Methods and compositions for radiohalogen protein labeling

Patent metadata

Field	Value
Publication number	US-2016002121-A1
Application number	US-201514814734-A
Country	US
Kind code	A1
Filing date	Jul 31, 2015
Priority date	Dec 19, 2012
Publication date	Jan 7, 2016
Grant date	—

Abstract

Methods and compositions are provided for labeling proteins with radiohalogen-label reagents. Radiohalogen-labeled proteins may be used for imaging studies, as therapeutics and in diagnostic tests. The [ 125 I] HIP-DOTA label reagent 6 is prepared by an efficient and convenient process.

First claim

We claim:

1 . A radiohalogen-labeling reagent having the structure:

wherein
Hal is a radiohalide isotope selected from 123 I, 124 I, 125 I, 131 I, and 211 At;
L is a linker selected from —(C 1 -C 12 alkylene)-C(O)NR—(C 1 -C 12 alkylene)-, —(C 1 -C 12 alkylene)-C(O)NR—(C 1 -C 12 alkylene)O—, —(C 1 -C 12 alkylene)-C(O)NR—(C 1 -C 12 alkylene)-C(O)CH 2 —, —(C 1 -C 12 alkylene)-C(O)N(R)—, —(C 1 -C 12 alkylene)-C(O)NR—(C 2 -C 8 alkenylene)-, —(C 1 -C 12 alkylene)-C(O)NR—(C 2 -C 8 alkynylene)-, —(C 1 -C 12 alkylene)-C(O)NR(CH 2 CH 2 O) n —, —(C 1 -C 12 alkylene)-C(O)—, —(C 1 -C 12 alkylene)-C(O)NR(CH 2 CH 2 O) n CH 2 C(O)—, and —(C 1 -C 12 alkylene)-C(O)NR(CH 2 CH 2 O) n CH 2 —,
where n is 1 to 6, R is H, C 1 -C 12 alkyl, or C 6 -C 20 aryl, and
alkylene, alkenylene, alkynylene, alkyl, and aryl are optionally substituted with one or more groups selected from F, Cl, Br, I, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 CH 2 NH 2 , —CH 2 CHCH 2 NH 2 , —CH 2 CH(CH 3 )NH 2 , —CH 2 OH, —CH 2 OCH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 OCH 3 , —C(CH 3 ) 2 OH, —CH(OH)CH(CH 3 ) 2 , —C(CH 3 ) 2 CH 2 OH, —CH 2 CH 2 SO 2 CH 3 , —CN, —CF 3 , —CO 2 H, —COCH 3 , —CO 2 CH 3 , —CO 2 C(CH 3 ) 3 , —COCH(OH)CH 3 , —CONH 2 , —CONHCH 3 , —CON(CH 3 ) 2 , —C(CH 3 ) 2 CONH 2 , —NO 2 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NHCOCH 3 , —N(CH 3 )COCH 3 , —NHS(O) 2 CH 3 , —N(CH 3 )C(CH 3 ) 2 CONH 2 , —N(CH 3 )CH 2 CH 2 S(O) 2 CH 3 , ═O, —OH, —OCH 3 , —OP(O) 3 , —S(O) 2 N(CH 3 ) 2 , —S(O) 3 , —SCH 3 , and —S(O) 2 CH 3 ; and
E is a reactive functional group selected from maleimide, thiol, amino, bromide, bromoacetamido, p-toluenesulfonate, iodide, hydroxyl, carboxyl, aldehyde, pyridyl disulfide, N-hydroxysuccinimide, azido, isocyanato, isothiocyanato, and phosphoramidite.

2 . The radiohalogen-labeling reagent of claim 1 wherein E is maleimide.

3 . The radiohalogen-labeling reagent of claim 2 having the formula:

where I is an iodine isotope selected from 123 I, 124 I, 125 I, and 131 I.

4 . The radiohalogen-labeling reagent of claim 1 wherein E is N-hydroxysuccinimide.

5 . The radiohalogen-labeling reagent of claim 4 having the formula:

where I is an iodine isotope selected from 123 I, 124 I, 125 I, and 131 I.

Assignees

• Genentech Inc

Inventors

• Boswell Charles Andrew
• Khawli Leslie A
• Marik Jan
• Williams Simon

Classifications

• A61K51/0482 Primary

  chelates from cyclic ligands, e.g. DOTA · CPC title

• C07D207/404

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide · CPC title

• C07B59/002 Primary

  Heterocyclic compounds · CPC title

• C07D207/452

  with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom · CPC title

• A61K51/08

  Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins} · CPC title