in a first aspect , the present invention provides an imaging agent which comprises a synthetic compound having affinity for chemokine receptor 5 ( ccr5 ) and having a molecular weight of 3000 daltons or less , labelled with at least one imaging moiety , wherein following administration of said compound to the mammalian body in vivo , the imaging moiety can be detected externally in a non - invasive manner and said imaging moiety is chosen from : a compound having “ affinity for ccr5 ” is defined in the present invention as that which inhibits binding of mip - 1β ccr5 - expressing cho cells with ic 50 values of between 0 . 1 nm to 10 nm , where mip - 1β is macrophage inflammatory protein 1β ( ligand of ccr5 ) [ samson et al ., j . biol . chem ., 272 , 24934 - 41 ( 1997 )]. see also example 4 . the ccr5 compounds of the present invention are also preferably selective for ccr5 over other chemokine receptors ( such as ccr1 or ccr3 ). such selective inhibitors suitably exhibit a greater potency for ccr5 over ccr1 , defined by ki , of a factor of at least 50 , preferably at least 100 , most preferably at least 500 . the synthetic compound is preferably a non - peptide . by the term “ non - peptide ” is meant a compound which does not comprise any peptide bonds , i . e . an amide bond between two amino acid residues . the synthetic compound having affinity for chemokine receptor 5 ( ccr5 ) preferably has a molecular weight of 1000 daltons or less , and most preferably 600 daltons or less . the synthetic compound preferably comprises 2 to 6 , most preferably 2 to 5 nitrogen ( n ) atoms . said n atoms are present as part of amide ; amine ; or 5 - or 6 - membered nitrogen - containing heteroaryl ring functional groups . the heteroaryl ring can have 1 or 2 n heteroatoms . when an amine is present , it is suitably either open chain or as part of a 5 - or 6 - membered saturated aliphatic ring . preferred such cyclic amines are piperidine , piperazine or morpholine . when an amide is present , it is suitably open chain , i . e . does not comprise a lactam . preferred such amides are benzamides or acyl derivatives of aniline , benzylamine or aminopiperidine residues . the synthetic compound also preferably comprises 1 to 3 phenyl rings , most preferably 1 or 2 phenyl rings . the ccr5 pharmacophore preferably comprises two hydrogen bond acceptors and three hydrophobic interactions ; in particular it has a basic amine located 5 - 7 å from a phenyl ring . the term “ labelled with ” means that either a functional group comprises the imaging moiety , or the imaging moiety is attached as an additional species . when a functional group comprises the imaging moiety , this means that the ‘ imaging moiety ’ forms part of the chemical structure , and is a radioactive isotope present at a level significantly above the natural abundance level of said isotope . such elevated or enriched levels of isotope are suitably at least 5 times , preferably at least 10 times , most preferably at least 20 times ; and ideally either at least 50 times the natural abundance level of the isotope in question , or present at a level where the level of enrichment of the isotope in question is 90 to 100 %. examples of such functional groups include ch 3 groups with elevated levels of 11 c , and fluoroalkyl groups with elevated levels of 18 f , such that the imaging moiety is the isotopically labelled 11 c or 18 f atom within the chemical structure . the radioisotopes 3 h and 14 c are not suitable imaging moieties . when the imaging moiety is a gamma - emitting radioactive halogen , the radiohalogen is suitably chosen from 123 i , 131 i or 77 br . a preferred gamma - emitting radioactive halogen is 123 i . when the imaging moiety is a positron - emitting radioactive non - metal , the imaging agent is suitable for positron emission tomography ( pet ). suitable such positron emitters include : 11 c , 13 n , 17 f , 18 f , 75 br , 76 br or 124 i . preferred positron - emitting radioactive non - metals are 11 c , 13 n , 124 i and 18 f , especially 11 c and 18 f , most especially 18 f . the imaging moiety is preferably a positron - emitting radioactive non - metal . the use of a pet imaging moiety has certain technical advantages , including : ( i ) the development of pet / ct cameras allowing easy co - registration of functional ( pet ) and anatomical ( ct ) images for improved diagnostic information ; ( ii ) the facility to quantify pet images to allow accurate assessment for staging and therapy monitoring ; ( iii ) increased sensitivity to allow visualisation of smaller target tissues . in one embodiment , the imaging agent comprises a synthetic compound of formula i : r 1 and r 2 are independently c 1 - 6 alkyl , or c 1 - 6 haloalkyl ; r 3a and r 3b are independently represent a bond , or a linker group selected from c 1 - 5 alkylene , — o —[ c 1 - 4 alkylene ]- or —[ c 1 - 2 alkylene ]- o —[ c 1 - 2 alkylene ]-; r 4 is selected from h , c 1 - 6 alkyl or c 1 - 6 alkoxy ; and , q a and q b are independently an a 3 group or -( a 2 ) n - r 5 ; wherein a 2 is selected from — o —, — och 2 —, — ch 2 o —, ch 2 , c ═ o , s ═ o , so 2 , — nh ( co )— or — co ( nh )—, r 5 is a phenyl group with 0 - 3 substituents which are a 3 groups , and n is an integer of value 0 to 3 ; wherein - a 3 is h , c 1 - 6 alkyl , oh or hal . r 1 and r 2 are independently selected from methyl , ethyl , 1 - methylethyl , r 3a and r 3b are independently c 1 - 3 alkylene or c 1 - 3 alkoxy ; q is 3 - phenoxy , 4 - phenoxy , 4 -( 3 - hydroxyphenoxy ), 4 -( 4 - methylphenyl ) sulfonyl , 4 -( 4 - chlorophenyl ) sulfonyl , 4 -( 2 , 4 - dichlorophenyl ) sulfonyl , 4 -( 4 - chlorophenoxy ), 4 - methylphenylamino , 4 - phenylamino , 4 - phenylthio , 4 - phenylsulfonyl , 4 - benzoyl , 4 -( 4 - iodophenoxy ), 3 -( 4 - iodophenoxy ), 4 -( 4 - fluorophenoxy ), 3 -( 4 - fluorophenoxy ), or 3 -( 4 - fluoroethyl ) phenoxy . preferred imaging agents which comprise compounds of formula i are of formula ia : im 1 and im 3 are independently h or an imaging moiety ; im 2 is c or the imaging moiety 11 c ; with the proviso that at least one of im 1 - 3 is an imaging moiety . im 1a and im 2a are independently h , hal , or an imaging moiety ; im 3a is c or the imaging moiety 11 c ; with the proviso that at least one of im 1 - 3 is an imaging moiety . in a further embodiment , the imaging agent comprises a synthetic compound of formula ii : r 6 is acyl , fluoroacyl or methylsulfonyl ; r 8 - r 9 are independently selected from h , c 1 - 3 alkyl , oh or hal . e is n or ch ; when e is n , x 1 is — ch 2 — and when e is ch , x 1 is — ch 2 — or — o —; ar 1 is a 6 - membered aryl ring having 0 - 2 n heteroatoms , and substituted with 0 to 3 r 7 groups ; each r 7 is independently chosen from c 1 - 3 alkyl , oh , hal , no 2 , nh 2 , co 2 h , c 1 - 6 alkoxy , c 1 - 6 amino , c 1 - 6 amido , — o ( ch 2 ch 2 o ) x x 2 or — nh ( ch 2 ch 2 o ) x x 2 where x is an integer of value 0 to 4 , and x 2 is h or ch 3 . in formula ii , r 6 is preferably acetyl ; r 8 - r 9 are preferably selected from h , ch 3 , oh , cl , f and i ; and ar 1 preferably comprises a phenyl or pyridine ring , most preferably a phenyl ring . preferably , the ar 1 ring is unsubstituted or substituted with one r 7 group . when present , r 7 is preferably chosen from : — oh , — nhch 3 , f , — o ( ch 2 ch 2 o ) x x 2 or — nh ( ch 2 ch 2 o ) x x 2 . x 2 is preferably h . preferred imaging agents which comprise compounds of formula ii are of formula iia : im 4 is independently h , ch 3 or an imaging moiety im 6 , im 7 and im 8 are independently h or an imaging moiety ; im 5 is c or the imaging moiety 11 c ; with the proviso that at least one of im 4 - 8 is an imaging moiety ; and , x 1 is as defined above for formula ii . wherein x 1 is as defined above for formula ii . in a further embodiment , the imaging agent comprises a synthetic compound of formula iii : r 10 is h or c 1 - 3 alkyl ; r 10a is ch 2 or a phenylene group with 0 - 2 substituents selected from c 1 - 3 alkyl , c 1 - 3 haloalkyl , or hal ; r 11 is h or a phenyl group with 0 - 3 substituents independently selected from oh , hal , c 1 - 6 alkyl , c 1 - 6 alkoxyalkyl , c 1 - 6 fluoroalkyl or nitrile ; r 11a is selected from ch , c 1 - 3 alkylene , and — o — c 1 - 3 alkylene ; r 12 is a phenyl group with 0 - 3 substituents selected from c 1 - 3 alkyl , c 1 - 3 haloalkyl , hal , c 1 - 3 alkylsulfonyl , or r 12 is — nhc ═ o — r x r y wherein : r x is selected from oxygen and ( ch 2 ) p wherein p is an integer of value 0 to 3 ; and , r y is a six - membered ring with 0 - 3 heteroatoms selected from o , n and s ; r 12a is h or oh ; r 13 is h , c 1 - 3 alkyl or a c 1 - 3 haloalkyl ; and , q c and q d are independently substituents selected from h , hal , c 1 - 3 alkyl , and c 1 - 3 alkyl sulfonyl . r 10 = h ; r 10a = ch 2 ; r 11 = 3 - fluorophenyl , 4 - fluorophenyl , 3 - chlorophenyl , 3 , 5 - difluorophenyl , 3 - fluoro , 4 - chloro - phenyl , 3 - hydroxy , 4 - iodophenyl , 4 - iodophenyl ; r 11a = ch ; r 12 = a phenyl group with 1 or 2 substituents selected from c 1 - 3 alkyl , c 1 - 3 haloalkyl , hal , c 1 - 3 alkylsulfonyl or r 12 is nhc ═ o — r x r y wherein : r x is oxygen ; and , r y is cyclohexyl , dihydropyran or tetrahydropyran ; r 12a = h ; r 13 = ethyl , fluoroethyl , propyl , or fluoropropyl ; and , q c is h and q d is 4 - c 1 - 3 alkyl or 4 - c 1 - 3 alkyl sulfonyl . r 10 = h or ch 3 ; r 10a = a phenylene group with a hal substituent ; r 11 = h ; r 11a = c 1 - 3 alkoxy ; r 12 = a phenyl group with 1 or 2 substituents selected from c 1 - 3 alkyl , c 1 - 3 haloalkyl , hal , c 1 - 3 alkylsulfonyl or r 12 is nhc ═ o — r x r y wherein : r x is oxygen ; and , r y is cyclohexyl , dihydropyran or tetrahydropyran ; r 12a = oh ; r 13 = ethyl , fluoroethyl , propyl , or fluoropropyl ; and , q c is h and q d is 4 - c 1 - 3 alkyl or 4 - c 1 - 3 alkyl sulfonyl . preferred imaging agents which comprise compounds of formula iii are of formulae iiia - iiic : im 9 and im 10 are independently h or an imaging moiety ; with the proviso that at least one of im 9 - 10 is an imaging moiety . im 11 and im 12 are independently h , ch 3 or an imaging moiety ; with the proviso that at least one of im 11 - 12 is an imaging moiety . im 12a - im 12d are independently h , ch 3 or an imaging moiety ; with the proviso that at least one of im 12a - im 12d is an imaging moiety . in a further embodiment , the imaging agent comprises a synthetic compound of formula iv : r 14 is h , c 1 - 6 alkyl , c 1 - 6 fluoroalkyl , c 1 - 6 alkoxy , or a phenyl or benzyl group optionally substituted with an a 4 group ; wherein a 4 is c 1 - 6 alkyl , c 1 - 6 alkoxy or hal ; r 14a is selected from hal or c 1 - 3 haloalkyl ; and , r 14b and r 14c are independently selected from ch 2 or n . preferred imaging agents which comprise compounds of formula iv are of formula iva or formula ivb : im 13 is independently ch 3 or an imaging moiety ; im 14 is independently c or the imaging moiety 11 c ; with the proviso that at least one of im 13 - 14 is an imaging moiety . im 14a is independently ch 3 or an imaging moiety ; im 14b is independently c or the imaging moiety 11 c ; with the proviso that at least one of im 14a - 14b is an imaging moiety . in a further embodiment , the imaging agent comprises a synthetic compound of formula v : r 15 and r 16 are independently h , oh , c 1 - 3 alkyl or hal ; and , r 15 and r 16 are independently h or hal ; and , r 17 is c 1 - 3 fluoroalkyl . preferred imaging agents which comprise compounds of formula v are of formula va : im 15 to im 17 are independently h or an imaging moiety ; with the proviso that at least one of im 15 - 17 is an imaging moiety . in a further embodiment , the imaging agent comprises a synthetic compound of formula vi : the synthetic compound having affinity for chemokine receptor 5 ( ccr5 ) can be obtained as follows : formula i — wo 00 / 06146 , shiraishi et al [ j . med . chem . 43 pp 2049 - 63 ( 2000 )]. formula ii — piperidine - 4 - carboxamide derivatives , imamura et al , [ bioorg . med . chem . 13 p . 397 - 416 ( 2005 ), and j . med . chem . 49 pp 2784 - 93 ( 2006 )]. formula iii — diphenylpropylpiperidine derivatives , cumming et al [ bioorg . med . chem . lett ., 16 p3533 - 3536 ( 2006 )], and shou - fu lu et al . bioorg . med . chem . lett ., 2007 , 17 , 1883 - 1887 . formula iv — piperazine - based derivatives , tagat et al [ j . med . chem ., 47 , 2405 - 8 ( 2004 )]. ; and tagat et al [ j . med . chem . 44 , 3343 - 6 ( 2001 )] formula vi — mitsuya et al [ j . med . chem . 49 pp 4140 - 52 ( 2006 ), and bioorg . med . chem . lett . 17 pp 727 - 31 ( 2007 )] the imaging agents of the first aspect are suitably prepared by reaction with a precursor , as described in the second aspect below . in a second aspect , the present invention provides a method for the preparation of the imaging agent of the first aspect , which comprises reaction of : ( i ) a non - radioactive precursor ; and , ( ii ) a suitable source of the imaging moiety of the first aspect , wherein said precursor is a derivative of the synthetic compound of the first aspect , and said derivative comprises a substituent y 1 which is capable of reaction with said suitable source of the imaging moiety to give the desired imaging agent . the “ precursor ” suitably comprises a non - radioactive derivative of the synthetic compound , which is designed so that chemical reaction with a convenient chemical form of the desired non - metallic radioisotope can be conducted in the minimum number of steps ( ideally a single step ), and without the need for significant purification ( ideally no further purification ) to give the desired radioactive product . such precursors are synthetic and can conveniently be obtained in good chemical purity . the “ precursor ” may optionally comprise a protecting group ( p gp ) for certain functional groups of the synthetic ccr5 compound . suitable precursors are described by bolton , j . lab . comp . radiopharm ., 45 , 485 - 528 ( 2002 ). by the term “ protecting group ” ( p gp ) is meant a group which inhibits or suppresses undesirable chemical reactions , but which is designed to be sufficiently reactive that it may be cleaved from the functional group in question under mild enough conditions that do not modify the rest of the molecule . after deprotection the desired product is obtained . protecting groups are well known to those skilled in the art and are suitably chosen from , for amine groups : boc ( where boc is tert - butyloxycarbonyl ), fmoc ( where fmoc is fluorenylmethoxycarbonyl ), trifluoroacetyl , allyloxycarbonyl , dde [ i . e . 1 -( 4 , 4 - dimethyl - 2 , 6 - dioxocyclohexylidene ) ethyl ] or npys ( i . e . 3 - nitro - 2 - pyridine sulfenyl ); and for carboxyl groups : methyl ester , tert - butyl ester or benzyl ester . for hydroxyl groups , suitable protecting groups are : methyl , ethyl or tert - butyl ; alkoxymethyl or alkoxyethyl ; benzyl ; acetyl ; benzoyl ; trityl ( trt ) or trialkylsilyl such as tert - butyldimethylsilyl . for thiol groups , suitable protecting groups are : trityl and 4 - methoxybenzyl . the use of further protecting groups are described in ‘ protective groups in organic synthesis ’, theorodora w . greene and peter g . m . wuts , ( third edition , john wiley & amp ; sons , 1999 ). preferred precursors are those wherein y 1 comprises a derivative which either undergoes direct electrophilic or nucleophilic halogenation ; undergoes facile alkylation with a labelled alkylating agent chosen from an alkyl or fluoroalkyl halide , tosylate , triflate ( i . e . trifluoromethanesulphonate ), mesylate , maleimide or a labelled n - haloacetyl moiety ; alkylates thiol moieties to form thioether linkages ; or undergoes condensation with a labelled active ester , aldehyde or ketone . examples of the first category are : ( a ) organometallic derivatives such as a trialkylstannane ( e . g . trimethylstannyl or tributylstannyl ), or a trialkylsilane ( e . g . trimethylsilyl ); ( b ) a non - radioactive alkyl iodide or alkyl bromide for halogen exchange and alkyl tosylate , mesylate or triflate for nucleophilic halogenation ; ( c ) aromatic rings activated towards electrophilic halogenation ( e . g . phenols ) and aromatic rings activated towards nucleophilic halogenation ( e . g . aryl iodonium , aryl diazonium , aryl trialkylammonium salts or nitroaryl derivatives ). preferred derivatives which undergo facile alkylation are alcohols , phenols , amine or thiol groups , especially thiols and sterically - unhindered primary or secondary amines . preferred derivatives which alkylate thiol - containing radioisotope reactants are maleimide derivatives or n - haloacetyl groups . preferred examples of the latter are n - chloroacetyl and n - bromoacetyl derivatives . preferred derivatives which undergo condensation with a labelled active ester moiety are amines , especially sterically - unhindered primary or secondary amines . preferred derivatives which undergo condensation with a labelled aldehyde or ketone are aminooxy and hydrazides groups , especially aminooxy derivatives . the “ precursor ” may optionally be supplied covalently attached to a solid support matrix . in that way , the desired imaging agent product forms in solution , whereas starting materials and impurities remain bound to the solid phase . precursors for solid phase electrophilic fluorination with 18 f - fluoride are described in wo 03 / 002489 . precursors for solid phase nucleophilic fluorination with 18 f - fluoride are described in wo 03 / 002157 . the solid support - bound precursor may therefore be provided as a kit cartridge which can be plugged into a suitably adapted automated synthesizer . the cartridge may contain , apart from the solid support - bound precursor , a column to remove unwanted fluoride ion , and an appropriate vessel connected so as to allow the reaction mixture to be evaporated and allow the product to be formulated as required . the reagents and solvents and other consumables required for the synthesis may also be included together with a compact disc carrying the software which allows the synthesiser to be operated in a way so as to meet the customer requirements for radioactive concentration , volumes , time of delivery etc . conveniently , all components of the kit are disposable to minimise the possibility of contamination between runs and will be sterile and quality assured . when the imaging moiety comprises a radioactive iodine isotope , y 1 suitably comprises : a non - radioactive precursor halogen atom such as an aryl iodide or bromide ( to permit radioiodine exchange ); an activated precursor aryl ring ( e . g . phenol or aniline groups ); an imidazole ring ; an indole ring ; an organometallic precursor compound ( e . g . trialkyltin or trialkylsilyl ); or an organic precursor such as triazenes or a good leaving group for nucleophilic substitution such as an iodonium salt . methods of introducing radioactive halogens ( including 123 i and 18 f ) are described by bolton [ j . lab . comp . radiopharm ., 45 , 485 - 528 ( 2002 )]. examples of suitable precursor aryl groups to which radioactive halogens , especially iodine can be attached are given below : both contain substituents which permit facile radioiodine substitution onto the aromatic ring . alternative substituents containing radioactive iodine can be synthesised by direct iodination via radiohalogen exchange , e . g . for radioactive isotopes of iodine , the radioiodine atom is preferably attached via a direct covalent bond to an aromatic ring such as a benzene ring , or a vinyl group since it is known that iodine atoms bound to saturated aliphatic systems are prone to in vivo metabolism and hence loss of the radioiodine . an iodine atom bound to an activated aryl ring like phenol has also , under certain circumstances , been observed to have limited in vivo stability . when the imaging moiety comprises a radioactive isotope of fluorine the radiofluorine atom may form part of a fluoroalkyl or fluoroalkoxy group , since alkyl fluorides are resistant to in vivo metabolism . for radioactive isotopes of fluorine ( e . g . 18 f ), the radiohalogenation may be carried out via direct labelling using the reaction of 18 f - fluoride with a suitable precursor having a good leaving group , such as an alkyl bromide , alkyl mesylate or alkyl tosylate . alternatively , the radiofluorine atom may be attached via a direct covalent bond to an aromatic ring such as a benzene ring . for such aryl systems , the precursor suitably comprises an activated nitroaryl ring , an aryl diazonium salt , or an aryl trialkylammonium salt . direct radiofluorination can , however , be detrimental to sensitive functional groups since these nucleophilic reactions are carried out with anhydrous [ 18 f ] fluoride ion in polar aprotic solvents under strong basic conditions . when the synthetic compound has alkali - sensitive functional groups , or other functionality unsuitable for direct radiohalogenation , an indirect radiohalogenation method is preferred . thus , when the imaging moiety comprises a radioactive halogen , such as 123 i and 18 f , y 1 preferably comprises a functional group that will react selectively with a radiolabelled synthon and thus upon conjugation gives the desired imaging agent product . by the term “ radiolabelled synthon ” is meant a small , synthetic organic molecule which is : ( i ) already radiolabelled such that the radiolabel is bound to the synthon in a stable manner ; ( ii ) comprises a functional group designed to react selectively and specifically with a corresponding functional group which is part of the desired compound to be radiolabelled . this approach gives better opportunities to generate imaging agents with improved in vivo stability of the radiolabel relative to direct radiolabelling approaches . a synthon approach also allows greater flexibility in the conditions used for the introduction of the imaging moiety . 18 f can also be introduced by n - alkylation of amine precursors with alkylating agent synthons such as 18 f ( ch 2 ) 3 oms ( where ms is mesylate ) to give n —( ch 2 ) 3 18 f , o - alkylation of hydroxyl groups with 18 f ( ch 2 ) 3 oms , 18 f ( ch 2 ) 3 ots or 18 f ( ch 2 ) 3 br or s - alkylation of thiol groups with 18 f ( ch 2 ) 3 oms or 18 f ( ch 2 ) 3 br . 18 f can also be introduced by alkylation of n - haloacetyl groups with a 18 f ( ch 2 ) 3 oh reactant , to give — nh ( co ) ch 2 o ( ch 2 ) 3 18 f derivatives or with a 18 f ( ch 2 ) 3 sh reactant , to give — nh ( co ) ch 2 s ( ch 2 ) 3 18 f derivatives . 18 f can also be introduced by reaction of maleimide - containing precursors with 18 f ( ch 2 ) 3 sh . for aryl systems , 18 f - fluoride nucleophilic displacement from an aryl diazonium salt , an aryl nitro compound or an aryl quaternary ammonium salt are suitable routes to aryl - 18 f labelled synthons useful for conjugation to precursors of the imaging agent . precursors wherein y 1 comprises a primary amine group can also be labelled with 18 f by reductive amination using 18 f — c 6 h 4 — cho as taught by kahn et al [ j . lab . comp . radiopharm . 45 , 1045 - 1053 ( 2002 )] and borch et al [ j . am . chem . soc . 93 , 2897 ( 1971 )]. this approach can also usefully be applied to aryl primary amines , such as compounds comprising phenyl - nh 2 or phenyl - ch 2 nh 2 groups . an especially preferred method for base - sensitive precursors is when y 1 comprises an aminooxy group of formula — nh ( c ═ o ) ch 2 — o — nh 2 which is condensed with 18 f — c 6 h 4 — cho under acidic conditions ( e . g . ph 2 to 4 ). further details of synthetic routes to 18 f - labelled derivatives are described by bolton , j . lab . comp . radiopharm ., 45 , 485 - 528 ( 2002 ). the precursor is preferably in sterile , apyrogenic form . methods for maintaining sterility are described in the third aspect below . examples of precursors suitable for the generation of imaging agents of the present invention are those where y 1 comprises an amine group which is condensed with the synthon n - succinimidyl 4 -[ 123 i ] iodobenzoate at ph 7 . 5 - 8 . 5 to give amide bond linked products . preferred precursors comprising the compounds of formula i to formula v are of formula ip to vp respectively : wherein at least one of e 1 - e 4 and y a - y b comprises y 1 , and the remaining e 1 - e 4 and y a - y b groups are r 1 - r 4 and q a - q b groups respectively of formula i . wherein at least one of e 6 - e 9 comprises y 1 , and the remaining e 6 - e 9 groups are r 6 - r 9 groups respectively of formula ii . wherein at least one of e 10 , e 11 , e 12 , or e 13 comprises y 1 and the remaining e 10 , e 11 , e 12 , or e 13 groups are r 10 - r 13 groups respectively of formula iii ; e 11a - e 12a are as defined for e 11a - e 12a of formula iii ; and , y c and y d are as defined for q c and q d of formula iii . wherein e 14 is an r 14 group of formula iv which comprises y 1 ; and , e 14a - e 14c are as defined for r 14a - r 14c of formula iv . wherein at least one of e 15 - e 17 comprises y 1 and the remaining e 15 - e 11 groups are r 15 - r 17 respectively of formula v . wherein at least one of e 18 - e 20 comprises y 1 and the remaining e 18 - e 20 groups are r 18 - r 20 respectively of formula vi ; and , in a third aspect , the present invention provides a pharmaceutical composition which comprises the imaging agent of the first aspect together with a biocompatible carrier , in a form suitable for mammalian administration . the “ biocompatible carrier ” is a fluid , especially a liquid , in which the imaging agent can be suspended or dissolved , such that the composition is physiologically tolerable , i . e . can be administered to the mammalian body without toxicity or undue discomfort . the biocompatible carrier is suitably an injectable carrier liquid such as sterile , pyrogen - free water for injection ; an aqueous solution such as saline ( which may advantageously be balanced so that the final product for injection is isotonic ); an aqueous solution of one or more tonicity - adjusting substances ( e . g . salts of plasma cations with biocompatible counterions ), sugars ( e . g . glucose or sucrose ), sugar alcohols ( e . g . sorbitol or mannitol ), glycols ( e . g . glycerol ), or other non - ionic polyol materials ( e . g . polyethyleneglycols , propylene glycols and the like ). preferably the biocompatible carrier is pyrogen - free water for injection or isotonic saline . such radioactive pharmaceutical compositions ( i . e . radiopharmaceutical compositions ) are suitably supplied in either a container which is provided with a seal which is suitable for single or multiple puncturing with a hypodermic needle ( e . g . a crimped - on septum seal closure ) whilst maintaining sterile integrity . such containers may contain single or multiple patient doses . preferred multiple dose containers comprise a single bulk vial ( e . g . of 10 to 30 cm 3 volume ) which contains multiple patient doses , whereby single patient doses can thus be withdrawn into clinical grade syringes at various time intervals during the viable lifetime of the preparation to suit the clinical situation . pre - filled syringes are designed to contain a single human dose , or “ unit dose ” and are therefore preferably a disposable or other syringe suitable for clinical use . the pre - filled syringe may optionally be provided with a syringe shield to protect the operator from radioactive dose . suitable such radiopharmaceutical syringe shields are known in the art and preferably comprise either lead or tungsten . the radiopharmaceutical compositions may be prepared from kits , as is described in the fourth aspect below . alternatively , the radiopharmaceuticals may be prepared under aseptic manufacture conditions to give the desired sterile product . the radiopharmaceuticals may also be prepared under non - sterile conditions , followed by terminal sterilisation using e . g . gamma - irradiation , autoclaving , dry heat or chemical treatment ( e . g . with ethylene oxide ). in a fourth aspect , the present invention provides a kit for the preparation of the pharmaceutical composition of the third aspect , which kit comprises the precursor of the second aspect . such kits comprise the “ precursor ” of the second aspect , preferably in sterile non - pyrogenic form , so that reaction with a sterile source of the radioisotopic imaging moiety gives the desired radiopharmaceutical with the minimum number of manipulations . such considerations are particularly important when the radioisotope has a relatively short half - life , and for ease of handling and hence reduced radiation dose for the radiopharmacist . hence , the reaction medium for reconstitution of such kits is preferably a “ biocompatible carrier ” as defined above , and is most preferably aqueous . suitable kit containers comprise a sealed container which permits maintenance of sterile integrity and / or radioactive safety , plus optionally an inert headspace gas ( e . g . nitrogen or argon ), whilst permitting addition and withdrawal of solutions by syringe . a preferred such container is a septum - sealed vial , wherein the gas - tight closure is crimped on with an overseal ( typically of aluminium ). such containers have the additional advantage that the closure can withstand vacuum if desired e . g . to change the headspace gas or degas solutions . the non - radioactive kits may optionally further comprise additional components such as a radioprotectant , antimicrobial preservative , ph - adjusting agent or filler . by the term “ radioprotectant ” is meant a compound which inhibits degradation reactions , such as redox processes , by trapping highly - reactive free radicals , such as oxygen - containing free radicals arising from the radiolysis of water . the radioprotectants of the present invention are suitably chosen from : ascorbic acid , para - aminobenzoic acid ( i . e . 4 - aminobenzoic acid ), gentisic acid ( i . e . 2 , 5 - dihydroxybenzoic acid ) and salts thereof with a biocompatible cation . by the term “ biocompatible cation ” is meant a positively charged counterion which forms a salt with an ionised , negatively charged group , where said positively charged counterion is also non - toxic and hence suitable for administration to the mammalian body , especially the human body . examples of suitable biocompatible cations include : the alkali metals sodium or potassium ; the alkaline earth metals calcium and magnesium ; and the ammonium ion . preferred biocompatible cations are sodium and potassium , most preferably sodium . by the term “ antimicrobial preservative ” is meant an agent which inhibits the growth of potentially harmful micro - organisms such as bacteria , yeasts or moulds . the antimicrobial preservative may also exhibit some bactericidal properties , depending on the dose . the main role of the antimicrobial preservative ( s ) of the present invention is to inhibit the growth of any such micro - organism in the radiopharmaceutical composition post - reconstitution , i . e . in the radioactive diagnostic product itself . the antimicrobial preservative may , however , also optionally be used to inhibit the growth of potentially harmful micro - organisms in one or more components of the non - radioactive kit of the present invention prior to reconstitution . suitable antimicrobial preservative ( s ) include : the parabens , i . e . methyl , ethyl , propyl or butyl paraben or mixtures thereof ; benzyl alcohol ; phenol ; cresol ; cetrimide and thiomersal . preferred antimicrobial preservative ( s ) are the parabens . the term “ ph - adjusting agent ” means a compound or mixture of compounds useful to ensure that the ph of the reconstituted kit is within acceptable limits ( approximately ph 4 . 0 to 10 . 5 ) for human or mammalian administration . suitable such ph - adjusting agents include pharmaceutically acceptable buffers , such as tricine , phosphate or tris [ i . e . tris ( hydroxymethyl ) aminomethane ], and pharmaceutically acceptable bases such as sodium carbonate , sodium bicarbonate or mixtures thereof . when the conjugate is employed in acid salt form , the ph adjusting agent may optionally be provided in a separate vial or container , so that the user of the kit can adjust the ph as part of a multi - step procedure . by the term “ filler ” is meant a pharmaceutically acceptable bulking agent which may facilitate material handling during production and lyophilisation . suitable fillers include inorganic salts such as sodium chloride , and water soluble sugars or sugar alcohols such as sucrose , maltose , mannitol or trehalose . preferred aspects of the “ precursor ” when employed in the kit are as described for the second aspect above . the precursors for use in the kit may be employed under aseptic manufacture conditions to give the desired sterile , non - pyrogenic material . the precursors may also be employed under non - sterile conditions , followed by terminal sterilisation using e . g . gamma - irradiation , autoclaving , dry heat or chemical treatment ( e . g . with ethylene oxide ). preferably , the precursors are employed in sterile , non - pyrogenic form . most preferably the sterile , non - pyrogenic precursors are employed in the sealed container as described above . in a fifth aspect , the present invention provides a method for the in vivo diagnosis or imaging in a subject of a ccr5 condition , comprising administration of the pharmaceutical composition of the third aspect . by the term “ ccr5 condition ” is meant a disease state of the mammalian , especially human , body where ccr5 expression is upregulated or downregulated . preferably , the ccr5 expression is upregulated since that should give better signal - to - background in diagnostic imaging in vivo . ccr5 expression is upregulated in chronic hiv infection . ccr5 conditions also include various pathological inflammatory conditions as well as neuroinflammatory conditions . pathological inflammatory conditions include : atherosclerosis , chronic obstructive pulmonary disorder ( copd ), rheumatoid arthritis , osteoarthritis , allergic disease , hiv / aids , asthma and cancer . neuroinflammatory conditions include : multiple sclerosis ( ms ), alzheimer &# 39 ; s disease ( ad ) and parkinson &# 39 ; s disease ( pd ). a preferred method of the fifth aspect is the in vivo diagnosis or imaging of neuroinflammation . most neurodegenerative diseases have an element of inflammation . in a sixth aspect , the present invention provides the use of the pharmaceutical composition of the third aspect for imaging in vivo in a subject a ccr5 condition wherein said subject is previously administered with said pharmaceutical composition . the “ ccr5 condition ” and preferred embodiments thereof are as defined for the fifth aspect , above . by “ previously administered ” is meant that the step involving the clinician , wherein the imaging agent composition is given to the patient e . g . intravenous injection , has already been carried out . in a seventh aspect , the present invention provides the use of the imaging agent of any one of the first aspect for the manufacture of a pharmaceutical for use in a method for the diagnosis of a ccr5 condition . the “ ccr5 condition ” and preferred embodiments thereof are as defined for the fifth aspect , above . in an eighth aspect , the present invention provides a method of monitoring the effect of treatment of a human or animal body with a drug to combat a ccr5 condition , said method comprising administering to said body the pharmaceutical composition of the third aspect , and detecting the uptake of the imaging agent of said pharmaceutical composition . the “ ccr5 condition ” and preferred embodiments thereof are as defined for the fifth aspect , above . in a ninth aspect , the present invention provides the pharmaceutical composition of the invention for use in a method for the diagnosis of a ccr5 condition . the “ ccr5 condition ” and preferred embodiments thereof are as defined for the fifth aspect , above . example 1 provides the synthesis of a non - radioactive 19 f counterpart compound falling within formula i of the present invention (“ compound 1 ”). since the 18 f version differs only in the fluorine isotope , it is chemically almost identical . example 2 provides the synthesis of a non - radioactive 19 f counterpart compound falling within formula ii of the present invention (“ compound 8 ”). since the 18 f version differs only in the fluorine isotope , it is chemically almost identical . examples 3 and 4 provide prophetic examples of the syntheses of 18 f - labelled compounds 1 and 8 . example 5 provides a prophetic example of the syntheses of an 18 f - labelled compound of formula v . example 6 provides biological screening data for compound 8 of example 2 . this shows that compound 8 binds ccr5 with high affinity and is selective for ccr5 as it does not bind ccr1 and ccr2b . example 7 provides the screening of compounds 1 and 8 in a membrane permeability assay ( pampa assay ). pe ( permeability ) predict a high cns ( blood brain barrier ) permeability for compound 8 and intermediate permeability for compound 1 . a solution of 5 - amino - 2 - methoxyphenol ( 2 . 78 g , 0 . 020 mol ), 4 - phenoxybenzoic acid ( 4 . 28 g , 0 . 020 mol ), diea ( 3 . 1 g , 4 . 2 ml , 0 . 024 mol ) and hobt ( 3 . 2 g , 0 . 024 mol ) in dmf ( 20 ml ) was cooled to 0 ° c ., edcl ( 4 . 6 g , 0 . 024 mol ) was added in one portion under nitrogen . the mixture was stirred at room temperature overnight . the mixture was poured into ice - water ( 100 ml ) and extracted with ethyl acetate ( 50 ml × 3 ). the combined ethyl acetate layer was washed with water , brine , dried ( mgso 4 ) and concentrated to dryness . the residue solid was triturated with dcm / hexanes , affording a white solid ( 4 . 1 g , 62 %). 1 h nmr and lcms analysis indicated & gt ; 98 % purity . the required intermediate 2 -( ethyl - 2 ′- fluoroethylamino ) ethanol was prepared as shown in scheme 2 . a mixture of 2 - ethylaminoethanol ( 6 . 7 g , 0 . 075 mol ), 2 - fluoroethyl bromide ( 12 g , 0 . 094 mol ), anhydrous potassium carbonate ( 10 . 3 g , 0 . 075 mol ) and dry benzene ( 50 ml ) was heated under reflux with stirring for 48 h . after cooling to room temperature , the solid was removed by filtration and washed with benzene . the benzene was removed in vacuo . nmr analysis indicated the purity of the product was − 90 % and it was used directly in the next step without any further purification . ( 9 . 0 g , 89 %). diad ( 1 . 36 g , 1 . 3 ml , 6 . 71 mmol ) was added dropwise to a solution of compound a from step ( i ) ( 1 . 50 g , 4 . 47 mmol ), 2 -( ethyl - 2 ′- fluoroethylamino ) ethanol from step ( ii ) ( 0 . 91 g , 6 . 71 mmol ) and pph 3 ( 1 . 76 g , 6 . 71 mmol ) in anhydrous dcm (/ thf ( 12 ml , 5 : 1 ). an exothermic reaction was immediately observed . the mixture was then stirred at room temperature overnight . the reaction mixture was concentrated to dryness and the residue solid was purified by column chromatography [ silica , dcm → dcm / meoh ( 98 : 2 )]. the second fraction was the desired product , this fraction was chromatographed again under the same condition stated above . recrystallisation from dcm / hexanes afforded a colourless solid ( 0 . 81 g , 40 %). analytical data indicated & gt ; 98 % purity . lcms ( api - es + ) m / z 453 . 3 ( m + h + ) supporting data : 1 h nmr , 13 c nmr , hplc , lcms of compound 1 . ethylpiperidine - 4 - carboxylate ( 10 g , 0 . 064 mol , 1 . 1 eq ) and triethylamine ( 15 ml , 2 eq ) were dissolved in dcm ( 30 ml ), and cooled on ice water bath with magnetic stirring . 2 - fluoroacetylchloride ( 5 g , 0 . 052 mol , 1 . 0 eq ) in dcm ( 20 ml ) was added dropwise ( 15 min ) to the reaction and stirred for 1 h . water ( 100 ml ) was added and solvent was removed in vacuo . the residue was extracted into ethyl acetate ( 300 ml ), which was washed with water , 2n hcl , saturated nahco 3 , brine and dried over mg 2 so 4 . the organic solution was filtered , then concentrated . after silica gel column chromatography 6 . 2 g ( yield 55 %) of product compound 5 was obtained . compound 5 ( 6 . 2 g , 0 . 029 mol , 1 eq ) was dissolved in methanol ( 100 ml ) and 2n naoh ( 30 ml , 2 eq ) was added and stirred overnight . the methanol was then removed in vacuo . the residue was acidified with 2n hcl to ph 3 , extracted with ethyl acetate ( 3 × 500 ml ), dried over mgso 4 , filtered and concentrated to afford compound 6 ( 4 . 3 g , yield 78 %). compound 6 ( 4 . 3 g , 0 . 023 mol ) dissolved in dcm ( 50 ml ), and dmf ( one drop ) was added , cooled on ice water bath , followed by addition of oxalyl dichloride ( 2 . 3 g , 1 . 5 ml , 2 . 5 eq ) and stirred for 2 h . solvent was removed and dry toluene ( 50 ml ) was added to chase out possible residual solvent on a 50 ° c . water bath to give compound 7 ( 4 . 2 g , yield 88 %). 3 - chloro - 4 - methylbenzenamine ( 15 g , 0 . 106 mol , 1 eq ), 2 -( ethoxycarbonyl )- acetic acid ( 14 g , 0 . 106 mol , 1 eq ), diisopropylethylamine ( 16 . 5 g , 22 . 3 ml , 1 . 2 eq ), hobt ( 17 g , 1 . 2 eq ) and dcm ( 150 ml ) were mixed together . [ 1 - ethyl -( 3 - dimethyl - amino - propyl ) carbodiimide hydrochloride anhydrous ] ( edcl , 24 . 5 g , 1 . 2 eq ) was then added , and the resulting mixture stirred overnight under n2 . workup , the reaction mixture washed with water , saturated nahco 3 , 1n hcl and brine , dried over mgso 4 . filtered off and concentrated to afford compound 1 ( 18 . 5 g , yield 70 %). compound 1 from step ( iv ) above ( 18 . 5 g , ˜ 0 . 072 mol ) was dissolved in methanol ( 100 ml ), and cooled on an ice water bath . 2n naoh ( 72 ml , 2 eq ) was added and the mixture stirred overnight . then solvent methanol was removed in vacuo . the residue was acidified with 2n hcl to ph 2 and extracted with ethyl acetate ( 500 ml ), dried over mgso 4 , filtered off and concentrated to give compound 2 ( 13 g , 80 %). compound 2 from step ( v ) ( 4 . 9 g , ˜ 0 . 021 mol ), 4 - fluorobenzylpiperidine hydrochloride ( 4 . 9 g , 0 . 021 mol ), diisopropylethylamine ( 12 g , 2 . 2 eq ), hobt ( 3 . 5 g , 1 . 2 eq ) and dmf ( 150 ml ) were mixed together . [ 1 - ethyl -( 3 - dimethyl - aminopropyl ) carbodiimide hydrochloride anhydrous ] ( edcl , 5 g , 1 . 2 eq ) was then added . the resulting mixture was stirred overnight under n2 . workup , the reaction mixture was diluted with water ( 800 ml ), extracted with ethyl acetate ( 500 ml ), washed with water , saturated nahco 3 , 1n hcl and brine , dried over mgso 4 . filtered off and concentrated to afford compound 3 ( 6 . 8 g , yield 80 %). compound 3 from step ( v ) ( 6 . 8 g , 0 . 017 mol ) was dissolved in thf ( 100 ml ), and bh 3 ( 1m solution in thf , 170 ml , 10 eq ) was added and refluxed for 4 days till reaction complete ( checked with lcms ). solvent thf was then removed and methanol ( 100 ml ) 6n hcl ( 100 ml ) was added and refluxed for 5 days till reaction complete ( checked with lcms ). then methanol was removed and the residue was acidified to ph 11 . extracted with dcm ( 500 ml ), dried over mgso 4 , filtered off and concentrated ( crude 6 . 2 g ). after silica gel column give compound 4 ( 3 . 7 g , 58 %). compound 4 from step ( vi ) ( 2 . 5 g , 0 . 0067 mol ) and triethylamine ( 7 g , 10 ml , 0 . 068 mol , eq ) was dissolved in dcm ( 50 ml ), cooled on ice water bath , added compound 7 ( 4 . 2 g , ˜ 3 eq ) in dcm ( 50 ml ). the resulting mixture was stirred overnight . reaction is messy but lcms showed the desired product molecular weight . workup , water was added , solvent dcm was removed in vacuo . residue was extracted with ethyl acetate ( 500 ml ), washed with water , saturated nahco 3 , dried over mgso 4 , filtered off and concentrated , after silica gel column chromatography give final compound 8 ( 179 mg , 5 %). lcms ( api - es + ) m / z 546 . 3 ( m + h + ). 18 f - labelled compound 1 is prepared as shown in scheme 5 : the f - 18 analogue of compound 8 is synthesized from compound 4 of example 2 as shown in scheme 6 : an 18 f - labelled compound of formula v is prepared as shown in scheme 7 : compound 8 of example 2 was screened in ccr binding assays as follows : the ccr1 binding assay was performed under the following conditions , according to a method that was adapted from the literature [ ben - baruch et al ., j . biol . chem ., 270 ( 38 ), 22123 - 8 ( 1995 ); pease et al ., j . biol . chem ., 273 ( 32 ), 19972 - 6 ( 1998 )]. thus , compound 8 was incubated for 3 hours at 25 ° c . in 50 mm hepes , ph7 . 4 containing 1 mm cacl 2 , 0 . 5 % bsa , 5 mm mgcl 2 and 1 % dmso with human recombinant cho - k1 cells in the presence of 0 . 02 nm [ 125 i ]- mip - 1α . mip - 1α is macrophage inflammatory protein 1α ( ligand of ccr1 and ccr5 ). ccr2b binding assay was performed under the following conditions , according to a method that was adapted from the literature [ gong et al ., j . biol . chem ., 272 , 11682 - 5 ( 1997 ); moore et al ., j . leukoc . biol ., 62 , 911 - 5 ( 1997 )]. thus , compound 8 was incubated for 1 hour at 25 ° c . in 25 mm hepes , ph7 . 4 containing 1 mm cacl 2 , 0 . 5 % bsa , 5 mm mgcl 2 , 0 . 1 % nan 3 and 1 % dmso with human recombinant cho - k1 cells in the presence of 0 . 1 nm [ 125 i ]- mcp - 1 . mcp - 1 is monocyte chemoattractant protein ( the ligand of ccr2 ). ccr5 binding assay was performed under the following conditions , according to a method that was adapted from the literature [ samson et al ., j . biol . chem ., 272 , 24934 - 41 ( 1997 )]. thus , compound 8 was incubated for 2 hours at 25 ° c . in 50 mm hepes , ph7 . 4 containing 1 mm cacl 2 , 0 . 5 % bsa , 5 mm mgcl 2 and 1 % dmso with human recombinant cho - k1 cells in the presence of 0 . 1 nm [ 125 i ]- mip - 1β , where mip - 1β is macrophage inflammatory protein 1β . compound 8 was found to be selective for ccr5 ( ki 0 . 79 nm ) since binding affinity for ccr1 was much lower ( 32 % binding inhibition at 10 μm compound 8 ) and compound 8 at 10 μm concentration did not inhibit the binding of mcp - 1 to ccr2b . the permeability of the ccr compounds was measured in a parallel artificial membrane permeability assay ( pampa ) which gives a prediction of the blood brain barrier penetration by passive diffusion [ di et al , eur . j . med . chem ., 38 ( 3 ), 223 - 232 ( 2003 )]. the commonly accepted classification ranges for this pampa assay are as follows : high predicted passive bbb permeation : pe & gt ; 4 . 0 × 10 − 06 cm / sec . low predicted passive bbb permeation : pe & lt ; 2 . 0 × 10 − 06 cm / sec . the results were pe = 3 . 2e - 06 cm / sec for compound 1 and pe = 6 . 8e - 06 cm / sec for compound 8 .
the present invention relates to the field of medical imaging , and in particular to imaging of disease states associated with the upregulation of the chemokine receptor 5 . imaging agents , precursors and methods are provided which are useful in imaging such disease states .