Evaluation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated bombesin-based radioantagonist for the labeling with single-photon emission computed tomography, positron emission tomography, and therapeutic radionuclides

PURPOSE: G protein-coupled receptor agonists are being used as radiolabeled vectors for in vivo localization and therapy of tumors. Recently, somatostatin-based antagonists were shown to be superior to agonists. Here, we compare the new [111In/68Ga]-labeled bombesin-based antagonist RM1 with the agonist [111In]-AMBA for targeting the gastrin-releasing peptide receptor (GRPR). EXPERIMENTAL DESIGN: IC50, Kd values, and antagonist potency were determined using PC-3 and HEK-GRPR cells. Biodistribution and imaging studies were done in nude mice transplanted with the PC-3 tumor. The antagonist potency was assessed by evaluating the effects on calcium release and on receptor internalization monitored by immunofluorescence microscopy. RESULTS: The IC50 value of [(nat)In]-RM1 was 14 +/- 3.4 nmol/L. [(nat/111)In]-RM1 was found to bind to the GRPR with a Kd of 8.5 +/- 2.7 nmol/L compared with a Kd of 0.6 +/- 0.3 nmol/L of [111In]-AMBA. A higher maximum number of binding site value was observed for [111In]-RM1 (2.4 +/- 0.2 nmol/L) compared with [111In]-AMBA (0.7 +/- 0.1 nmol/L). [(nat)Lu]-AMBA is a potent agonist in the immunofluorescence-based internalization assay, whereas [(nat)In]-RM1 is inactive alone but efficiently antagonizes the bombesin effect. These data are confirmed by the calcium release assay. The pharmacokinetics showed a superiority of the radioantagonist with regard to the high tumor uptake (13.4 +/- 0.8% IA/g versus 3.69 +/- 0.75% IA/g at 4 hours after injection. as well as to all tumor-to-normal tissue ratios. CONCLUSION: Despite their relatively low GRPR affinity, the antagonists [111In/68Ga]-RM1 showed superior targeting properties compared with [111In]-AMBA. As found for somatostatin receptor-targeting radiopeptides, GRP-based radioantagonists seem to be superior to radioagonists for in vivo imaging and potentially also for targeted radiotherapy of GRPR-positive tumors.

Na 1 Nachlass Max Horkheimer, 645 - "Geschichte und Psychologie", "Preface" und "Vorurteil und Charakter" (p. IX 25a-IX 27.1-4)

"Geschichte und Psychologie" (GS 3, S. 48-69); Photokopie des Drucks aus der Zeitschrift für Sozialforschung, Jahrgang I, 1932; mit handschriftlichen Korrekturen von Gretel Adorno für den Nachdruck (1968), 11 Blatt; "Preface" to Berkeley Adult Study (GS 5, S. 415-420); Veröffentlicht in: Adorno, Theodor W.; Frenkel-Brunswik, Else; Levinson, Daniel J.; Sanford, R. Nevitt: "The Authoritian Personality", New York, 1950, Seote IX- XII. Typoskript, datiert: April 1948, 8 Blatt (siehe auch IX 140, IX 153.3); "Vorurteil und Charakter" (GS 8, Seite 64-76); 1. Aufsatz von Max Horkheimer und Theodor W. Adorno, veröffentlicht in: Frankfurter Hefte; April 1952, Seite 284-291. a) Teilstück, Typsokript, 2 Blatt b) Typoskript mit eigenhändigen und handschriftlichen Korrekturen, 14 Blatt c) Typoskript mit dem Titel: "Vorurteil: Wissenschaftlich untersucht. Der freie und der totalitäre Mensch"; mit handschriftlichen Korrekturen, 5 Blatt d) Typsokript mit demselben Titel, mit eigenhändigen Korrekturen von Max Horkheimer und Theosodr W. Adorno, 6 Blatt; 2. Englische Fassung mit dem Titel: "Prejudice and Personality". a) Typoskript, 14 Blatt b) Typoskript, 14 Blatt; 3. Horkheimer, Max: "Prejudice and Personality. A Paper prepared for the XII th Congress of the International Association of Allied Psychology as a Contribution to the Symposion on: 'The Psychologist ams Scienty'". London, July 19, 1955; 2. überarbeitete Fassung, Typoskript, 7 Blatt; 4. "Vorurteil"; größtenteils identisch mit 1. Typsokript, 10 Blatt (siehe auch IX 28.8);

Na 1 Nachlass Max Horkheimer, 654 - "The Aftermath of National Socialism"; "National Socialism and Philosophy"; "The Idea of Philosophy"; "Programm einer Intereuropäischen Akademie" (p. IX 36a.1-4-IX 39.1-2)

"The Aftermath of National Socialism. On the Cultural Aspects of the Collapse of National Socialism". Vorlesungsreihe des Instituts für Sozialforschung, März 1945; 1. Vorlesungsankündigung und Typoskripte der Beiträge von: Theodor W. Adorno, "The Fate of the Arts" (= "What National Socialism Has Done to the Arts"); Frederick Pollock, "Prejudice and the Social Classes"; Leo Löwenthal, "The Aftermath of Totalitarian Terror". Bibliographie, Typoskripte, geheftet, mit eigenhändiger Korrektur von Frederick Pollock, 93 Blatt; 2. Vorlesungsankündigung, als Typoskript vervielfältigt, 1 Blatt; 3. Max Horkheimer: "Totalitarism and the Crisis of European Culture". Eigene Notizen zur Vorlesung, 3 Blatt; 4. Theodor W. Adorno: Notizen zur Vorlesungsreihe. Typoskript, 2 Blatt; Max Horkheimer: "National Socialism and Philosophy". Seminar Frühjahr 1945; 1. Protokolle zu den Sitzungen vom 5.2, 24.4., 1.5. und 8.5.1945. Typoskript mit eigenhändiger Korrektur, 16 Blatt; 2. Dasselbe. Gebunden, 16 Blatt; 3. Eigenhändige Notizen, 8 Blatt; Max Horkheimer: "The Idea of Philosophy". Vorlesung Winter 1945/46; 1. Eigenhändige Notizen, 3 Blatt; 2. Eigenhändige Notizen, 4 Blatt; 3. Eigenhändige Notizen, 2 Blatt; 4. Abschriften aus Werken unter anderem von Friedrich von Bezold, Karl Lamprecht, Richard Pietchman, Leopold von Ranke, Edwin R.A. Seligman. Typoskripte, 8 Blatt; 5. Paul Tillich: "Conscience in Western Thought and the Idea a Transmoral Conscience". Sonderdruck aus: Crozer Quarterly, Vol. XXII, Nr. 4, Oktober 1945, 6 Blatt; Max Horkheimer: Programm einer Intereuropäischen Akademie, 1944/45 (?); 1. Typoskriptfassungen, englisch. a) Typoskript, 18 Blatt b) Typoskript mit handschriftlicher Korrektur von Theodor W. Adorno (GS 12, S.195-213), 18 Blatt c) Typoskript (Kopie) mit handschriftliche Korrektur, 18 Blatt (Kopie 1989 aus der Hoover Institution, Standford, California) d) Typoskript mit eigenhändiger Korrektur, 17 Blatt e) Korrektur-Teilstücke, Typoskripte mit eigenhändiger Korrektur, 2 Blatt; 2. Zeitungsausschnitt 1944, 1 Blatt;

Rede, gehalten bei dem Trauerg[o]ttesdienst zum Gedächtniss des seligen Freiherrn Wilhelm Carl von Rothschild in der Synagoge zu Lübeck, am Sonntag, den 14. Schwat 5661 (3. Febr. 1901), Nachm. 4 Uhr

von S. Carlebach

Ichthyoplankton density and zooplankton biomass in the Benguela upwelling system during MSM17/3 in January and February 2011

Ichthyoplankton density (fish eggs and larvae) and bulk zooplankton biomass in January/February 2011 were determined for 38 stations in the northern Benguela upwelling system, based on oblique Multinet hauls during the FS Maria S. Merian MSM17/3 cruise. A HYDROBIOS Multinet, type Midi (0.25 m**2 mouth area) was equipped with five nets of 500 µm-mesh size, temperature and oxygen probes, and an inner and outer flow meter to monitor the net's trajectory (for volume filtered calculations) as well as net clogging. The Multinet was handled over the side, towed horizontally at 2 knots. Winch speed when fearing was 0.5 or 0.3 m/s, heaving velocity 0.2 - 0.3 m/s. The Multinet was towed obliquely at 38 stations sampling the upper 200 m of the water column, which were divided into five different depth strata after inspection of temperature and oxygen concentration depth profiles. Ichthyoplankton densities and zooplankton biomass were calculated for each depth stratum (=single net) from total abundance and the volume of water filtered [individuals per m**3 and g wet weight per m**3, respectively]. In addition, densities and biomass were integrated over the area for each station [individuals per m**2], as sum of calculations for each net: Sum ([individuals per m**3]*Delta (depth bot[m]-depth top [m]).