Halogenated neuroprobe for mapping monoamine reuptake sites

• US 5,750,089 A
• Filed: 01/11/1996
• Issued: 05/12/1998
• Est. Priority Date: 01/11/1996
• Status: Expired due to Term

• Current Assignee: GE Healthcare Limited (General Electric Company)
• Original Assignee: Neuro Imaging Technologies, LLC
• Inventors: Tamagnan, Gilles, Neumeyer, John L., Milius, Richard A., Wang, Shaoyin
• Primary Examiner(s): Hollinden, Gary E.
• Assistant Examiner(s): Hartley, Michael G.
• Application Number:
  US08/584,617
• Time in Patent Office: 852 Days
• Field of Search: 424/1.85, 424/1.81, 424/1.73, 514/304, 546/124, 540/466
• US Class Current: 424/1.85
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 51/0448 tropane or nortropane groups, e.g. cocaine
• 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= ##STR2## wherein n=2-8; 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.

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

Claims

1. A neuroprobe having the formula:

##STR5## wherein R= ##STR6## wherein n=2-8;

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 said isotope of I is ¹²³ I.

3. The neuroprobe of claim 1, wherein said isotope of I is ¹²⁵ I.

4. The neuroprobe of claim 1, wherein said isotope of I is ¹³¹ I.

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

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

a precursor of the formula;

##STR7## wherein R= ##STR8## wherein n=2-8;

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

X=a non-radioactive isotope of Cl, a nonradioactive isotope of Br, a non-radioactive isotope of F, a non-radioactive 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.

7. The kit of claim 6, wherein the precursor is reacted in the presence of a radioisotope source.

8. The kit of claim 7, wherein the radioisotope source is a solution of a salt of a radioactive isotope of iodine, and the reaction takes place in the presence of an oxidizing agent.

9. The kit of claim 8, wherein said radioactive isotope of iodine is ¹²³ I.

10. The kit of claim 8, wherein said radioactive isotope of iodine is ¹²⁵ I.

11. The kit of claim 8, wherein said radioactive isotope of iodine ¹³¹ I.

12. The kit of claim 7, wherein said radioisotope source is ¹⁸ F.

13. The kit of claim 12, wherein the radioisotope source is selected from the group consisting of Na¹⁸ F, K¹⁸ F, and Cs¹⁸ F.

14. The kit of claim 12, 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.

15. The kit of claim 6, wherein in R'"'"', C includes a radioactive isotope of carbon.