High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment

Rapid imaging by antitumor antibodies has been limited by the prolonged targeting kinetics and clearance of labeled whole antibodies. Genetically engineered fragments with rapid access and high retention in tumor tissue combined with rapid blood clearance are suitable for labeling with short-lived radionuclides, including positron-emitting isotopes for positron-emission tomography (PET). An engineered fragment was developed from the high-affinity anticarcinoembryonic antigen (CEA) monoclonal antibody T84.66. This single-chain variable fragment (Fv)-CH3, or minibody, was produced as a bivalent 80 kDa dimer. The macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N,N′,N′′, N′′′-tetraacetic acid (DOTA) was conjugated to the anti-CEA minibody for labeling with copper-64, a positron-emitting radionuclide (t1/2 = 12.7 h). In vivo distribution was evaluated in athymic mice bearing paired LS174T human colon carcinoma (CEA positive) and C6 rat glioma (CEA negative) xenografts. Five hours after injection with 64Cu-DOTA-minibody, microPET imaging showed high uptake in CEA-positive tumor (17.9% injected dose per gram ± 3.79) compared with control tumor (6.0% injected dose per gram ± 1.0). In addition, significant uptake was seen in liver, with low uptake in other tissues. Average target/background ratios relative to neighboring tissue were 3–4:1. Engineered antibody fragments labeled with positron-emitting isotopes such as copper-64 provide a new class of agents for PET imaging of tumors.

Tunisia. Supervising Tunisian Elections by civil society: How to improve it? Arab Citizenship Review No. 7. January 2015

Introduction. On October 26, 2014, Tunisia held its second democratic legislative elections. Participation among more than 5 million registered voters was at about 60%, a relatively good turnout for the country, compared to the 52% voters in 2011. Preliminary results for the 33 constituencies (27 within the country and 6 for expatriates) reveal that secular frontrunner Nidaa Tounes (Call of Tunisia) won around 37% percent of votes while moderate Islamist party Ennahdha, winner of the 2011 elections and leader of Tunisia’s post-revolution government, received 27% of votes. Other parties with notable percentages are the Free Patriotic Union (French: UPL) with 4.4% and the leftist party, Popular Front, with 3.7%. Legislative were immediately followed by two round presidential elections the first one held on November 23, the second one after one month. Conversely to what was expected, people were more attracted by presidential elections even though president has notably less prerogatives than the parliament: representing the state, he is mainly responsible for determining the general state policies in the domains of defense, foreign relations and national security (article 76.) This paradox is ascribed to national imaginary more confident in a “Zaïm” (leader) rather than a collective institution such as a parliament. The turnout was at about 64% within the national 27 constituencies. Out of 70 candidates (including 5 female), 27 (with only one female) met the legal requirements to run for the presidency. The result confirms the legislative trend and Beji Caid Essebsi, leader of Nidaa, was proclaimed the third President of Tunisia. He gained 39.46% of the votes at the first round elections. Essebsi was followed by Moncef Marzouki who received an unexpected score (33.43%) at the first round, thanks to the support of Ennahdha audience and to an active and insistent campaign focused on the idea that revolution is threatened by old regime guard “come-back.” Rewarded for his long militant live, the extreme leftist Hamma Hammami in a new look gained 7,8% of the votes while the new comer Slim Riahi received 5,5% despite rumors circulating on his personal reputation. Notably, Kalthoum Kennou gained 0,55% (18.287 votes) but listed eleventh out of 27.