1. A computed tomography apparatus for imaging an object, the computed tomography apparatus comprising:
an imaging region for receiving the object to be imaged,
a radiation source for generating modulated radiation traversing the object in the imaging region,
a detector for generating detection values depending on the radiation after having traversed the object,
a moving unit for moving the radiation source and the object relative to each other, while generating the detection values, for generating detection values depending on radiation having traversed the object in different directions,
a weight providing unit for providing modulation weights for weighting the detection values depending on the modulation of the radiation,
a reconstruction unit for reconstructing an image of the object, wherein the reconstruction unit is adapted to weight the detection values based on the provided modulation weights and to reconstruct the image of the object from the weighted detection values.
2. The computed tomography apparatus as defined in claim 1, wherein the computed tomography apparatus comprises an object table on which the object is to be located, wherein the moving unit is adapted to rotate the radiation source around the object table and wherein the radiation source is adapted such that the intensity of the radiation is lower above the object table than below the object table.
3. The computed tomography apparatus as defined in claim 1, wherein the weight providing unit is adapted to determine a noise variance of a detection value and to provide the modulation weight for the detection value depending on the inverse noise variance.
4. The computed tomography apparatus as defined in claim 1, wherein the radiation source is adapted to modulate the intensity of the generated radiation, wherein the weight providing unit is adapted to determine a modulation weight for a detection value depending on the modulated intensity of the generated radiation.
5. The computed tomography apparatus as defined in claim 1, wherein the radiation source is adapted to generate the modulated radiation such that the modulated radiation is conical and wherein the weight providing unit is further adapted to provide coneweights for weighting the detection values depending on a cone angle of the radiation on which the respective detection values depend.
6. The computed tomography apparatus as defined in claim 1, wherein the radiation source is adapted to generate the modulated radiation such that the modulated radiation is divergent, wherein the computed tomography apparatus further comprises a rebinning unit for rebinning the detection values being generated depending on the divergent radiation thereby forming rebinned projections, wherein the weight providing unit is adapted to:
determine intermediate modulation weights for at least a part of the detection values of a rebinned projection, wherein the intermediate modulation weights depend on the modulation of the radiation,
determine for the rebinned projection a mean modulation weight being an average of the intermediate modulation weights for the at least a part of the rebinned detection values of the rebinned projection, wherein the mean modulation weight is the provided modulation weight for the detection values of the rebinned projection.
7. The computed tomography apparatus as defined in claim 6, wherein the moving unit is adapted to rotate the radiation source and the imaging region relative to each other around a rotational axis, while generating the detection values, wherein the at least a part of the rebinned detection values of the rebinned projection are rebinned detection values arranged along a line being perpendicular to the rotational axis.
8. The computed tomography apparatus as defined in claim 6, wherein the computed tomography apparatus further comprises a region of interest selection unit for selecting a region of interest to be reconstructed, wherein the at least a part of the rebinned detection values is a part of the rebinned detection values which has been generated depending on radiation having traversed the selected region of interest.
9. The computed tomography apparatus as defined in claim 6, wherein the weight providing unit is further adapted to determine the mean modulation weight by weightedly averaging the intermediate modulation weights for the at least a part of the rebinned detection values, wherein the intermediate modulation weights are weighted during averaging such that intermediate modulation weights of rebinned detection values which depend on radiation having traversed the region of interest more centrally receive a larger weight than intermediate modulation weights of rebinned detection values which depend on radiation having traversed the region of interest more peripherally.
10. The computed tomography apparatus as defined in claim 8, wherein the weight providing unit is further adapted to determine the mean modulation weight by weightedly averaging the intermediate modulation weights of the at least a part of the rebinned detection values, wherein the intermediate modulation weights are weighted during averaging depending on the size of an intersection region of the region of interest and the radiation on which the respective rebinned detection value depends.
11. An imaging apparatus for generating an image of an object, the imaging apparatus being adapted to process detection values generated by an acquisition unit comprising:
an imaging region for receiving the object to be imaged,
a radiation source for generating modulated radiation traversing the object in the imaging region,
a detector for generating detection values depending on the radiation after having traversed the object,
a moving unit for moving the radiation source and the object relative to each other, while generating the detection values, for generating detection values depending on radiation having traversed the object in different directions, wherein the imaging apparatus comprises:
a weight providing unit for providing modulation weights for weighting the detection values depending on the modulation of the radiation,
a reconstruction unit for reconstructing an image of the object, wherein the reconstruction unit is adapted to weight the detection values based on the provided modulation weights and to reconstruct the image of the object from the weighted detection values.
12. A computed tomography method for imaging an object, the computed tomography method comprising following steps:
generating modulated radiation traversing an object in an imaging region by a radiation source,
generating detection values depending on the radiation after having traversed the object by a detector,
moving the radiation source and the object relative to each other, while generating the detection values, for generating detection values depending on radiation having traversed the object in different directions by a moving unit,
providing weights for the detection values depending on the modulation of the radiation by a weight providing unit,
weighting the detection values based on the provided modulation weights by a reconstruction unit,
reconstructing an image of the object from the weight detection values by the reconstruction unit.
13. An imaging method for generating an image of an object, the imaging method being adapted to process detection values generated by an acquisition unit comprising:
an imaging region for receiving the object to be imaged,
a radiation source for generating modulated radiation traversing the object in the imaging region,
a detector for generating detection values depending on the radiation after having traversed the object,
a moving unit for moving the radiation source and the object relative to each other, while generating the detection values, for generating detection values depending on radiation having traversed the object in different directions, wherein the imaging method comprises following steps:
providing weights for the detection values depending on the modulation of the radiation by a weight providing unit,
weighting the detection values based on the provided modulation weights by a reconstruction unit,
reconstructing an image of the object from the weight detection values by the reconstruction unit.
14. A computed tomography computer program, the computed tomography computer program comprising program code means for causing a computed tomography apparatus as defined in claim 1 to carry out the steps of the computed tomography method, when the computed tomography computer program is run on a computer controlling the computed tomography apparatus.
15. An imaging computer program, the imaging computer program comprising program code means for causing an imaging apparatus as defined in claim 11 to carry out the steps of the imaging method, when the imaging computer program is run on a computer controlling the imaging apparatus.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for determining whether a compound of unknown integrin activity is a competitive ligand of an integrin molecule comprising exposing said integrin molecule to a compound of unknown integrin activity detection of the integrin ligand binding affinity of a compound of unknown integrin activity, allowing a sufficient time for said compound to bind to said integrin and expose at least one ligand induced epitope if said compound is a ligand of said integrin; exposing said integrin molecule to an antibody comprising a reporter which is specific for said ligand induced epitope and determining whether said compound is a ligand of said integrin by measuring the concentration of antibody bound to said integrin and comparing it to at least one control measurement.
2. The method according to claim 1 wherein said control measurement is a measurement of the specific binding of said antibody to said integrin in the presence of a known integrin ligand.
3. The method according to claim 1 wherein said control measurement is a measure of the non-specific binding of said antibody to said integrin in the absence of ligand.
4. The method according to claim 1 wherein said integrin is expressed on a wild-type cell.
5. The method according to claim 1 wherein said integrin is expressed on an engineered cell.
6. The method according to claim 1 wherein said cell expresses more than one integrin.
7. The method according to claim 1 wherein said integrin is expressed on a cell selected from the group consisting of human peripheral blood granulocytes, monocytes, lymphocytes and human platelet cells.
8. The method according to claim 1 wherein said integrin is expressed on a cell selected from the group consisting of U937 cells, MOLT-4 cells, Jurkat cells, THP-1 cells, HL-60 cells, JY cells and MEG-01 cells.
9. The method according to any of claim 1 wherein said integrin is Beta1 integrin (CD29), Beta2 integrin (CD18), AlphaM integrin (CD11b), Beta2 integrin (CD11a), Beta3 integrin (CD61), gpilla (a common subunit for alphaIIb and alphaV integrins), AlphaIIb beta3 integrin, CD41CD61, glycoprotein.IIbIIa (gpIIbIIa) or \u03b14\u03b21 integrin (CD49dCD29).
10. The method according to claim 1 wherein said integrin is \u03b14\u03b21 integrin (CD49dCD29).
11. The method according to claim 1 wherein said antibody is a monoclonal antibody (mAb).
12. The method according to claim 11 wherein said mAb is selected from the group consisting of B44, HUTS-4, HUTS-21, AG89, 9EG7, MEM-148, MEM-48, KIM185, 127, CBRM15, MEM-83; CRC54 and PAC-1.
13. The method according to claim 1 wherein said integrin is said integrin is \u03b14\u03b21 integrin (CD49dCD29) and said antibody is monoclonal antibody HUTS-21 comprising a fluorophore reporter.
14. The method according to claim 1 wherein said reporter is a fluorophore.
15. The method according to claim 14 wherein said fluorophore is selected from the group consisting of fluorescein, isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde label, fluorescamine, tetramethylrhodamine, dipyrrometheneboron difluoride dyes (available from Molecular Probes, Inc, among others), near infrared dyes and lanthanide chelates.
16. The method according to claim 14 wherein said fluorophore is fluorescein or phycoerythrin.
17. The method according to claim 16 wherein said fluorophore is phycoerythrin.
18. The method according to claim 2 wherein said method is adapted for use in flow cytometry.
19. The method according to claim 2 wherein said known ligand is selected from any of compounds set forth in FIG. 1 or an enantiomer thereof.
20. The method according to claim 1 wherein said method is adapted for use in high throughput flow cytometry.
21. The method according to claim 1 wherein said compound, identified as a competitive ligand, is subjected to a further assay to determine whether the compound is an agonist or antagonist of integrin.
22. A method for determining whether or not a compound of unknown integrin activity is an allosteric inhibitor of an integrin molecule comprising exposing said integrin molecule to a known competitive ligand of said integrin molecule in the presence of a integrin-epitope binding antibody comprising a reporter moiety, measuring the binding of said antibody to the integrin molecule in the presence of the competitive ligand; thereafter exposing said bound integrin molecule in the presence of known competitive ligand and bound antibody to a compound of unknown activity and measuring the binding of the antibody to the integrin molecule, wherein the decrease in binding of antibody to integrin is evidence that the compound of unknown activity is an allosteric inhibitor of integrin.
23. The method according to claim 22 wherein the decrease in binding of antibody to integrin is compared to a control wherein the control is a measurement of the non-specific binding of the antibody to the integrin molecule.
24. (canceled)
25. (canceled)
26. (canceled)
27. (canceled)
28. (canceled)
29. (canceled)
30. (canceled)
31. (canceled)
32. (canceled)
33. (canceled)
34. (canceled)
35. (canceled)
36. (canceled)
37. (canceled)
38. (canceled)
39. (canceled)
40. (canceled)
41. A pharmaceutical composition comprising an effective amount of a compound according to the chemical structure:
or a pharmaceutically acceptable salt or enantiomer thereof, optionally in combination with a pharmaceutically acceptable carrier, additive or excipient.
42. (canceled)
43. (canceled)
44. (canceled)
45. (canceled)
46. (canceled)
47. A pharmaceutical composition comprising a compound according to the chemical structure I:
Where
R1 is C1-C4 linear or branched alkyl group; and
R2 is an optionally substituted cyclic or bicyclic hydrocarbon or an optionally substituted 5-10 membered heterocyclic ring or fused bicyclic ring system, or
a pharmaceutically acceptable salt, enantiomer, solvate or polymorph thereof, optionally in combination with a pharmaceutically acceptable carrier, additive or excipient.
48. The pharmaceutical composition according to claim 47 wherein said compound has the chemical structure:
49. The composition according to claim 47 wherein R2 is an adamantly group.
50-56. (canceled)