Copper-64 Labeled Macrobicyclic Sarcophagine Coupled to a GRP Receptor Antagonist Shows Great Promise for PET Imaging of Prostate Cancer

The gastrin-releasing peptide receptor (GRPr) is an important molecular target for the visualization and therapy of tumors and can be targeted with radiolabeled bombesin derivatives. The present study aims to develop statine-based bombesin receptor antagonists suitable for labeling with 64Cu for imaging by positron emission tomography (PET). The potent GRPr antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 was conjugated to the sarcophagine (3,6,10,13,16,19-hexaazabicyclo[6.6.6] icosane=Sar) derivative 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar) via PEG4 (LE1) and PEG2 (LE2) spacers and radiolabeled with 64Cu2+ with >95% yield and specific activities of about 100 MBq/nmol. Both Cu(II) conjugates have high affinity for GRPr (IC50: natCu-LE1, 1.4±0.1 nM; natCu-LE2, 3.8±0.6 nM). The antagonistic properties of both conjugates were confirmed by Ca2+-flux measurements. Biodistribution studies of Cu-64-LE1 exhibited specific targeting of the tumor (19.6±4.7% IA/g at 1 h p.i.) and GRPr-positive organs. Biodistribution and PET images at 4 and 24 h postinjection showed increasing tumor-to-background ratios with time. This was illustrated by the acquisition of PET images showing high tumor-to-normal tissue contrast. This study demonstrates the high affinity of the MeCOSar-PEGx-bombesin conjugates to GRPr. The stability of 64Cu complexes of MeCOSar, the long half-life of 64Cu, and the suitable biodistribution profile of the 64Cu-labeled peptides lead to PET images of high contrast suitable for potential translation into the clinic.

Life style habits such as alcohol consumption and physical activity in relation to serum apoB / apoA-I ratio amongst 64-year-old women with varying degrees of glucose tolerance.

OBJECTIVES To investigate how life style factors such as alcohol consumption and physical activity relate to the serum apoB / apoA-I ratio in a cohort of middle-aged women with varying degrees of glucose tolerance. DESIGN Observational, cross-sectional cohort study. SETTING Research laboratory at a University Hospital. SUBJECTS A screened cohort of 64-year-old postmenopausal women with varying degrees of glucose tolerance, ranging from diabetes (n = 232), impaired (n = 212) and normal (n = 191) glucose tolerance. MAIN OUTCOME MEASURE ApoB / apoA-I ratio in relation to alcohol consumption and physical activity as assessed by questionnaires. RESULTS Alcohol consumption and regular physical activity at high levels were inversely associated with the serum apoB / apoA-I ratio independently of confounding factors such as obesity, lipid-lowering treatment, degree of glucose tolerance and hormone replacement therapy. Alcohol seemed related to the apoB / apoA-I ratio mainly through increasing apoA-I, whereas physical activity seemed mainly related to lowering of apoB. Alcohol consumption above a daily intake of 8.9 g, i.e. less than a glass of wine was accompanied by a decrease in apoB / apoA-I ratio. CONCLUSIONS Amongst these 64-year-old women with varying degrees of glucose tolerance, a moderate alcohol intake and regular physical exercise leading to sweating were associated with lower apoB / apoA-I ratio and these effects seem to be additive.

Randglossen zum dem Aufsatze von Klein: "Zur Ortsnamenkunde Palästinas" [Nachricht] : (Monatsschrift 64, 123 ff.)

Jakob Nachum Epstein

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 64 - Vereherungsschreiben der Schriftstellerin Jeanne Marie von Gayette

u.a.: Rezension der Frauenstädtschen ?Briefe über die Schopenhauersche Philosophie", Grenzboten 1854, Nr. 9; Studium der "Welt als Wille und Vorstellung" in der Universitätsbibliothek Berlin; Professor Werder; Polemik gegen Goethe und Hegel; Professor Karl Ernst Schubarth (1796?1861), Philologe und Ästhetiker in Berlin, zuletzt Gymnasialprofessor in Hirschberg; Dr. Pomtow, Verfasser der Abhandlung ?über die Immanenz des Willens in den Dingen und in der Seele. Ein Versuch, die Frage: Wie ist das Erkennen möglich? nach Arthur Schopenhauers Principien zu lösen." (Programm des Joachim sthalschen Gymnasiums zu Berlin vom 29. September 1854); Colnische Zeitung; Berliner Zeitung; H. Fichte; Julius Frauenstädt;

Ms. Praed. 64 - Summa de summo bono I-IV

Vorbesitzer: Jakob Heller; Dominikanerkloster Frankfurt am Main

Ms.Ff.F.Stoltze 3. 64 - Brief von Rudolf Fendt an Friedrich Stoltze

A. Voemelsche Buchhandlung, Beschwerde über Nicht-Antwort, Ernst Emmerling, Leopold Sonnemann

Fragm. lat. IX 64 - Schuldschein, Bücher betreffend

Trägerband: Inc. gr. fol. 3 Bd. 3; Vorbesitzer: Dominikanerkloster Frankfurt am Main

Ms. lat. oct. 64 - Doctrina de sterilitate eiusque caussis, signis, et curatione

Vorbesitzer: Johann Hartmann Beyer

Fragm. lat. I 64 - Homiliarium (De tempore, Pars hiemalis)

Trägerbände: Inc. qu. 664 Bd. 3; Inc. qu. 1226; Inc. qu. 1248; Inc. oct. 120; Inc. oct. 236; Inc. oct. 321; Inc. oct. 429; Inc. oct. 441; Inc. oct. 442; 'Textus Sententiae'; Vorbesitzer: Dominikanerkloster Frankfurt am Main

Inc. hebr. 64 - Sefer ha-maḥbarot

Vorbesitzer: Jacob Kirgberger;

64 Rollenbilder aus Bayreuth, 1891, mit Durchstreichungen

Signatur des Originals: S 36/F12186

Na 1 Nachlass Max Horkheimer, 659 - Berichte über die Arbeit des Instituts für Sozialforschung u.a. (p. IX 64-IX 65b)

"The International Institute of Social Research. Its History, Program and Needs" (1943?), als Typoskript vervielfältigt, 18 Blatt, mit 6 Photographien und einem Anhang: Rezensionen von "Autorität und Familie" und "Abstracts" von Aufsätzen aus der Zeitschrift für Sozialforschung, Photokopien, 12 Blatt; "Über Geschichte, Organisation und Tätigkeiten des Instituts für Sozialforschung. Aus einem Bericht" (1943), Teilstück, Typoskript mit handschriftlichen Korrekturen, 10 Blatt; "Annual Report on the Activities of the Social Studies Association, Inc." (6.5.1944), Typoskript, 6 Blatt; "Ten Years on Morningside Hights. A Report on the Institute's History 1934 to 1944 (Dezember 1944): 1. Report, a) als Typoskript vervielfältigt, 36 Blatt, b) Typoskript, 48 Blatt, c) Entwurf des Teils "Philosophical Studies", Typoskript, 4 Blatt; 2. "Letters Regarding Ten Years Report", 1 Blatt; 3. Liste der Empfänger des Reports. 1 Blatt; 4. Max Horkheimer: 1 Brief an Nicholas Murray Butler, New York, 17.4.1945 , 1 Blatt; 5. Briefentwürfe zur Versendung des Reports, 2 Blatt; Theodore Abel: "Evaluation of the Institute's Work" (1944?): 1. Würdigung, Typoskript, englisch, 4 Blatt; 2. Theodore Abel: 1 Brief mit Unterschrift an Leo Löwenthal, New York, 6.3.1946; 3. Abschrift von 1. und 2., Typoskript, 5 Blatt; Über Organisation und Tätigkeiten des Instituts für Sozialforschung (Mai 1945), Typoskript, 3 Blatt;