Very Late Antigen-4 (α<inf>4</inf>β<inf>1</inf> Integrin) Targeted PET Imaging of Multiple Myeloma

Biomedical imaging techniques such as skeletal survey and 18F-fluorodeoxyglucose (FDG)/Positron Emission Tomography (PET) are frequently used to diagnose and stage multiple myeloma (MM) patients. However, skeletal survey has limited sensitivity as it can detect osteolytic lesions only after 30-50% cortical bone destruction, and FDG is a marker of cell metabolism that has limited sensitivity for intramedullary lesions in MM. Targeted, and non-invasive novel probes are needed to sensitively and selectively image the unique molecular signatures and cellular processes associated with MM. Very late antigen-4 (VLA-4; also called α4β1 integrin) is over-expressed on MM cells, and is one of the key mediators of myeloma cell adhesion to the bone marrow (BM) that promotes MM cell trafficking and drug resistance. Here we describe a proof-of-principle, novel molecular imaging strategy for MM tumors using a VLA-4 targeted PET radiopharmaceutical, 64Cu-CB-TE1A1P-LLP2A. Cell uptake studies in a VLA-4-positive murine MM cell line, 5TGM1, demonstrated receptor specific uptake (P<0.0001, block vs. non-block). Tissue biodistribution at 2 h of 64Cu-CB-TE1A1P-LLP2A in 5TGM1 tumor bearing syngeneic KaLwRij mice demonstrated high radiotracer uptake in the tumor (12±4.5%ID/g), and in the VLA-4 rich organs, spleen (8.8±1.0%ID/g) and marrow (11.6±2.0%ID/g). Small animal PET/CT imaging with 64Cu-CB-TE1A1P-LLP2A demonstrated high uptake in the 5TGM1 tumors (SUV 6.6±1.1). There was a 3-fold reduction in the in vivo tumor uptake in the presence of blocking agent (2.3±0.4). Additionally, 64Cu-CB-TE1A1P-LLP2A demonstrated high binding to the human MM cell line RPMI-8226 that was significantly reduced in the presence of the cold targeting agent. These results provide pre-clinical evidence that VLA-4-targeted imaging using 64Cu-CB-TE1A1P-LLP2A is a novel approach to imaging MM tumors. © 2013 Soodgupta et al

Thoracic endograft positioning and carotid-subclavian bypass grafting in a patient with a saccular aneurysm at the aortic arch

A 75-year-old man was referred to our hospital because of sudden thoracic pain. A saccular aneurysm of the aortic arch extending on the anterior surface of the aortic arch was found on computed tomographic arteriography. The patient was hemodynamically stable and he was programmed for a staged surgical and endovascular approach (hybrid approach),. As a first stage and in order to prevent major cardiac complications due to the overstenting of the left subclavian artery (LSA) with the occlusion of the aortocoronary bypass, the patient underwent a polytetrafluoroethylene bypass graft (GORE-TEX, W.L. Gore & Associates, Flagstaff, AZ) between the LSA and the left carotid artery. Intraoperative arteriography revealed a good patency of the left carotid-subclavian bypass and of the left internal mammary bypass on the left anterior descending artery. As a second stage the endovascular procedure was accomplished 5 days later in the operating room. A Gore TAG stent graft (W.L. Gore & Associates) was deployed in the aortic arch 20 mm proximally to the aneurysmatic segment covering the ostium of the LSA. The postoperative course was uneventful and the patient was discharged on the fifth postoperative day in good general conditions. Hybrid procedures for treatment of aneurysms of the aortic arch or of the descending thoracic aorta are a promising alternative to open surgery especially in high-risk patients, with lower early morbidity and mortality rates. Long-term effectiveness remains to be fully elucidated

Integrated Close Range Remote Sensing Techniques for Detecting, Documenting, and Interpreting Lost Medieval Settlements under Canopy: The Case of Altanum (RC, Italy)

This paper focuses on the potential of an integrated approach using aerial LiDAR, aerial and terrestrial photogrammetry, terrestrial laser scanning, and archaeological survey to detect the presence and configuration of lost medieval settlements under canopy. This approach was applied to the site of Altanum (Calabria, Italy), on the hill of Sant'Eusebio, completely covered by vegetation. Altanum was a large fortified settlement characterised by a long occupation, especially during the Byzantine and Norman-Swabian periods. The activity began by carrying out a LiDAR survey of the whole hill. The acquired LiDAR data were processed and filtered in order to obtain a DFM (Digital Feature Model) useful for the identification of features of archaeological interest. Several enhancement techniques were performed on DFM to increase the visibility of archaeological features. The features thus identified were subsequently surveyed through the use of terrestrial and aerial photogrammetry integrated with laser scanning to document the visible buildings. The most significant result of the study was to create a single GIS platform with the integration of all data in order to delineate the whole settlement layout, as well as to produce 2D and 3D datasets useful for the for knowledge and protection of the identified remains

Continuous low temperature synthesis of MAPbX<inf>3</inf> perovskite nanocrystals in a flow reactor

Perovskite nanocrystals prepared at room temperature using a simple flow reactor.</p

Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide

Significant upregulation of the integrin α v β 6 has been described as a prognostic indicator in several cancers, making it an attractive target for tumor imaging. This study compares variants of a PEGylated α v β 6 -targeting peptide, bearing either an [>18F]fluorobenzoyl prosthetic group ([ 18 F]FBA-PEG-A20FMDV2) or different [ 64 Cu]copper chelators (DOTA-PEG-A20FMDV2, CB-TE2A-PEG-A20FMDV2). The compounds were evaluated in vitro by enzyme-linked immunosorbent assay (against the integrin α v β 6 and the closely related integrin α v β 6 ) and by cell labeling (α v β 6 -positive DX3puroβ6/α v β 6 -negative DX3puro) and in vivo using micro-positron emission tomography in a mouse model bearing paired DX3puroβ6/Dx3puro xenografts. In vitro, all three compounds showed excellent α v β 6 -specific binding (50% inhibitory concentration [IC 50 ](α v β 6 ) = 3 to g nmol/L; IC 50 (α v β 3 ) > 10 (μmol/L). In vivo, they displayed comparable, preferential uptake for the α v β 6 -expressmg xenograft over the α v β 6 -negative control (> 4:1 ratio at 4 hours postinjection). Whereas [ 64 Cu]Cu-DOTA-PEG-A20FMDV2 resulted in increased levels of radioactivity in the liver, [ 64 Cu]Cu-CB-TE2A-PEG-A20FMDV2 did not. Significantly, both 64 Cu-labeled tracers showed unexpectedly high and persistent levels of radioactivity in the kidneys (> 40% injected dose/g at 4 and 12 hours postinjection). The findings underscore the potential influence of the prosthetic group on targeted in vivo imaging of clinically relevant markers such as α v β 6 . Despite identical targeting peptide moiety and largely equal in vitro behavior, both 64 Cu-labeled tracers displayed inferior pharmacokinetics, making them in their present form less suitable candidates than the 18 F-labeled tracer for in vivo imaging of α v β