Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β--emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate

In recent years, implementation of 68Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of 44Sc (half-life = 3.97 h, average β+ energy [Eβ+av] = 632 keV) as a valuable alternative to 68Ga (half-life = 68 min, Eβ+av = 830 keV) for imaging and dosimetry before 177Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotron-produced 44Sc and its in vitro and in vivo comparison with the 177Lu-labeled pendant. Methods: 44Sc was produced via the 44Ca(p,n)44Sc nuclear reaction at a cyclotron (17.6 ± 1.8 MeV, 50 μA, 30 min) using an enriched 44Ca target (10 mg 44CaCO3, 97.00%). Separation from the target material was performed by a semiautomated process using extraction chromatography and cation exchange chromatography. Radiolabeling of a DOTA-folate conjugate (cm09) was performed at 95°C within 10 min. The stability of 44Sc-cm09 was tested in human plasma. 44Sc-cm09 was investigated in vitro using folate receptor–positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice Results: Under the given irradiation conditions, 44Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (>99%). Semiautomated isolation of 44Sc from 44Ca targets allowed formulation of up to 300 MBq of 44Sc in a volume of 200–400 μL of ammonium acetate/HCl solution (1 M, pH 3.5–4.0) within 10 min. Radiolabeling of cm09 was achieved with a radiochemical yield of greater than 96% at a specific activity of 5.2 MBq/nmol. In vitro, 44Sc-cm09 was stable in human plasma over the whole time of investigation and showed folate receptor–specific binding to KB tumor cells. PET/CT images of mice injected with 44Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with 44Sc and 177Lu revealed almost identical pharmacokinetics. Conclusion: This study presents a high-yield production and efficient separation method of 44Sc at a quality suitable for radiolabeling of DOTA-functionalized biomolecules. An in vivo proof-of-concept study using a DOTA-folate conjugate demonstrated the excellent features of 44Sc for PET imaging. Thus, 44Sc is a valid alternative to 68Ga for imaging and dosimetry before 177Lu-radionuclide tumor therapy.

Keeping Promises : Implementing the UNESCO Convention on Cultural Diversity into EU's Internal Policies

Irrespective of the diverse stances taken on the UNESCO Convention’s bearing in the external relations context, since its wording is fairly open-ended, it is clear to all observers that the Convention’s impact will largely depend on how it is implemented. The discussion on the domestic implementation of the Convention, both in the political and in the academic discourses, is only just emerging. The implementation model of the EU and its Member States could set an important example for the international community and for the other State Parties that ratified the UNESCO Convention, as the EU and the Member States acting individually, played a critical role in the approval of the Convention, and in the longer process of promoting cultural concerns on the international scene. Against this background, it is the objective of the present article to analyse in how far EU’s internal policies are taking account of the spirit and letter of the UNESCO Convention on Cultural Diversity, to critically assess these policies and make some recommendations for adjustment.

Promises and hurdles in EU-Kazakhstan energy cooperation. EUCAM Commentary No. 20, November 2011

Kazakhstan’s Prime Minister, Karim Massimov, once referred to energy cooperation as the ‘core’ of relations between his country and the European Union (EU). Indeed, there is great mutual interest in this area. Six percent of the EU’s crude oil imports and 16 percent of its uranium imports come from Kazakhstan. And around 80 percent of the latter’s oil exports go towards Europe. For Kazakhstani producers, access to European lucrative and reliable markets is of utmost importance. Over the last several years, the thrust of Kazakhstan’s foreign policy was aimed at increasing the capacity of the Caspian Pipeline Consortium (CPC) that pumps Kazakhstani oil to Europe. Moreover, Kazmunaigaz’s (KMG) – the national oil and gas company – major external investment was in the Romanian oil company Rompetrol.

The Energy Performance of Buildings: Promises Still Unfulfilled. Egmont Paper No. 78, May 2015

EXECUTIVE SUMMARY All observers agree that energy efficiency must be the cornerstone of any serious EU energy strategy. In this general context, the EU building sector is critical. It represents about 40% of EU final energy consumption (residential houses, public/private offices, commercial buildings, etc.) and approximately 36% of EU CO2 emissions. This is massive. The EU has certainly not been inactive in this field. The Energy Performance in Buildings Directive 2002/91/EC (EPBD) was the first and the main instrument to address the problem of the energy performance of buildings. It has established numerous principles: a reliable methodology which enables the calculation and rating of the energy performance of buildings; minimum energy performance standards for new buildings and existing buildings under major renovation; energy performance certificates; regular inspection of heating and air-conditioning systems; and, finally, quality standards for inspections and energy performance certificates. They were strengthened in 2010 by the recast Directive 2010/31/EU. This directive also introduces a decisive concept for the development of the building sector: ‘nearly zeroenergy buildings’. In 2012, the new Energy Efficiency Directive 2012/27/EU dealt with other aspects. In the building sector, three of them are particularly important. They concern: (1) the establishment of long-term strategies for mobilizing investment in the renovation of the national building stocks; (2) the introduction of energy saving schemes for ‘designated’ energy companies with a view to reducing consumption among ‘final consumers’ by 1.5% annually; and (3), as an option, the setting up of an Energy Efficiency National Fund to support energy efficiency initiatives. This paper also briefly examines the different instruments put in place to disseminate information and consultation, and the EU funding for energy efficiency in buildings. Results, however, have remained limited until now. The improvement of the energy performance of buildings and the rhythm of renovation remain extremely weak. Member States’ unwillingness to timely and properly transpose and implement the Directives continues despite the high degree of flexibility permitted. The decentralized approach chosen for some specific aspects and the differentiation in the application of EPBD standards between Member States do not appear optimal either. Adequate financial schemes remain rare. The permanent deficit of qualified and trained personnel and the inertia of public authorities to make the public understand the stakes in this domain remain problematic. Hence the need to take new initiatives to reap the benefits that the building sector is meant to bring.

Empty promises : the myth of college access in America.

"June 2002."

The youth's guide in Zion ; and Holy Mother's promises /

Appendix: p. [1] at end.

The criminalization of domestic violence : promises and limits /

"January 1996."

Pharmaceutical innovation--promises and problems [microform] : hearing before the Subcommittee on Natural Resources, Agriculture Research, and Environment and the Subcommittee on Investigations and Oversight of the Committee on Science and Technology, U.S. House of Representatives, Ninety-seventh Congress, first session, April 27, 1981.

"No. 145."