3+ 1 NM R. Ju risson [ 2 ] [ 3. ( ) (B ifunc2 20, 18 F N 4, O 4, S4, O 4- nsn, N 4- no n, P 4 N 4- nsn. V o l. 15 N o. 4 N ov.
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1 Journal of Iso topes V o l. 15 N o. 4 N ov Tc m 3+ 1, (, ) : 3+ 1, 99 T c m 3+ 1, : 99 T c m ; 3+ 1 ; : R 817; R : A : (2002) , CT M R I Johann sen NM R 3+ 1, Ju risson [ 2 ] [ 3 ] 99 T c m 99 T c m,, 3+ 1 ( ) (B ifunc2 tional Chelate,BFC) 99 T c m 3+ 1, [ 1 ], 20, 18 F 123 I 11 C, 1 99 Tc m 3+ 1, 99 T c m O 4 -,, 99 T c m (, h 140 kev ) SPECT ; 99 M o2 99 T c m, 99 T c m, ; 99 T c m 99 T c m, T co 3+ N 4, O 4, S4,, O 4- nsn, N 4- no n, P 4 N 4- nsn 99 T c m,, : ; : : (1977 ), ( ),,,
2 220 15, BFC;,,,,, 99 T c m BFC 99 T c m, 3+ 1 : 99 T c m (Con jugate A pp roach ) ( In te grated A pp roach) BFC, BFC BFC 4 : (,, H YN IC) N x S4- x T c (CO ) 3+,,, 2 99 Tc m 3+ 1 [ 4 ] ; T c (CO ) 3+, ; 99 T c m 3+ 1 [ 5 ], N x S4- x N 2S2,,, N a 99 T c m O 4,, SnC l2, 3+ 1 N a2s2o 4, 3+ 1 (N agh ) (N a2gluconate) ON S ONO SO S SNN S 99 T c m SSS T co 3+ T col +,, (1), (1) L 1,L 2 N at co 4+ N agh T co GH,,, (L 1, L 2) SN S SSS, T co (L 1,L 2) (1) [ 6 ], L 1,, 99 T c H S, 3+ CH 2CH 2SCH 2CH 2 SH H S CH 2CH 2OCH 2CH 2 1, SH H S CH 2CH 2N (R ) CH 2CH 2 SH, 3+ 1 M OL 1L 2 L 2 ; L 2, L 1, : M O SN SgS M O SNN gs (M = T c R e), Seifert [ 10 ], 99 T c m M O SN SgS M O SNN gs 3+ 1, N R, R O,, [ 7 ] M O SO SgS M O SSSgS [ 8 ],,, 3+ 1, [ 9 ], T c (OC l4) -,, 3+ 1,
3 4 : 99 T c m , Johann sen, 99 T c m 3 [ 9, 11 ] , 2, A 1 A 2 Johann sen 3+ 1, (2), (2) 52H T 2A, L 1,L 2, A 2 A 3, 90% N at co 4+ N agh L 1 [T co (L 1) 4 ) - L 2 T co GH [T col 1L 2 ] (2) N N A 3 p K a, ph, A 3 A 4, N 3 99 Tc m 3+ 1 p K a,, T c m 3+ 1 [ 12 ], 52 (52hydroxytrypa2 52H T 2A, K i= m ine, 52H T ) (Dopam ine, DA ) 10-9 m o l L - 1, (Dopam ine T ran spo rter, 52H T 1A DA T ), W A Y L eon [ 13 ] W A Y ( 22 ) H T 52H T (M PP) 3+ 1, 52H T 3 B 1 B 2, 52H T 52H T 1A ( IC 50 15, Ketan serin 52H T 2A 67 nm o l L nm o l L - 1 ), (42 ) Tc m 3+ 1 Ketan ser in IC 50gnmo l L - 1 A 1 > A 2 > m in g% ID pk a 1 5-HT2A Ketan ser in A 3 > A Re 99 Tc m Ketan ser in
4 222 15, Ka tzenellen2 (BBB ), 1 m in 1. 4 bogen [ 17 ], 0. 9% ID g,, 60 m in 1. 7 [ 14 ], W u st [ 18, 19 ] 52H T 1A (B 1),, 3+ 1,,, 4 52H T 1A, C 1,, (180 m in) ( testo sterone) (C 2), SPECT, 52H T 1A Skaddan [ 20, 21 ] 7Α Papagiannopou lou [ 6 ], 99 T c m 3+, 12(22 ) 1,, 99 T c m % 45% 99 T c, 3 B 3 B 5 B 3 B 4 B 5 BBB ( 1 m in % ID ), B 4 B 5, (DA T ) 52H T 1A, ( IC 50= 6 31 nm o l L - 1 ) DA, [ 15 B 6 ], DA T Cocaine W IN (E stro2 DA T, 99 T c m 2TRODA T gen ) (A ndrogen), 21 [ 22 ] M eegalla [ 23 ] W IN [ 16 ], (P rogesterone), 99 T c m Benztrop ine N 2S2 N 99 T c m, 3 65%, T c m 2IPT, 5 99,, T c m 2IPT DA T, K i 99 T c m m o l L - 1, 3 99 Tc m W AY
5 4 : 99 T c m Re Tc m - IPT 6 Re-SSS-S-Α-Tropanol 7 99 Tc m 3+ 1 Benztrop ine Johann sen [ 24 ] Benztrop ine 3Α DA T, D 2, 3+ 1 Benztrop ine [ 27,, ] (Su lp iride),, IC 50 ( > 10 Λm o l 5 ( ) L - 1 ), ( 6) (S ) 2(- ) 252 2N 2[ ( ) IC 50 Johann sen Ben2 ]222 M BZM ztrop ine Ketan serin 3+ 1 D 2, 3Α 99 T c m 2M BZM [ 25 ], 99 T c m 2M BZM, 2 99 T c m 3+ 1 Benztrop ine, m in % ID g 7, ,,, Am artey [ 28 ] ( 2 99 Tc m 3+ 1 F1 F2 )RC2160, m in g% ID g g F F 1 ( ) F [ 26 ] 3+ 1, H TB 2121, RC , F riebe [ 29 ] 3+ 1
6 224 15,, H 3, H 3 8 B 16 H 2,, 60 m in 60 m in 40% 69% ; H 3 F 2, 60 m in, 5% ID g, (4. 3) , T soukalas [ 33 ], SNN gs SN SgS, 99 T c T c m 2ECD,,, [ 34, 35, ], M astro stam atis [ 30 ] 99 T c m 2 GH, T co 3+, 3,, + 1, %,, H 1 H 2,, % ID,, [ 32 ], 3+ 1, M iao Yub in [ 36, 37 ] 30 m in, N 2(22 ) 21, 22 (M PBDA ) [ 31 ], T c m 2 M PBDA 99 T c m 2M PBDA,, 2 m in 1. 85% ID, 1. 64% ID; 1 h 8 99 Tc m m in : 63. 2%, 76. 8%, , 9 99 Tc m Tc m -M TPGA
7 4 : 99 T c m m in 2. 12% ID, 4. 70% ID; 1 h 2 m in 83%, 99 T c m 2ECD [ 38 ],, Tc m T c m Kneiss [ 41 ], 99 T c m 3+ 1, 12, m o l L - 1 N ock [ 39 ] ( N H 2) ( NO 2) 4 99 Tc m ,,, R, : NO 2> > H > N H 2,, , [ 40, ] 99 T c m 3+ 1, 3 99 T c m,, , ph 5 7, 99 T c m m in, 90% ; 1, 99 T c m ,, J 2 J 3 99 T c m 3+ 1, 3+ 1 Seifert, BFC Tc m 3+ 1 : 3 99 Tc m 3+ 1,, 1 ; g% ID g-, ; 5 m in 30 m in 5 m in 30 m in J J J J [ 42 ], 3+ 1, ,, 3+ 1,, 3+ 1,, BFC ( ), 3+ 1 BFC, :,, ;
8 226 15,, [7 ] Papadopoulo sm S, Pelecanou M, P irm ettis IC, et BFC al. A N ew Dono r A tom System [ (SNN ) (S) ] fo r, the Syn thesis of N eu tral O xo technetium ( V ) M ixed2l igand Comp lexes[j ]. Ino rg Chem, 1996,, Syh re [ 43 ] 35 (15): [8 ] P irm ettis IC, Papadopoulo s M S, M astro stam atis, SG, et al. Syn thesis and Characterization of O x2, 3+ 1 o technetium (V ) M ixed2l igand Comp lexes Con2 taining a T ridentate N 2Substituted B is (22m ercap2 toethyl) am ine and a M onodentate T h io l[j ]. In2 3+ 1, o rg Chem, 1996, 35 (6): [ 9 ] Johannsen B, Scheunem ann M, Sp ies H, et al. 3+ 1, 3+ T echnetium (V ) and R henium (V ) Comp lexes fo r 1 52H T 2A Sero tonin R ecep to r B inding: Structure2 [ 44 ], affin ity Con sideration s[j ]. N uclm ed B io l, 1996, 23: , [10 ] Seifert S, P ietzsch H 2J, Scheunem ann M, et al., 3+ 1 N o Carrier A dded P reparation of 3+ 1 M ixed2 ligand 99 T c m Comp lexes [J ]. A pp l R adiat Iso t, 1998, 49 (2): [ 11 ] Johannsen B, Berger R, B rust P, et al. Struc2 : tural M odification of R ecep to r 2B inding T ech2 [ 1 ]. [J ]. netium 299m Com p lexes in O rder to Im p rove, 1997, 17 (4): 197. B rain U p take [J ]. Eur J N ucl M ed, 1997, 24: [ 2 ] Jurisson SS, John DL. Po tential T echnetium Sm allm o lecu le R adiopharm aceu ticals[j ]. Chem [ 12 ] P ietzsch HJ, Scheunem ann M, K retzschm ar M, R ev, 1999, 99: et al. Syn thesis and A u to radiograph ic Evaluation [ 3 ],. 99 T c m of a N ovel H igh2affinity T c299m L igand fo r the [J ]., 2001, 52H T 2A R ecep to r[j ]. N uclm ed B io l, 1999, 26: 14: [4 ] H irsch KM, N icho lson T, D avison A, et al. Syn2 thesis and Characterization of R henium (g ) and T echnetium ( g ) O rganohydrazide Chelate Com 2 p lexeṡ R eaction s of 22H ydrazinopyridine W ith Comp lexes of R henium and T echnetium [J ]. Chem, 1997, 36 (15): Ino rg [5 ] Sch ibli R, Karra SR, Katti KV, et al. In V itro and in V ivo Characterization of a N ovel B ifunc2 tion lized W ater2so lub le D ith ia2b ispho sph ine 99 T c m 2comp lex [J ]. R adioch im A cta, 1998, 83: [ 6 ] Papagiannopoulou D, P irm ettis I, M aina T, et al. D evelopm ent of N ovelm ixed2ligand O xo tech2 netium [SN SgS ] Comp lexes as Po tential 52H T 1A R ecep to r Im aging A gents [ J ]. J B io l Ino rg Chem, 2001, 6 (3): [ 13 ] L eon A, R ey A, M allo L, et al. N ovel M ixed L igand T echnetium Com p lexes as 52H T 1A R e2 cep to r Im aging A gents [ J ]. N ucl M ed B io l, 2002, 29 (2): [14 ],,,. 99 T c m WA Y 52H T 1A [A ]. [C ]. :, [ 15 ],,. 52 WA Y [J ]., 2001, 14 (1): [ 16 ] Katzenellenbogen BS, Katzenellenbogen JA. E s2 trogen R ecep to r T ranscrip tion and T ransactiva2 tion: E strogen R ecep to r A lpha and E strogen R e2 cep to r Beta: R egu lation by Selective E strogen
9 4 : 99 T c m R ecep to r M odulato rs and Impo rtance in B reast Cancer[J ]. B reast Cancer R es, 2000, 2 (5): [17 ] Katzenellenbogen JA, Co lem an R E, H aw k ins RA, et al. T umo r R ecep to r Im aging: P roceed2 ings of the N ational Cancer Institute W o rk shop, R eview of Current W o rk, and P ro spective fo r Fu rther Investigation s [ J ]. C lin Cancer R es, 1995, 1 (8): [18 ] W ust F, Sp ies H, Johannsen B. Synthesis of M ixed2ligand O xo rhenium (V ) Comp lexes Containing M odified 3, 17Β2E stradio l[j ]. B ioo rg M ed Chem L ett, 1996, 6 (22): [ 19 ] W ust F, Scheller D, Sp ies H, et al. Synthesis of O xo rhenium (V ) Comp lexes D erived F rom 7Α2 functionalized T esto sterone: F irst R hen ium 2con2 taining T esto sterone D erivatives[j ]. Chem, 1998: Eur J Ino rg [ 20 ] Skaddan M B, W ust FR, Jonson S, et al. R adio2 chem ical Syn thesis and T issue D istribu tion of T c299m 2labeled 7Α2Sub stitu ted E stradio l Com 2 p lexes [J ]. N ucl M ed B io l, 2000, 27 (3): [ 21 ] Skaddan M B, W ust FR, Katzenellenbogen JA, et al. Synthesis and B inding A ffinities of N ovel R e2containing 7Α2substituted E stradio l Comp lex2 es: M odels fo r B reast Cancer Im aging A gents [J ]. J O rg Chem, 1999, 64 (22): [ 22 ] Kung H F, K im HJ, KungM P, et al. Im aging of Dopam ine T ranspo rter in H um ans W ith T ech2 netium 299m TRODA T 21 [J ]. 1996, 23: Eur J N ucl M ed, [ 23 ] M eegalla S, P lo ssl K, Kung M P, et al. F irst Examp le of a 99 T c m T ranspo rter Im aging A gent [ J ]. Soc, 1995, 117: Comp lex as a Dopam ine J Am Chem [ 24 ] Hoepp ing A, B rust P, Berger R, et al. N ovel R henium Comp lexes D erived F rom Α2T ropano l as Po tential L igands fo r the Dopam ine T rans2 po rter [J ]. B ioo rg M ed Chem, 1998, 6: [ 25 ],,. 99 T c m Ben2 ztrop ine ) [A ]. [J ]., 2000, 22 (1): [C ]. :, [ 26 ],,,. 99 T c m D 2 21 [A ]. [C ]. :, [ 27 ],,,. D 2 99 T c m 2M BZM [J ]., 2000, 13 (4): [ 28 ] Am artey JK, Parhar R S, A l2jamm az I, et al. Syn thesis and P relim inary Evaluation of T c2 99m 2labeled Som ato statin A nalog (RC2160) U s2 ing M ixed L igand A pp roach [J ]. M ed B io l, 2001, 28 (3): N ucl [ 29 ] F riebe M, M ahmood A, Sp ies H, et al M ixed2ligand O xo technetium (V ) Com p lexes W ith A ffinity fo r M elanom a: Synthesis and E2 valuation in V itro and in V ivo [J ]. J M ed Chem, 2000, 43 (14): [ 30 ] M astro stam atis SG, Papadopoulo s M S, P irm et2 tis IC, et al. T ridentate L igands Containing the SN S Dono r A tom Set as a N ovel Backbone fo r the D evelopm ent of T echnetium B rain2im aging A gents[j ]. J M ed Chem, 1994, 37 (20): [31 ] P irm ettis IC, Papadopoulo s M S, Ch io tellis E. N ovel 99 T c m Am inobisth io latogmono th io lato M ixed L igand Comp lexes: Structure2activ2 ity R elationsh ip s and P relim inary in V ivo V ali2 dation as B rain B lood F low Im aging A gents[j ]. J M ed Chem, 1997, 40 (16): [32 ] R ey A, Papadopoulo s M, L eon E, et al. Syn2 thesis, Characterization and B io logical Evalua2 tion of a N ovel 3+ 1 M ixed L igand 99 T c m Com 2 p lex H aving an A liphatic T h io l as Co ligand [J ]. A pp l R adiat Iso t, 2001, 54 (3): [33 ] T soukalas C, Papadopoulo s M S, M aina T, et al. Characterization and P relim inary Evaluation of E ster2m odified T echnetium 299m SN SgS M ixed L igand Comp lexes as Po tentialb rain Per2 fusion A gents [J ]. N ucl M ed B io l, 1999, 26 (3): [ 34 ],,. 99 T c m N 2( [35 ],. 99 T c m 3+ 1
10 [A ]. M ed Chem, 1999, 42 (6): [C ]. : [ 40 ],,. 99 T c m 3+ 1, [ 36 ] M iao Yubin, L iu Bo li. T echnetium 299m 2M PB2 DA, a N ew Po tential Cerebral and M yocardial Perfusion Im aging A gent: In V ivo B iodistribu2 tion in M ice [A ]. N ico linim, M azzi U. T ech2 netium, R henium and O ther M etals in Chem 2 istry and N uclear M edicine[c ]. to riali, Italy: SGE Edi2 [ 37 ] M iao Yubin, L iu Bo li. T echnetium 299m 2M PB2 DA, a N ew Po tential Cerebral Perfusion Im ag2 ing A gent: SPECT Studies in M onkey [A ]. N ico lini M, M azzi U. T echnetium, R henium and O ther M etals in Chem istry and N uclear M edicine[c ]. Italy: SGE Edito riali, [ 38 ],,,. T echnetium 299m Comp lexes in V itro and in V i2 99 T c m 2M PBDA [J ]., 2001, 21 (2): [ 39 ] N ock BA, M aina T, Yannoukako s D, et al. Glu tath ione2m ediated M etabo lism of T ech2 netium 299m SN SgS M ixed L igand Comp lexes: a P ropo sedm echanism of B rain R etention[j ]. J [J ]., 2000, 23 (11): [41 ] Kneiss T, Sp ies H, B randau W, et al. N ico ti2 nam ide2substituted Comp lexes as R edox M ark2 erṡ 1. Syn thesis and U V Investigation of R he2 n ium and T echnetium M ixed2ligand System s[j ]. J L abelled Comp R adiopharm, 1998, 41: [ 42 ] Seifert S, D rew s A, Gup ta A, et al. Stability Studies on 99m 2T echnetium Com p lexes W ith T ridentategm onodentate T h io l L igands and Pho sph ine ( Comp lexes) [J ]. R adiat Iso t, 2000, 53: A pp l [ 43 ] Syh re R, Seifert S, Sp ies H, et al. Stability V ersus R eactivity of 3 + vo [J ] M ixed2ligand Eur J N ucl M ed, 1998, 25 (7): 793 [44 ] Johannsen B, P ietzsch HJ. D evelopm ent of T e2 chnetium 299m 2based CN S R ecep to r L igands: H ave T here Been any A dvances? [J ]. M ed M o l Im aging, 2002, 29 (2): Eur J N ucl Resen t D evelopm en t of 99 Tc m Labeled Rad iopharmaceutica ls W ith 3+ 1 M ixed- ligand TAN G X iu2huan, W AN G W u2shang (N orth2w est Institu te of N uclear T echnology, X i an , Ch ina) Abstract: T he resen t developm en t of 3+ 1 m ixed2ligand labeled w ith 99 T c m disadvan tages in the research ing of w h ich are discu ssed. Key words: 99 T c m labeling; 3+ 1 m ixed2ligand; radiopharm aceu ticals is review ed, and the
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