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Pet radiotracers

Pet radiotracers description/claims

The invention relates to novel 18F-labelled compounds and their use as Positron Emission Tomography (PET) radiotracers, and to processes for preparation of such compounds. The invention further relates to kits for preparation of the compounds and to compositions comprising the 18F-labelled compounds.

The favoured radioisotope for PET, 18F, has a relatively short half-life of 110 minutes. 18F-labelled tracers for PET therefore have to be synthesised and purified as rapidly as possibly, and ideally within one hour of clinical use. PET tracers are frequently labelled with [18F]fluoroalkyl groups to produce [18F]fluoroalkylated PET tracers. [18F]fluorohaloalkanes are important reagents for performing O—, N—, and S—[18F]fluoroalkylations and are commonly used to radiolabel ligands for use in PET studies. Solid-phase preparations of [18F]fluorohaloalkanes are described in WO-A-2004/056726.

The PET tracers comprising [18F]fluoroalkyl groups may however suffer from in vivo defluorination wherein the [18F]fluoride is cleaved off from the rest of the tracer. This may lead to decreased signal and increased background noise signal mainly from uptake of [18F]fluoride in bone tissue. There is hence a clinical need for development of improved PET tracers which are more stable in vivo and there is a need for synthetic methods for their preparation in good radiochemical yield.

In view of these needs the present invention provides new compounds suitable as PET tracers. The compounds of the present invention provide an improved target/background signal ratio and increased specificity and sensitivity.

In a first aspect, the present invention provides a compound comprising a [18F]fluoroalkenyl group. The compounds are suitable for use as PET radiotracers. The compound is labelled with 18F either in the 1- or 2-position of an alkenyl group, providing 1-[18F]-fluoro-1-alkenylated and 2-[18F]-fluoro-1-alkenylated compounds.

The compounds of the invention comprise a [18F]fluoroalkenyl group, rather than a [18F]fluoroalkyl group, used in the state of the art. It has been found that the compounds of the invention to a less degree undergo in vivo defluorination compared to fluoroalkylated compounds and improved specificity and an increased target/background signal ratio is achieved. Haloalkenes, i.e. compounds of the invention, cannot undergo an SN2 substitution, and have therefore an increased resistance to dehalogenation, i.e. are more stable in vivo than the haloalkanes.

In one embodiment the invention provides 18F-labelled compounds of formula (I)

wherein X′ and X″ are independently selected from hydrogen and 18F, with the proviso that either of X′ or X″ is a 18F-atom; n is an integer from 1 to 5; the vector comprises a moiety having affinity for a biological target; and L represents a linker moiety.

A 18F-fluoroalkyl group of PET tracers of the state of the art can be substituted with a [18F]fluoroalkenyl group to provide a 18F-labelled compound of the invention.

The vector comprises a moiety that has affinity to a biological target, preferably which accumulates in biological targets due to their biological and/or physiological properties and therefore can be used to visualize biological structures, functions and pathological processes.

The vector may be of synthetic or natural origin, and is preferably synthetic. The vector has the ability to direct the compound to a region of a given disease. Preferably, the vector has affinity for the target, such as a biological receptor, and preferably binds to this. On the one hand the vector should have a high affinity for the receptor, and on the other hand it should “stay” on the receptor as long as necessary. The receptors may be located in the vascular system, in the extracellular space, associated with cell membranes or located intracellularly.

The vector can generally be any type of molecule that has affinity for a biological target. All vectors that can be linked to the fluoroalkenyl group without loosing their affinity to the biological target are relevant. The vector should be physiologically acceptable and should preferably have an acceptable degree of stability. The vector may comprise biomolecules, preferably selected from the group consisting of peptides, peptoids/peptidomimetics and proteins; oligonucleotides, such as oligo-DNA or oligo-RNA fragments; oligosaccharides; lipid-related compounds; hormones; synthetic small drug-like molecules; inhibitors; antibodies and antibody fragments; and derivatives and mimetics thereof.

• Provisional Patent
• Utility Patent

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