Brush-arm star polymer imaging agents and uses thereof
AssigneesMassachusetts Institute of Technology, Board of Regents of the University of Nebraska
InventorsJeremiah A. Johnson, Hung Vanthanh Nguyen, Andrzej Rajca
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Abstract
Disclosed are methods, compositions, reagents, systems, and kits to prepare nitroxide-functionalized brush-arm star polymer organic radical contrast agent (BASP-ORCA) as well as compositions and uses thereof. Various embodiments show that BASP-ORCA display unprecedented per-nitroxide and per-molecule transverse relaxivities for organic radical contrast agents, exceptional stability, high water solubility, low in vitro and in vivo toxicity, and long blood compartment half-life. These materials have the potential to be adopted for tumor imaging using clinical high-field 1H MRI techniques.
Claims25
A brush-arm star polymer comprising one or more repeating units of Formula (I) and one or more repeating units of Formula (II):
- or a salt thereof, wherein:
- the combined number of repeating units of Formula (I) and repeating units of Formula (II) is at least 100;
- each A is independently C1-C12 alkylene or C1-C12 heteroalkylene, wherein each of the alkylene and heteroalkylene is independently optionally substituted with 1-2;
- each A1 is C1-C12 heteroalkylene, wherein each of the heteroalkylene is independently optionally substituted with 1-2 oxo;
- each B is C1-C12 alkylene, wherein each of the alkylene is independently optionally substituted with one oxo;
- each X is an imaging agent, wherein at least one imaging agent is an organic nitroxide radical-containing imaging agent;
- each P is a polyethylene glycol;
- each instance of L is independently selected from the group consisting of C1-C12 alkylene, C1-C12 heteroalkylene, (C0-C12 alkylene)-arylene-(C0-C12 alkylene), (C0-C12 heteroalkylene)-arylene-(C0-C12 alkylene), (C0-C12 alkylene)-arylene-(C0-C12 heteroalkylene), (C0-C12 heteroalkylene)-arylene-(C0-C12 heteroalkylene), (C0-C12 alkylene)-heteroarylene-(C0-C12 alkylene), (C0-C12 heteroalkylene)-heteroarylene-(C0-C12 alkylene), (C0-C12 heteroalkylene)-heteroarylene-(C0-C12 heteroalkylene), and a combination of any two thereof;
- wherein:
- each of the alkylene, heteroalkylene, arylene, and heteroarylene is independently optionally substituted with 1-24 independently selected R1 selected from the group consisting of alkyl, heteroalkyl, halo, cyano, oxo, nitro, —ORA, —N(RA)2, —NRAC(O)RA, —NRAC(O)ORA, —NRAC(O)N(RA)2, —C(O)N(RA)2, —C(O)RA, —C(O)ORA, —OC(O)RA, —OC(O)ORA, —OC(O)N(RA)2, —SRA, and —S(O)mRA;
- each of the heteroarylene is independently monocyclic, 5- or 6-membered heteroarylene;
- each RA is independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 haloalkyl;
- each m is independently 1 or 2;
- and
- each of p and o are independently an integer between 0 and 20, inclusive;
- each of a and b is 1;
- when “1”, “2”, “3”, “4”, “5”, and/or “6” shown in Formula (I) or Formula (II) are terminal groups, the terminal groups are independently selected from the group consisting of optionally substituted alkenyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
- and
- each y is independently an integer between 1 and 100, inclusive.
Dependencies are inferred from the claim text.