Detectable molecules, method of preparation and use

• US 4,849,208 A
• Filed: 04/28/1987
• Issued: 07/18/1989
• Est. Priority Date: 01/30/1984
• Status: Expired due to Term

• Current Assignee: Enzo Therapeutics Incorporated (Enzo Biochem Incorporated)
• Original Assignee: Enzo Biochem Incorporated
• Inventors: Stavrianopoulos, Jannis G.
• Primary Examiner(s): Nucker, Christine M.
• Application Number:
  US07/043,577
• Time in Patent Office: 812 Days
• Field of Search: 424/1.1, 424/9, 128/1.1, 128/654, 128/659
• US Class Current: 424/1.53
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: A61K 51/1093 conjugates with carriers being antibodies
• CPC Class Codes: G01N 33/533 with fluorescent label
• CPC Class Codes: G01N 33/553 Metal or metal coated

Abstract

A detectable molecule of the formula

A.sup.3 --(--X--R.sup.1 --E--Det.sup.b).sub.m

wherein A³ is A² or a polymer, where A³ has at least one modifiable reactive group selected from the group consisting of amino, hydroxy, cis .OH, halides, aryl, imidazoly, carbonyl, carboxy, thiol or a residue comprising an activated carbon; --X-- is selected from the group consisting of ##STR1## a C₁ -C₁₀ branched or unbranched alkyl or aralkyl, which may be substituted by --OH; --Y-- is a direct bond to --E--, or --Y-- is --E--R² -- where R² is a C₁ -C₁₀ branched or unbranched alkyl; Z_a is chlorine, bromine or iodine; E is O, NH or an acyclic divalent sulfur atom; Det^b is a chemical moiety capable of being detected, preferably comprising biotin or a metal chelator of the formula: ##STR2## or the 4-hydroxy or acyloxy derivative thereof, where R³ is C₁ -C₄ alkyl or CH₂ COOM, M is the same or different and selected from the group consisting of hydrogen, a metal or non-metal cation or is C₁ -C₁₀ alkyl, aryl or aralkyl; and mm is an integer from 1 to the total number of modified reactive groups on A³. The detectable molecules are useful in in vitro or in vivo assays or therapy.

Claims

1. An imaging procedure which comprises:

administering to an individual a detectable molecule of the formula A³ --(X--R¹ --E--Det^b)_m where A³ is A² or a polymer, both A² and the polymer having at least one modifiable reactive group consisting of amino, hydroxy, cis OH, halide, aryl, imidazoyl, carbonyl, carboxyl, thiol or a residue comprising an activated carbon;

A² is a specific binding ligand having a molecular weight of less than about 2,000;

--X-- is selected from the group consisting of ##STR52## or a C₁ -C₁₀ branched or unbranched alkyl or aralkyl, which may be substituted by --OH;

--Y-- is a direct bond to --E--, or --Y-- is --E--R² -- where --R² --is a C₁ -C₁₀ branched or unbranched alkyl;

Z_a is chlorine, bromine or iodine;

--E-- is O, NH or an acyclic divalent sulfur atom;

Det^b is a metal chelator which has the formula;

##STR53## or the 4-hydroxy or acyloxy derivative thereof, where R3 is Cl-C4 alkyl or is --CH2--COOM, and each M is a metal or non-metal cation; and

m is an integer from 1 to the total number of modified reactive groups on A³ ; and

, thereafter,

observing the distribution of said compound in said individual.

2. The imaging procedure of claim 1 which comprises administering said detectable molecule wherein Det^b is a metal chelator having the formula and M is a radiometal.

3. A method of radiation therapy which comprises administering to a human or animal situs a therapeutically effective amount of a radiometal chelated with a detectable molecule of the formula A³ --(X--R¹ --E--Det^b)_m where A³ is an antibody specific for said human or animal situs

--X-- is selected from the group consisting of ##STR54## or a C₁ -C₁₀ branched or unbranched alkyl or aralkyl, which may be substituted by --OH;

--Y-- is a direct bond to --E--, or --Y-- is --E--R² -- where --R² -- is a C₁ -C₁₀ branched or unbranced alkyl;

Z_a is chlorine, bromine or iodine;

--E-- is O, NH or an acyclic divalent sulfur atom;

Det^b is a metal chelator which has the formula;

##STR55## or the 4-hydroxy or acyloxy derivative thereof, where R3 is Cl-C4 alkyl or is --CH2--COOM, and each M is a metal or non-metal cation; and

m is an integer from 1 to the total number of modified reactive groups on A³ .

4. The method of claim 3 wherein said antibody is a human monoclonal antibody.