datum defines the subzonation of the northern Thalassiosira lentiginosa Zone, occurs only sporadically in the cold-water realm south of the PFZ and thus is not applicable in sections from this area. However, newly established marker species assigned to the genus Rouxia (Rouxia leventerae and Rouxia constricta) are more related to cold-water environments and allow a refinement of the Pleistocene stratigraphic zonation for the southern cold areas. A study relying on quantitative counts of both Rouxia species confirms the utility of these stratigraphic markers for the identification of sequences attributed to marine isotope Stages 6 and 8 in the southern Southern Ocean (Zielinski et al., 2002).