1. A pressure regulator (500), comprising:
a housing (503);
a fluid inlet (508) to receive a pressurized fluid at an inlet pressure;
a fluid outlet (510) to output the pressurized fluid at a regulated pressure;
a regulating piston (504) movable within the housing (503) to provide fluid communication between the fluid inlet (508) and the fluid outlet (510) and including:
a first end (505) comprising a first cross-sectional width (D1) in fluid communication with the fluid inlet (508); and
a second end (509) comprising a second cross-sectional width (D2) in fluid communication with the fluid outlet (510);
wherein the first and second cross-sectional widths (D1, D2) are sized such that the regulated pressure at the fluid outlet (510) is correlated to the inlet pressure at the fluid inlet (508).
2. The pressure regulator (500) of claim 1, further comprising a valve seal (506) formed on the first end (505) of the regulating piston (504) and adapted to form a substantially fluid-tight seal with a valve seat (507) formed in the housing (503).
3. The pressure regulator (500) of claim 1, further comprising a biasing member (513) configured to bias the regulating piston (504) in a first direction.
4. The pressure regulator (500) of claim 3, wherein the first direction is towards the fluid outlet (510).
5. The pressure regulator (500) of claim 1, further comprising a fluid passage (511) formed in the regulating piston (504) and providing a fluid communication path between the fluid inlet (508) and the fluid outlet (510).
6. The pressure regulator (500) of claim 1, further comprising a cap (502) coupled to the housing (503) and adapted to retain the regulating piston (504) at least partially within the housing (503).
7. The pressure regulator (500) of claim 1, wherein the second cross-sectional width (D2) is greater than the first cross-sectional width (D1).
8. A method of forming a pressure regulator including a housing, a fluid inlet to receive a pressurized fluid at an inlet pressure, and a fluid outlet to output the pressurized fluid at a regulated pressure, comprising steps of:
positioning a regulating piston movably within the housing to provide fluid communication between the fluid inlet and the fluid outlet;
locating a first end of the regulating piston comprising a first cross-sectional width in fluid communication with the fluid inlet; and
locating a second end of the regulating piston comprising a second cross-sectional width in fluid communication with the fluid outlet;
wherein the first and second cross-sectional widths are sized such that the regulated pressure at the fluid outlet is correlated to the inlet pressure at the fluid inlet.
9. The method of claim 8, further comprising a step of forming a valve seal on the first end of the regulating piston that is adapted to form a substantially fluid-tight seal with a valve seat formed in the housing.
10. The method of claim 8, further comprising a step of positioning a biasing member within the housing and configured to bias the regulating piston in a first direction.
11. The method of claim 10, wherein the first direction is towards the fluid outlet.
12. The method of claim 8, further comprising a step of forming a fluid passage in the regulating piston to provide a fluid communication path between the fluid inlet and the fluid outlet.
13. The method of claim 8, further comprising a step of coupling a cap to the housing that is adapted to retain the regulating piston at least partially within the housing.
14. The method of claim 8, wherein the second cross-sectional width is greater than the first cross-sectional width.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for radiofluorination comprising reaction of a compound of formula (I) with a compound of formula (II):
or,
a compound of formula (III) with a compound of formula (IV)
wherein
R1 is a halogen-containing moiety;
R2 is an N-alkyl aminooxy group;
R3 is an N-alkyl aminoxy group; and
R4 is a is a halogen-containing moiety;
to give a conjugate of formula (V) or (VI) respectively:
wherein Y is alkyl or aryl and the 18F-Linker group in the compounds of formulae (II) and (V) is selected from a group of synthons comprising an N-alkyl aminoxy moiety linked to the 18F atom via stable bonds and the 18F-Linker group in the compounds of formula (IV) and (VI) is selected from the halogen-containing synthons.
2. A method of claim 1, wherein R1 is a haloacetyl or phenacylhalo group.
3. A method of claim 1, wherein R4 is a haloacetyl or phenacylhalo group.
4. A method of claim 1, wherein Y is methyl.
5. A method of claim 1, wherein the 18F-Linker group in the compounds of formulae (II) and (V) is selected from
wherein:
V is a halogen atom preferably bromine, chlorine or iodine
n is an integer of 0 to 20;
Z is O, N or S.
6. A method of claim 1, wherein the 18F-Linker group in the compounds of formula (IV) and (VI) is selected from
wherein:
V is a halogen atom preferably bromine, chlorine or iodine
n is an integer of 0 to 20;
Z is O, N or S.
7. A method for radiofluorination comprising reaction of a compound of formula (Ia) with a compound of formula (IIa):
or,
a compound of formula (Ma) with a compound of formula (IVa)
wherein R1 and R4 are as defined above for the compounds of formula (I) and (IV) respectively; the Linker group in the compounds of formulae (IIa) and (IVa) are each a C1-60 hydrocarbyl group, suitably a C1-30 hydrocarbyl group, optionally including 1 to 30 heteroatoms, suitably 1 to 10 heteroatoms such as oxygen or nitrogen, to give a conjugates of formula (Va) or (VIa) respectively:
wherein the Linker group is as defined for the compound of formula (IIa) or (IVa).
8. A method of claim 7, wherein the Linker group is selected from alkyl, alkenyl, alkynyl chains, aromatic, polyaromatic, and heteroaromatic rings, and polymers comprising ethyleneglycol, amino acid, or carbohydrate subunits.
9. A method for radiofluorination comprising reaction of a compound of formula (VIIa):
with a compound of formula (VIIb)
18F-Linker-V (VIIb)
to give a compounds of formula (VIIc)
18F-Linker-NH(Y)\u2014O-Vector (VIIc),
wherein Y is an alkyl or aryl substituents.
10. A method of claim 9, wherein compound (VIIb) is selected from (VIII), (IX) or (X)
to give compounds of formula (XII-XV) respectively:
18F\u2014(CH2CH2O)nCH2CH2-NHCOCH2-N(Y)\u2014O-Vector (XII)
18F\u2014(CH2)n-N(Y)\u2014O-Vector (XIII)
18F\u2014(C6H4)\u2014CO\u2014CH2-N(Y)\u2014O-Vector (XIV)
wherein:
n is an integer of 0 to 20;
Y is an alkyl or aryl substituents.
11. A method for radioflurination comprising reaction of a compound of formula (XVa):
where V is a halogen with compounds of the general formula (XVb)
18F-Linker-O\u2014NH(Y) (XVb)
wherein Y is as defined for the previous compounds.
12. A method of claim 11, wherein compound of formula (XVb) is selected from compounds of the formula (XVI), (XVII),(XVIII)
wherein Y, m and n are as defined for the previous compounds.
13. A method of claim 1, wherein the vector is Arg-Gly-Asp peptide or an analogue thereof.
14. A method of claim 13, wherein the vector comprises the fragment
15. A method of claim 13, wherein the vector is of formula (A):
wherein X7 is either \u2014NH2 or
wherein a is an integer of from 1 to 10, and where R5 forms an amide bond or a secondary amine bond with the \u03b5-amino of the lysine residue following reaction of the peptide and is preferably chosen from the list i-viii below.
where R6 is an active ester activating group such as an N-hydroxysuccinimide or acid chloride and L and V are as described previously.
16. A compound of formula (I) or (III) as defined in claim 1.
17. A compound of claim 16, wherein the vector is Arg-Gly-Asp peptide or an analogue thereof.
18. A compound of claim 16, wherein the vector comprises the fragment
19. A compound of claim 16, wherein the vector is of formula (A):
wherein X7 is either \u2014NH2 or
wherein a is an integer of from 1 to 10, and where R5 forms an amide bond or a secondary amine bond with the \u03b5-amino of the lysine residue following reaction of the peptide and is preferably chosen from the list i-viii below.
where R6 is an active ester activating group such as an N-hydroxysuccinimide or acid chloride and L and V are as described previously.
20. A compound of formulae (V) or (VI) as defined in claim 1.
21. A compound of claim 20, wherein the vector is Arg-Gly-Asp peptide or an analogue thereof.
22. A compound of claim 20, wherein the vector comprises the fragment
23. A compound of claim 20, wherein the vector is of formula (A):
wherein X7 is either \u2014NH2 or
wherein a is an integer of from 1 to 10, and where R5 forms an amide bond or a secondary amine bond with the \u03b5-amino of the lysine residue following reaction of the peptide and is preferably chosen from the list i-viii below.
where R6 is an active ester activating group such as an N-hydroxysuccinimide or acid chloride and L and V are as described previously.
24. A radiopharmaceutical composition comprising an effective amount of a compound of claim 20, together with one or more pharmaceutically acceptable adjuvants, excipients or diluents.
25. A compound of claim 20 for medical use.
26. Use of a compound of claim 20 for the manufacture of a radiopharmaceutical for use in the method of in vivo imaging.
27. A method of generating an image of a human or animal body comprising administering a compound of claim 20 to said body and generating an image of at least a part of said body to which said compound has distributed using PET.
28. A method of monitoring the effect of treatment of a human or animal body with a drug to combat a condition associated with cancer, preferably angiogenesis, said method comprising administering to said body a compound of claim 21 and detecting the uptake of said compound by cell receptors said administration and detection optionally but preferably being effected before, during and after treatment with said drug.