Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers

Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes.

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.