Metallocene compounds and labeled molecules comprising the same for in vivo imaging

摘要

The present invention concerns compounds and methods of labeling peptides or other molecules with 18F or 19F or any other suitable radionuclide of use, for example, in PET or NMR in vivo imaging. A targeting molecule such as a protein or a peptide is linked to a substituted metallocene complex which is reacted with the 1gF or 19F shortly before performing the PET or NMR in vivo imaging on the patient. The labeled molecule is then used for targeting a cell, tissue, organ or pathogen to be imaged or detected.;

主权项

1. Metallocene compound of general formula (I):wherein:
M is a metal selected from the group consisting of titanium, zirconium and hafnium; X1 and X2, which can be the same or different, are a halogen atom, a R′, OR′, OCOR′, SR′, NR′2 or PR′2 group, wherein the R′ substituents are linear or branched, saturated or unsaturated C1-C20 alkyl, C3-C20 cycloalkyl, C6-C20 aryl, C7-C20 alkylaryl, C7-C20 arylalkyl radicals, optionally containing one or more heteroatoms belonging to the groups 13-17 of the Periodic Table of the Elements; X1 and X2 can also be interconnected via a cyclic structure of <40 atoms comprising one or more of C, N, O, F, Si, B, P; R1, R2, R3, R4, R5, R6, R7, R8 and R9, the same or different, are H or linear or branched, saturated or unsaturated C1-C20 alkyl, C3-C20 cycloalkyl, C6-C20 aryl, C7-C20 alkylaryl, C7-C20 arylalkyl radicals, optionally containing one or more heteroatoms belonging to the groups 13-17 of the Periodic Table of the Elements; two or more adjacent R1, R2, R3, R4, R5, R6, R7, R8 and R9 groups on a cyclopentadienyl residue may be connected by a saturated or unsaturated bridge containing up to 40 atoms comprising one or more of C, N, S, O, F, Si, B, P, said bridge optionally containing or being part of up to 5 carbo- or hetero-cycles; L is a linker having a functional end, selected from the group consisting of:wherein:
Ph=phenyl; X=R′NH, in which R′ is as defined above; R is selected from the group consisting of F, CH2F, CHF2, CF3, OCF3; Ar is C6-C20 aryl, C7-C20 alkylaryl, or C7-C20 arylalkyl radical, optionally containing one or more heteroatoms belonging to the groups 13-17 of the Periodic Table of the Elements; m=2-20; wherein the functional end of said linker group L is optionally protected.