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US 11,135,322 B2Granted
Radiofluorination method
AssigneesGe Healthcare Limited, University of Southampton
InventorsRajiv Bhalla, Sajinder Kaur Luthra, Gill Reid, I, William Levason
Life of this patent
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Abstract
The present invention relates to a method of labelling biological molecules with 18F, via attachment to fluorine to a macrocyclic metal complex of a non-radioactive metal, where the metal complex is conjugated to the biological molecule. Also provided are pharmaceutical compositions, kits and methods of in vivo imaging.
Claims19
An imaging agent which comprises an 18F-labelled compound of Formula I:
- where:
- Y1 and Y2 are independently O or NR1, where R1 is C1-3 alkyl or —CH2—Ar1, wherein Ar1 is C5-12 aryl or C3-12 heteroaryl;
- X1, X2 and X3 are independently 19F or 18F, with the proviso that at least one of X1, X2 and X3 is 18F and at least one of the remaining X1, X2, and X3 is 19F;
- M is Al3+, Ga3+, In3+, Se3+, Y3+, Ho3+, Er3+, Tm3+, Yb3+or Lu3+;
- x, y and z are 1;
- R2 is R1 or Q;
- Q is -L-[BTM], and may be present or absent;
- when present it is either R2 or is attached at one of the carbon atoms of the —(CH2)(CH2)x—, —(CH2)(CH2)y— or —(CH2)(CH2)z— groups, where BTM is a biological targeting moiety;
- wherein L is a synthetic linker group of formula -(A)m- wherein each A is independently —CR32—, —CR3═CR3—, —C═C—, —CR32CO2—, —CO2CR32—, —NR3CO—, —CONR3—, —CR3═N—O—, —NR3(C═O) NR3—, —NR3(C═S)NR3—, —SO2NR3—, —NR3SO2, —CR32OCR32, —CR32SCR32, —CR32NR3CR32—, a C4-8 cycloheteroalkylene group, a C4-8 cycloalkylene group, —Ar2—, —NR3—Ar2—, —O—Ar2—, —Ar2—(CO)—, an amino acid, a sugar or a monodisperse polyethyleneglycol (PEG) building block,
- wherein each R3 is independently chosen from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxyalkyl or C1-4 hydroxyalkyl;
- m is an integer of value 1 to 20;
- and
- each Ar2 is independently a C5-12 arylene group, or a C3-12 heteroarylene group.
10 more elements
An imaging agent which comprises an 18F-labelled compound of Formula IA:
- where:
- Y1 and Y2 are NR1, where R1 is C1-3 alkyl or —CH2—Ar1, wherein Ar1 is C5-12 aryl or C3-12 heteroaryl;
- X1, X2 and X3 are independently 19F or 18F, with the proviso that at least one of X1, X2 and X3 is 18F and at least one of the remaining X1, X2, and X3 is 19F;
- M is Ga3+ or In3+;
- x, y and z are 1;
- Q is -L-[BTM], where BTM is a biological targeting moiety;
- wherein L is a synthetic linker group of formula -(A)m- wherein each A is independently —CR32—, —CR3=CR3—, —C═C—, —CR32CO2—, —CO2CR32—, —NR3CO—, —CONR3—, —CR3═N—O—, —NR3(C═O) NR3—, —NR3(C═S)NR3—, —SO2NR3—, —NR3SO2, —CR32OCR32, —CR32SCR32, —CR32NR3CR32—, a C4-8 cycloheteroalkylene group, a C4-8 cycloalkylene group, —Ar2—, —NR3—Ar2—, —O—Ar2—, —Ar2—(CO)—, an amino acid, a sugar or a monodisperse polyethyleneglycol (PEG) building block;
- wherein each R3 is independently chosen from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxyalkyl or C1-4 hydroxyalkyl;
- m is an integer of value 1 to 20;
- and
- each Ar2 is independently a C5-12 arylene group, or a C3-12 heteroarylene group.
8 more elements
Dependencies are inferred from the claim text.