Psma targeted radiohalogenated urea-polyaminocarboxylates for cancer radiotherapy
AssigneesThe Johns Hopkins University, Duke University
InventorsMartin G. Pomper, Ronnie C. Mease, Vivek Kumar, Sangeeta Ray, Michael Zalutsky, Ganesan Vaidyanathan
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Abstract
Small molecule radiohalogenated PSMA inhibitors and metal complexes thereof and their use in radioimaging and radiotherapy for treating PSMA-related diseases, including prostate cancer, are disclosed. The combination of small molecule radiohalogenated PSMA inhibitors with a competitive PSMA ligand for reducing off-target accumulation of the radiohalogenated PSMA inhibitor also is disclosed.
Claims27
1-11. (canceled)
A compound of the following formula:
- wherein:
- p is an integer selected from the group consisting of 1, 2, 3, 4, 5, and 6;
- and
- X is halogen;
- X1 is —CR3 or N, wherein R3 is H or C1-C4 alkyl;
- and
- X2 is selected from the group consisting of a radioisotope of iodine, a radioisotope of bromine, and a radioisotope of astatine;
- and
- wherein M+ is a metal, which can be present or absent.
A method for treating one or more PSMA expressing tumors or cells, the method comprising administering or contacting the one or more PSMA expressing tumors or cells with an effective amount of a compound of claim 2.
A one-pot, multi-step synthesis method for preparing a radiotherapeutic compound of formula (Ia):
- wherein X is a radiohalide, the method comprising:
- (a) providing a precursor compound of formula (Ia′):
- (b) contacting the precursor compound of formula (Ia′) with solution comprising a radiohalide and N-chlorosuccinimide, followed by the addition of glacial acetic acid to form a radiohalogenated precursor compound of formula (Ia″):
- (c) contacting the radiohalogenated precursor compound of formula (Ia″) with trifluoroacetic acid to form a radiohalogenated compound of formula (Ia′″):
- (d) contacting the radiohalogenated compound of formula (Ia′″) with NaOAc and Lu(NO3)3 to form a radiotherapeutic compound of formula (Ia).
A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
A kit for treating one or more PSMA expressing tumors or cells, the kit comprising a compound of claim 2.
(canceled)
Dependencies are inferred from the claim text.