# US 12,005,129 B2 · Imaging compositions

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- Number: US 12,005,129 B2
- Document ID: US12005129B2
- Status: Granted
- Kind: B2
- Application number: 16/337,501
- Filed: 2017-10-06
- Published: 2019-09-19
- Granted: 2024-06-11
- Earliest claimed: 2016-10-06
- Assignees: The Penn State Research Foundation
- Applicants: The Penn State Research Foundation
- Inventors: Jian Yang; Dingying Shan; Nanyin Zhang
- Web page: https://patentgrep.com/patent/US12005129B2

## CPC

- A61K 49/126: {Linear polymers, e.g. dextran, inulin, PEG}
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers}
- A61K 49/085: {conjugated systems}
- A61K 49/105: {the metal complex being Gd-DTPA}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

In one aspect, compositions are described herein. In some embodiments, a composition described herein comprises, consists of, or consists essentially of an MRI-active or MRI-sensitive polymer or oligomer formed from (i) a non-alkoxylated and non-alkenoxylated citric acid, citrate, or ester/amide of citric acid, and optionally an alkoxylated or alkenoxylated citric acid, citrate, or ester/amide of citric acid, (ii) a polyol/polyamine such as a diol/diamine, (iii) a monomer comprising an MRI contrast agent, and (iv) an amino acid monomer. The polymer or oligomer may be photoluminescent and MRI-sensitive. In another aspect, imaging methods utilizing the compositions described herein are described. In another aspect, scaffolds, grafts, and films comprising, consisting of, or consisting essentially of the compositions described herein are described.

## Claims

### Claim 1

A composition comprising:
a polymer or oligomer formed from first reacting:
a) one or more monomers of Formula (A1) and optionally one or more monomers of Formula (A2);
b) one or more monomers of Formula (B1) or (B2);
c) one or more monomers of Formula (F);
d) one or more monomers comprising an MRI contrast agent of Formula (J1), (J2), (J3), (J4), (J5), or (J6), and
optionally one or more other reactants or monomers;
such that the polymer or oligomer has the one or more monomers comprising an MRI contrast agent as a part of a backbone of the polymer or oligomer,
wherein the one or more monomers comprising an MRI contrast agent participate in a condensation polymerization reaction to form the polymer or oligomer;
wherein the formed polymer or oligomer is then crosslinked to form a polymer network,
HO-[M]-OH (J1),
HOOC-[M]-COOH (J2),
H2N-[M]-NH2 (J3),
HO-[M]-COOH (J4),
HO-[M]-NH2 (J5),
HOOC-[M]-NH2 (J6),
wherein X1, X2, and X3 are each independently O or NH;
R1, R2, and R3 are each independently H, a C1 to C22 alkyl or alkenyl group, or M+;
R4 is H, a C1 to C22 alkyl or alkenyl group, or M+;
R5 is C(O)R23;
M+ is a monovalent metal cation;
R6 is H, NH2, OH, OCH3, OCH2CH3, CH3, or CH2CH3;
R7 is H or a C1 to C23 alkyl or alkenyl group;
R8 is H, a C3 to C22 alkyl or alkenyl group, CH2CH2OH, or CH2CH2NH2;
R15 is an amino acid side chain;
R23 is a C14 to C22 alkyl or alkenyl group;
[M] is a metal-containing portion of the MRI contrast agent;
wherein n is integer ranging from 2 to 20 and
m is integer ranging from 1 to 20.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the polymer or oligomer is formed by reacting:
a) the one or more monomers of Formula (A1) and optionally the one or more monomers of Formula (A2);
b) the one or more monomers of Formula (B1) or (B2);
c) the one or more monomers of Formula (F);
d) the one or more monomers comprising the MRI contrast agent of Formula (J1), (J2), (J3), (J4), (J5), or (J6);
and
e) one or more monomers of Formula (K):
wherein R24 is H or a C1 to C20 alkyl or alkenyl group; and
r and s are each independently an integer between 0 and 20.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the polymer or oligomer is formed by reacting:
a) the one or more monomers of Formula (A1) and optionally the one or more monomers of Formula (A2);
b) the one or more monomers of Formula (B1) or (B2);
c) the one or more monomers of Formula (F);
d) the one or more monomers comprising the MRI contrast agent of Formula (J1), (J2), (J3), (J4), (J5), or (J6); and
e) one or more monomers of Formula (C), Formula (D1), Formula (D2), Formula (D3), Formula (D4), Formula (E1), Formula (E2), Formula (G), Formula (H1), Formula (H2), Formula (H3), Formula (I1), Formula (I2), Formula (I3), Formula (I4), Formula (I5), and/or Formula (I6):
wherein R9, R10, R11, and R12 are each independently H, OH, CH2(CH2)xNH2, CH2(CHR13)NH2, CH2(CH2)xOH, CH2(CHR13)OH, or CH2(CH2)xCOOH;
R13 is COOH or (CH2)yCOOH;
x is an integer ranging from 0 to 10;
y is an integer ranging from 1 to 10;
p is an integer ranging from 1 to 10;
R14 is OH, OCH3, OCH2CH3, or Cl;
R15 is an amino acid side chain;
q is an integer ranging from 1 to 20;
X5 is O or NH;
R16 is CH3 or CH2CH3,
R17 and R18 are each independently CH2N3, CH3, or CH2CH3,
X6 and Y are each independently O or NH;
R19 and R20 are each independently CH3 or CH2CH3,
R21 is O(CO)C≡CH, CH3, or CH2CH3; and
R22 is CH3, OH or NH2.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the polymer or oligomer is formed from one or more monomers comprising one or more alkyne moieties or one or more azide moieties.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the polymer or oligomer is formed from one or more monomers comprising one or more azide moieties, and the one or more monomers comprising one or more azide moieties comprises a monomer of Formula (HI), (H2), or (H3).

### Claim 6 (depends on 4)

The composition of claim 4, wherein the polymer or oligomer is formed from one or more monomers comprising one or more alkyne moieties, and the one or more monomers comprising one or more alkyne moieties comprises a monomer of Formula (I1), (I2), (B), (I4), (I5), or (I6).

### Claim 7 (depends on 4)

The composition of claim 4, wherein the one or more monomers comprising one or more alkyne moieties or one or more azide moieties comprises a peptide, polypeptide, nucleic acid, or polysaccharide.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the polymer or oligomer is luminescent and MRI-sensitive.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the polymer or oligomer is luminescent in the near-infrared region.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the polymer or oligomer is biodegradable.

### Claim 11 (depends on 1)

A method of imaging a biological environment comprising:
disposing the composition of claim 1 in the biological environment.

### Claim 12 (depends on 11)

The method of claim 11 further comprising:
exposing the biological environment to electromagnetic radiation having a wavelength corresponding to an excitation wavelength of a luminescent moiety of the polymer or oligomer of the composition; and
detecting light emitted by the luminescent moiety.

### Claim 13 (depends on 11)

The method of claim 11, further comprising:
exposing the biological environment to radio-frequency electromagnetic radiation while the biological environment is disposed in a magnetic field, thereby exciting hydrogen atoms of the biological environment; and
detecting relaxation of the excited hydrogen atoms.

### Claim 14 (depends on 1)

A scaffold comprising the composition of claim 1.

### Claim 15 (depends on 1)

A graft comprising the composition of claim 1.

### Claim 16 (depends on 1)

A film comprising the composition of claim 1.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the one or more monomers comprising the MRI contrast agent are bonded to the backbone of the polymer or oligomer through OH and/or COOH moieties.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the one or more monomers comprising the MRI contrast agent are a part of a backbone of the polymer or oligomer as a result of a polycondensation reaction between a), b), c), and d).

### Claim 19 (depends on 1)

The composition of claim 1, wherein the polymer or oligomer comprises at least about 5 wt % of MRI contrast agent moiety based on the total number of moles of the comonomers of the polymer or oligomer.

### Claim 20 (depends on 1)

The composition of claim 1, wherein the metal-containing portion of the MRI contrast agent comprises a lanthanide-ion containing portion.

### Claim 21 (depends on 20)

The composition of claim 20, wherein the lanthanide-ion containing portion comprises a lanthanide metal ion of Gd, Nd, Sm, Eu, Tb, Dy, Ho, or Er.

### Claim 22 (depends on 20)

The composition of claim 20, wherein the lanthanide-ion containing portion comprises Gd3+.