Compositions and methods for imaging

1. A method of determining the distribution of an immune checkpoint ligand in an individual, comprising:

(a) administering to the individual an imaging agent comprising an antibody moiety labeled with a radionuclide, wherein the antibody moiety specifically binds the immune checkpoint ligand, wherein the antibody moiety comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 41, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO: 42, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO: 43; and a light chain variable region (VL) comprising a light chain complementarity determining region (LC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 44, a LC-CDR2 comprising an amino acid sequence of SEQ ID NO: 45, and a LC-CDR3 comprising an amino acid sequence of SEQ ID NO: 46;

(b) imaging the imaging agent in the individual with a non-invasive imaging technique; and

(c) determining the expression level of the immune checkpoint ligand in a tissue of interest in the individual based on signals emitted by the imaging agent from the tissue.

2. A method of diagnosing an individual having a disease or condition, wherein the disease or condition is associated with an abnormal immune response, comprising:

(a) determining the distribution of an immune checkpoint ligand in the individual by administering to the individual an imaging agent comprising an antibody moiety labeled with a radionuclide, wherein the antibody moiety specifically binds the immune checkpoint ligand, wherein the antibody moiety comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 41, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO: 42, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO: 43; and a light chain variable region (VL) comprising a light chain complementarity determining region (LC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 44, a LC-CDR2 comprising an amino acid sequence of SEQ ID NO: 45, and a LC-CDR3 comprising an amino acid sequence of SEQ ID NO: 46; and imaging the imaging agent in the individual with a non-invasive imaging technique; and

(b) diagnosing the individual as positive for the immune checkpoint ligand if signal of the imaging agent is detected at a tissue of interest, or diagnosing the individual as negative for the immune checkpoint ligand if signal of the imaging agent is not detected at a tissue of interest.

3. A method of treating an individual having a disease or condition, wherein the disease or condition is associated with an abnormal immune response, comprising:

(a) diagnosing the individual using the method of claim 2 ; and

(b) administering to the individual an effective amount of a therapeutic agent targeting the immune checkpoint ligand, if the individual is diagnosed as positive for the immune checkpoint ligand.

4. An isolated anti-PD-L1 antibody agent comprising an antibody moiety comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 41, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO: 42, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO: 43; and a light chain variable region (VL) comprising a light chain complementarity determining region (LC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 44, a LC-CDR2 comprising an amino acid sequence of SEQ ID NO: 45, and a LC-CDR3 comprising an amino acid sequence of SEQ ID NO: 46.

5. The isolated anti-PD-L1 antibody agent of claim 4 , wherein the antibody moiety comprises: a VH comprising an amino acid sequence having at least 80% sequence identity to an amino acid sequence of any one of SEQ ID NOs: 1, 5, 9, 11, and 13; and a VL comprising an amino acid sequence having at least 80% sequence identity to an amino acid sequence of any one of SEQ ID NOs: 3, 7, 15, 17 and 19.

6. The isolated anti-PD-L1 antibody agent of claim 4 , wherein the antibody moiety comprises an scFv.

7. The isolated anti-PD-L1 antibody agent of claim 6 , wherein the scFv comprises a first cysteine residue at position 44 of VH and a second cysteine residue at position 100 of VL, or a first cysteine residue at position 105 of VH and a second cysteine residue at position 43 of VL, wherein the first cysteine residue and the second cysteine residue form a disulfide bond, and wherein the amino acid positions are based on the Kabat numbering system.

8. The isolated anti-PD-L1 antibody agent of claim 6 , wherein the scFv comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 25, 27, 29, 31, 33, 35, 37 and 39.

9. The isolated anti-PD-L1 antibody agent of claim 6 , wherein the antibody moiety is an scFv.

10. The isolated anti-PD-L1 antibody agent of claim 6 , wherein the antibody moiety is an scFv fused to an Fc fragment.

11. The isolated anti-PD-L1 antibody agent of claim 10 , wherein the Fc fragment is a human IgG1 Fc fragment.

12. The isolated anti-PD-L1 antibody agent of claim 11 , wherein the Fc fragment has H310A and H435Q mutations, wherein the amino acid positions are based on the Kabat numbering system.

13. An anti-PD-L1 antibody agent comprising an antibody moiety that specifically binds PD-L1 competitively with the antibody moiety in the anti-PD-L1 antibody agent of claim 4 .

14. An imaging agent comprising an antibody moiety labeled with a radionuclide, wherein the antibody moiety specifically binds an immune checkpoint ligand, and wherein the antibody moiety comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 41, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO: 42, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO: 43; and a light chain variable region (VL) comprising a light chain complementarity determining region (LC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 44, a LC-CDR2 comprising an amino acid sequence of SEQ ID NO: 45, and a LC-CDR3 comprising an amino acid sequence of SEQ ID NO: 46.

15. An imaging agent comprising the isolated anti-PD-L1 antibody agent of claim 4 , wherein the antibody moiety is labeled with a radionuclide.

16. A method of preparing an imaging agent targeting PD-L1, comprising:

(a) conjugating a chelating compound to the antibody moiety in the isolated anti-PD-L1 antibody agent of claim 4 provide an anti-PD-L1 conjugate;

(b) contacting a radionuclide with the anti-PD-L1 antibody conjugate, thereby providing the imaging agent.

17. An isolated nucleic acid encoding the isolated anti-PD-L1 antibody agent of claim 4 .

18. A kit comprising:

(a) an antibody moiety specifically binding an immune checkpoint ligand, wherein the antibody moiety comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 41, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO: 42, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO: 43; and a light chain variable region (VL) comprising a light chain complementarity determining region (LC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 44, a LC-CDR2 comprising an amino acid sequence of SEQ ID NO: 45, and a LC-CDR3 comprising an amino acid sequence of SEQ ID NO: 46; and

(b) a chelating compound.

19. A kit comprising:

(a) an imaging agent comprising an antibody moiety labeled with a radionuclide, wherein the antibody moiety specifically binds an immune checkpoint ligand, wherein the antibody moiety comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 41, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO: 42, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO: 43; and a light chain variable region (VL) comprising a light chain complementarity determining region (LC-CDR)1 comprising an amino acid sequence of SEQ ID NO: 44, a LC-CDR2 comprising an amino acid sequence of SEQ ID NO: 45, and a LC-CDR3 comprising an amino acid sequence of SEQ ID NO: 46; and

(b) an antibody moiety not labeled with a radionuclide.

20. The isolated anti-PD-L1 antibody agent of claim 4 , wherein the antibody moiety comprises:

(a) a VH comprising an amino acid sequence of SEQ ID NO: 1; and a VL comprising an amino acid sequence of SEQ ID NO: 3;

(b) a VH comprising an amino acid sequence of SEQ ID NO: 1; and a VL comprising an amino acid sequence of SEQ ID NO: 7;

(c) a VH comprising an amino acid sequence of SEQ ID NO: 1; and a VL comprising an amino acid sequence of SEQ ID NO: 15;

(d) a VH comprising an amino acid sequence of SEQ ID NO: 1; and a VL comprising an amino acid sequence of SEQ ID NO: 17;

(e) a VH comprising an amino acid sequence of SEQ ID NO: 1; and a VL comprising an amino acid sequence of SEQ ID NO: 19;

(f) a VH comprising an amino acid sequence of SEQ ID NO: 5; and a VL comprising an amino acid sequence of SEQ ID NO: 3;

(g) a VH comprising an amino acid sequence of SEQ ID NO: 5; and a VL comprising an amino acid sequence of SEQ ID NO: 7;

(h) a VH comprising an amino acid sequence of SEQ ID NO: 5; and a VL comprising an amino acid sequence of SEQ ID NO: 15;

(i) a VH comprising an amino acid sequence of SEQ ID NO: 5; and a VL comprising an amino acid sequence of SEQ ID NO: 17;

(j) a VH comprising an amino acid sequence of SEQ ID NO: 5; and a VL comprising an amino acid sequence of SEQ ID NO: 19;

(k) a VH comprising an amino acid sequence of SEQ ID NO: 9; and a VL comprising an amino acid sequence of SEQ ID NO: 3;

(l) a VH comprising an amino acid sequence of SEQ ID NO: 9; and a VL comprising an amino acid sequence of SEQ ID NO: 7;

(m) a VH comprising an amino acid sequence of SEQ ID NO: 9; and a VL comprising an amino acid sequence of SEQ ID NO: 15;

(n) a VH comprising an amino acid sequence of SEQ ID NO: 9; and a VL comprising an amino acid sequence of SEQ ID NO: 17;

(o) a VH comprising an amino acid sequence of SEQ ID NO: 9; and a VL comprising an amino acid sequence of SEQ ID NO: 19;

(p) a VH comprising an amino acid sequence of SEQ ID NO: 11; and a VL comprising an amino acid sequence of SEQ ID NO: 3;

(q) a VH comprising an amino acid sequence of SEQ ID NO: 11; and a VL comprising an amino acid sequence of SEQ ID NO: 7;

(r) a VH comprising an amino acid sequence of SEQ ID NO: 11; and a VL comprising an amino acid sequence of SEQ ID NO: 15;

(s) a VH comprising an amino acid sequence of SEQ ID NO: 11; and a VL comprising an amino acid sequence of SEQ ID NO: 17;

(t) a VH comprising an amino acid sequence of SEQ ID NO: 11; and a VL comprising an amino acid sequence of SEQ ID NO: 19;

(u) a VH comprising an amino acid sequence of SEQ ID NO: 13; and a VL comprising an amino acid sequence of SEQ ID NO: 3;

(v) a VH comprising an amino acid sequence of SEQ ID NO: 13; and a VL comprising an amino acid sequence of SEQ ID NO: 7;

(w) a VH comprising an amino acid sequence of SEQ ID NO: 13; and a VL comprising an amino acid sequence of SEQ ID NO: 15;

(x) a VH comprising an amino acid sequence of SEQ ID NO: 13; and a VL comprising an amino acid sequence of SEQ ID NO: 17; or

(y) a VH comprising an amino acid sequence of SEQ ID NO: 13; and a VL comprising an amino acid sequence of SEQ ID NO: 19.

21. The isolated anti-PD-L1 antibody agent of claim 4 , wherein the antibody moiety comprises: a VH comprising an amino acid sequence of SEQ ID NO: 9; and a VL comprising an amino acid sequence of SEQ ID NO: 17.