Radioisotope trithiol complexes
The present invention is directed to a series of stable radioisotope trithiol complexes that provide a simplified route for the direct complexation of radioisotopes present in low concentrations. In certain embodiments, the complex contains a linking domain configured to conjugate the radioisotope trithiol complex to a targeting vector. The invention is also directed to a novel method of linking the radioisotope to a trithiol compound to form the radioisotope trithiol complex. The inventive radioisotope trithiol complexes may be utilized for a variety of applications, including diagnostics and/or treatment in nuclear medicine.
1. A radioisotope trithiol complex according to Formula I:
wherein each R 1 is independently C 1 to C 5 substituted or unsubstituted hydrocarbyl;
m M is a radioisotope; and
X is a chemical moiety.
2. The complex of claim 1 , which X is a linking domain comprising a functional group.
3. The complex of claim 2 , wherein said functional group is selected from the group consisting of phosphonic acid, isothiocyanate, maleimide, carboxylic acid, primary amine, aldehyde, sulfonyl chloride, secondary amine, hydroxide, aryl-NCS, alkene, alkyne, azide, active esters, thiol, CH 2 OH, CH 2 OCH 3 , CH 2 OCOCH 3 , COOC 2 H 5 , CONHC 3 H 7 , CO-Phe-OC 2 H 5 , CO-Phe-OH, CO-Phe-Ala-OH, CO-Phe-Met-OCH 3 , and CO-Phe-Phe-Gly-Leu-Met-NH 2 .
4. The complex of claim 2 , further comprising a targeting vector conjugated to the linking domain.
5. The complex of claim 4 , wherein the targeting vector is selected from the group consisting of peptides, antibodies, oligonucleotides, carbohydrates, lipids, and organic molecules.
6. The complex of claim 5 , wherein the targeting vector is selected from the group consisting of peptides and antibodies.
7. The complex of claim 2 , wherein linking domain X comprises a spacer.
8. The complex of claim 1 , wherein m M is selected from the group consisting of a radioisotope of arsenic, lead, mercury, silver, copper, platinum, lanthanides, actinides, rhenium, nickel, bismuth, technetium, gallium, rhodium and zinc.
9. The complex of claim 8 , wherein m M is a radioisotope of arsenic.
10. The complex of claim 1 , wherein each R 1 has the same number of carbon atoms.
11. The complex of claim 10 , wherein each R 1 is a methyl group.
12. A method for making the radioisotope trithiol complex of claim 1 , comprising:
reacting the radioisotope m M with a trithiol complex of Formula V:
wherein X and R 1 are defined as in claim 1 .
13. The method of claim 12 , wherein m M is a radioisotope of arsenic.
14. The method of claim 12 , wherein the radioisotope is present in a concentration lower than 20 μM.
15. A method of using the radioisotope trithiol complex of claim 1 in nuclear medicine.
16. A radioisotope trithiol complex according to Formula I:
wherein each R 1 is a C 1 to C 5 substituted or unsubstituted hydrocarbyl having the same number of carbon atoms;
m M is a radioisotope; and
X is a linking domain comprising a functional group.
17. The complex of claim 16 , further comprising a targeting vector conjugated to the linking domain.
18. The complex of claim 17 , wherein the targeting vector is selected from the group consisting of peptides, antibodies, oligonucleotides, carbohydrates, lipids, and organic molecules.
19. The complex of claim 16 , wherein each R 1 is methyl.
20. The complex of claim 16 , wherein m M is a radioisotope of arsenic.