Iodinated neuroprobe for mapping monoamine reuptake sites

• US 5,698,179 A
• Filed: 06/06/1995
• Issued: 12/16/1997
• Est. Priority Date: 02/25/1992
• Status: Expired due to Term

• Current Assignee: GE Healthcare Limited (General Electric Company)
• Original Assignee: Neuro Imaging Technologies, LLC
• Inventors: Neumeyer, John L., Innis, Robert B., Milius, Richard A.
• Primary Examiner(s): Hollinden, Gary E.
• Assistant Examiner(s): Hartley, Michael G.
• Application Number:
  US08/468,575
• Time in Patent Office: 924 Days
• Field of Search: 424/1.85, 424/1.81, 514/304, 546/124
• US Class Current: 424/1.85
• CPC Class Codes: C07D 451/02 containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof

Abstract

An iodinated neuroprobe is provided for mapping monoamine reuptake sites. The iodinated neuroprobe is of the formula: ##STR1## wherein: R=aryl, substituted aryl, heterocyclic, CO(CH₂)_n Y, (CH₂)_n CHF₂, and (CF₂)_n Y, wherein:

Y=Cl, Br, I, (CH₂)_m, aryl, substituted aryl, heterocyclic CO₂ H, CO₂ R³, CO₂ NR³ R⁴, OH, OR³, CH(OR³)₂, CR³ (OR⁴)₂, OC0R³, OSO₂ R³, OCONR³ R⁴, OCOOR³, CONR³ R⁴, NR³ R⁴, NR³ COR⁴, NR³ CO₂ R⁴, NR³ CONR⁴ R⁵, NCS, NCO;

R³, R⁴ and R⁵ =alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, or heterocyclic;

m=3-8; and

n=1-6;

R'"'"'=C_w H_2w+1 wherein w=0-6 and C includes an isotope of carbon; and

X=an isotope of Cl, an isotope of Br, an isotope of F, an isotope of I, or Sn(R"₁ R"₂ R"₃), wherein

R"₁ =a C_p H_2p+1 group where p=1-6, or an aryl group;

R"₂ =a CH_p+1 group where p=1-6, or an aryl group; and

R"₃ =a C_p H_2p+1 group where p=1-6, or an aryl group.

Related analogs are also provided. Additionally, a precursor of a radiolabeled neuroprobe and a kit for preparing the iodinated neuroprobe are provided.

Claims

1. A neuroprobe for mapping monoamine reuptake sites, the neuroprobe having the formula:

##STR3## wherein R=(CH₂)_n OSO₂ R³ ;

wherein R³ =alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, and heterocyclic; and

n=1-6;

R'"'"'=C_w H_2w+1 wherein w=0-6 and C includes an isotope of carbon; and

X=an isotope of Cl, an isotope of Br, an isotope of F, an isotope of I, or Sn(R"₁ R"₂ R"₃), wherein

R"₁ =a C_p H_2p+1 group where p=1-6, or an aryl group;

R"₂ =a C_p H_2p+1 group where p=1-6, or an aryl group; and

R"₃ =a C_p H_2p+1 group where p=1-6, or an aryl group.

2. The neuroprobe of claim 1, wherein the iodine atom is a radioactive isotope of iodine.

3. The neuroprobe of claim 2, wherein the radioactive isotope of iodine is selected from the group consisting of ¹²³ I, ¹²⁵ I, and ¹³¹ I.

4. The neuroprobe of claim 1, wherein in R'"'"', C includes a radioactive isotope of carbon.

5. A kit for preparing a radiolabeled neuroprobe for mapping monoamine reuptake sites, the kit comprising:

a precursor of the formula;

##STR4## wherein R=(CH₂)_n OSO₂ R³ ;

wherein R³ =alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, and heterocyclic; and

n=1-6;

R'"'"'=C_w H_2w+1 wherein w=0-6 and C includes an isotope of carbon; and

X=an isotope of Cl, an isotope of Br, an isotope of F, an isotope of I, or Sn (R"₁ R"₂ R"₃) wherein

R"₁ =a C_p H_2p+1 group where p=1-6 or an aryl group;

R"₂ =a C_p H_2p+1 group where p=1-6 or an aryl group; and

R"₃ =a C_p H_2p+1 group where p=1-6, or an aryl group.

6. The kit of claim 5, wherein said isotope of I is a radioactive isotope of iodine.

7. The kit of claim 6, wherein said isotope of I is selected from the group consisting of ¹²³ I, ¹²⁵ I, and ¹³¹ I.

8. The kit of claim 6, wherein the precursor is reacted in the presence ¹⁸ F.

9. The kit of claim 8, wherein the ¹⁸ F is selected from the group consisting of Na¹⁸ F, K¹⁸ F, and Cs¹⁸ F.

10. The kit of claim 8, wherein said ¹⁸ F is complexed with a reagent of the formula M⁺ X^-, wherein:

M⁺ =a complex of 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo 8.8.8!hexacosane and one of K, Na, Ce, Ru, a tetraalkylammonium ion, and an ion exchange resin functionalized with quaternary amine groups; and

X^- =carbonate, bicarbonate, hydroxide, and formate.

11. The kit of claim 5, wherein in R'"'"', C includes a radioactive isotope of carbon.