Abstract: A method for preparing a suspension of size-controlled microparticles stabilized by a layer of amphiphilic material. The method, which may be applied to preparations using microfluidic techniques, comprises controlling the temperature of the microparticles during the preparation process and preferably while collecting the formed microparticles.

Abstract: The invention discloses a recombinant protein (P-selectin glycoprotein ligand-1 and Neural Retina-specific Leucine Zipper) PSGL-1-NRL chimeric protein comprising a Selectin Binding domain and a non-covalent dimerization domain, which is a leucine zipper and is more preferably the leucine zipper domain of the human or mouse Neural Retina-specific Leucine Zipper. The chimeric protein further comprises a covalent dimerization domain with at least one cysteine suitable to form a disulfide bridge with another chimeric protein to form a homodimer. In the chimeric protein, the PSGL-1 domain corresponds to the extracellular region of Human PSGL-1 and is more preferably the selectin binding region of the mature protein. The chimeric protein is correctly post-translationally modified and is efficiently expressed in a mammalian system. It is sulfated, O-linked glycosylated and sialylated and binds P, E and L selectin, allowing in vivo and in vitro targeting for diagnostic or therapeutic purposes.

Abstract: The present invention relates to a new composition comprising gas-filled microvesicles for contrast imaging which are particularly suitable for providing an effective echo response to at least two selected ultrasound waves having different frequencies. Said composition preferably comprises at least two different preparations of gas-filled microvesicles having respective peaks of non-linear echographic response differing by at least 2 MHz to each other, and preferably have respective size distributions with different median sizes. In particular, said preparations preferably have size distributions with respective DV50 values differing from each other by at least 0.5 ?m, more preferably at least 1.0 ?m. Alternatively, said composition has a volume size distribution showing a value of Bowley skewness of 0.16 or higher.

Abstract: A formulation for preparing gas-filled microvesicles which comprises a phospholipid and a mixture of saturated and unsaturated fatty acids. The gas-filled microvesicles having a stabilizing layer comprising said composition show an increased stability with respect to microvesicles containing only a saturated or an unsaturated fatty acid.

Abstract: Suspension of gas-filled microvesicles comprising a targeting ligand for binding to KDR or VEGF/KDR complex. The suspension is obtained by reconstituting a freeze-dried residue with a carbohydrate-containing solution in the presence of a physiologically acceptable gas and is stabilized by the presence of histidine.

Abstract: Gas-filled microvesicles comprising an antigen bound thereto and to aqueous suspensions containing said microvesicles, for use in immunomodulating formulations, in particular as a vaccine. The antigen is covalently bound to a component of the microvesicles envelope. The microvesicles of the invention, comprising a molar excess of fatty acids in the stabilizing envelope, are particularly effective in the uptake by antigen-presenting cells, in particular dendritic cells.

Abstract: Gas-filled microvesicles comprising an antigen bound thereto and to aqueous suspensions containing said microvesicles, for use in immunomodulating formulations, in particular as a vaccine. The antigen is covalently bound to a component of the microvesicles envelope. The microvesicles of the invention are particularly effective in the uptake by antigen-presenting cells, in particular dendritic cells.

Abstract: Assembly comprising a gas-filled microvesicle and a structural entity which is capable to associate through an electrostatic interaction to the outer surface of said microvesicle (microvesicle associated component—MAC), thereby modifying the physico-chemical properties thereof. Said MAC may optionally comprise a targeting ligand, a bioactive agent, a diagnostic agent or any combination thereof. The assembly of the invention can be formed from gasfilled microbubbles or microballoons and a MAC having a diameter of less than 100 pm, in particular a micelle and is used as an active component in diagnostically and/or therapeutically active formulations, in particular for enhancing the imaging in the field of ultrasound contrast imaging, including targeted ultrasound imaging, ultrasound-mediated drug delivery and other imaging techniques such as molecular resonance imaging (MRI) or nuclear imaging.

Abstract: The present invention provides polypeptides, peptide dimer, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD<1 ?M), and dimer and multimeric constructs comprising these polypeptides.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: The present invention provides polypeptides, peptide dimers, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD<1 ?M), and dimer and multimeric constructs comprising these polypeptides, particularly contrast agents. Also provided are methods for monitoring and evaluating the therapeutic effectiveness of treatment protocols for diseases associated with angiogenesis or endothelial cell hyperproliferation, such as cancer, using contrast agents of the invention.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: The present invention relates to a new composition comprising gas-filled microvesicles for contrast imaging which are particularly suitable for providing an effective echo response to at least two selected ultrasound waves having different frequencies. Said composition preferably comprises at least two different preparations of gas-filled microvesicles having respective peaks of non-linear echographic response differing by at least 2 MHz to each other, and preferably have respective size distributions with different median sizes. In particular, said preparations preferably have size distributions with respective DV50 values differing from each other by at least 0.5 ?m, more preferably at least 1.0 ?m. Alternatively, said composition has a volume size distribution showing a value of Bowley skewness of 0.16 or higher.

Abstract: Method for preparing a lyophilized matrix and, upon reconstitution of the same, a respective injectable contrast agent comprising a liquid aqueous suspension of gas-filled microbubbles stabilized predominantly by a phospholipid. The method comprises preparing an emulsion from an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and subsequently reconstituted in an aqueous suspension of gas-filled microbubbles. The method allows to obtain suspensions comprising microbubbles having a relatively small diameter and a narrow size distribution.

Abstract: Gas-filled microvesicles associated with a polypeptide comprising a sequence of amino acids, said sequence exhibiting binding affinity for selectins, particularly p-selectin. The gas-filled microvesicles can be used in ultrasound imaging.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: Gas-filled microvesicles associated with a polypeptide comprising a sequence of amino acids, said sequence exhibiting binding affinity for selectins, particularly p-selectin. The gas-filled microvesicles can be used in ultrasound imaging.

Abstract: The present invention relates to a new composition comprising gas-filled microvesicles for contrast imaging which are particularly suitable for providing an effective echo response to at least two selected ultrasound waves having different frequencies. Said composition preferably comprises at least two different preparations of gas-filled microvesicles having respective peaks of non-liner echographic response differing by at least 2 MHz to each other, and preferably have respective size distributions with different mean sizes. In particular, said preparations preferably have size distributions with respective DV50 values differing from each other by at least 0.5 ?m, more preferably at least 1.0 ?m. Alternatively, said composition has a volume size distribution showing a value of Bowley skewness of 0.16 or higher.

Abstract: Gas-filled microvesicles associated with a polypeptide comprising a sequence of amino acids, said sequence exhibiting binding affinity for selectins, particularly p-selectin. The gas-filled microvesicles can be used in ultrasound imaging.

Abstract: A formulation for preparing gas-filled microvesicles which comprises a phospholipid and a mixture of saturated and unsaturated fatty acids. The gas-filled microvesicles having a stabilizing layer comprising said composition show an increased stability with respect to microvesicles containing only a saturated or an unsaturated fatty acid.