Kidney-imaging agent comprising recombinant gelatin
An object of the present invention is to provide a kidney-imaging agent which is composed of bioabsorbable materials, transiently accumulates in a kidney for a short period of time, and does not remain in the kidney for a prolonged time after accumulation. The present invention provides a kidney-imaging agent which comprises a gelatin-like protein.
1. A method for imaging, specifically, a kidney affected with a disease, which comprises:
administering, to a subject, a kidney-imaging agent, to thereby deliver the kidney-imaging agent specifically to the kidney affected with the disease, wherein said kidney-imaging agent is a recombinant gelatin labeled with a probe, wherein the recombinant gelatin is not crosslinked, and said kidney imaging agent is dissolved in a liquid, and
imaging the kidney by means of the labeled probe,
wherein the recombinant gelatin has the following (1) or (2):
(1) the amino acid sequence shown in SEQ ID NO: 1; or
(2) an amino acid sequence having 80% or more homology to the amino acid sequence shown in SEQ ID NO: 1 and having an action to accumulate in kidney,
and wherein the disease is acute nephritis, interstitial nephritis, glomerulonephritis, IgA nephropathy, or renal failure by ischemia-reperfusion.
2. The method of claim 1 , wherein the recombinant gelatin comprises repeats of a sequence represented by Gly-X-Y characteristic to collagen and has a molecular weight of 2 KDa to 100 KDa, wherein X and Y each independently represents an amino acid and the plurality of Gly-X-Y sequences may be the same or different.
3. The method of claim 1 , wherein the recombinant gelatin comprises repeats of a sequence represented by Gly-X-Y characteristic to collagen and has a molecular weight of 10 KDa to 90 KDa, wherein X and Y each independently represents an amino acid and the plurality of Gly-X-Y sequences may be the same or different.
4. The method of claim 1 , wherein the recombinant gelatin comprises repeats of a sequence represented by Gly-X-Y characteristic to collagen and has two or more sequences of a cell adhesion signal in a single molecule, wherein X and Y each independently represents an amino acid and the plurality of Gly-X-Y sequences may be the same or different, and wherein the cell adhesion signal sequence is an amino acid sequence represented by Arg-Gly-Asp.
5. The method of claim 1 , wherein the amino acid sequence of the recombinant gelatin does not comprise any of serine and threonine.
6. The method of claim 1 , wherein the amino acid sequence of the recombinant gelatin does not comprise an amino acid sequence represented by Asp-Arg-Gly-Asp (SEQ ID NO: 2).
7. The method of claim 1 , wherein the recombinant gelatin is represented by the following formula:
A-[(Gly-X-Y) n ] m —B
wherein A represents any amino acid or amino acid sequence, B represents any amino acid or amino acid sequence, there exist n amino acids each independently represented by X, there exist n amino acids each independently represented by Y, n represents an integer from 3 to 100, m represents an integer of 2 to 10, X and Y each independently represents an amino acid, and n Gly-X-Y sequences may be the same or different.
8. The method of claim 1 , wherein the recombinant gelatin is represented by the following formula:
Gly-Ala-Pro-[(Gly-X-Y) 63 ] 3 -Gly
wherein there exist 63 amino acids each independently represented by X, there exist 63 amino acids each independently represented by Y, X and Y independently represents an amino acid, and 63 Gly-X-Y sequences may be the same or different.
9. The method of claim 1 , wherein the labeled probe is a fluorescent dye, a radioisotope, a nuclide used for PET, a nuclide used for SPECT, an MRI contrast medium, a CT contrast medium, or a magnetic material.
10. The method of claim 9 , wherein the fluorescent dye is a quantum dot, indocyanine green, or a near-infrared fluorescent dye; each of the radioisotope, the nuclide used for PET, and the nuclide used for SPECT is 11 C, 13 N, 15 O, 18 F, 66 Ga, 67 Ga, 68 Ga, 60 Cu, 61 Cu, 62 Cu, 67 Cu, 64 CU, 48 V, Tc-99m, 241 Am, 55 Co, 57 Co, 153 Gd, 111 In, 133 Ba, 82 Rb, 139 Ce, Te-123m, 137 Cs, 86 Y, 90 Y, 185/187 Re, 186/188 Re, 125 I, or a complex thereof, or a combination thereof; and each of the MRI contrast medium, the CT contrast medium, and the magnetic material is gadolinium, Gd-DTPA, Gd-DTPA-BMA, Gd-HP-DO3A, iodine, iron, iron oxide, chromium, manganese, a complex or chelate complex thereof, or a combination thereof.
11. The method of claim 1 , wherein the recombinant gelatin and the labeled probe are physically or chemically bound directly or via a linker.
12. The method of claim 11 , wherein the bond is a coordinate bond, a covalent bond, a hydrogen bond, a hydrophobic interaction or a physical adsorption.