PET 1

PET 1

100.000 ppm100.000 ppm 1 10 20% <12 2 10 0.00001% <12 3 10 20% <10,000 2 3 2 3

EU ICH 4 / 5

% 100 100 ppm sample HPLC/GC 90 ppm 90% 6 RSD, % 100 HPLC/GC or 100 ppm 100 ppm sample 99 ppm 101 ppm RSD 1% 7

8 HPLC GC( ) ( ) ( ) 9

[ 18 F]FDG [ 18 F]FDG GC CA02-1 7890 series GC system Agilent G3440A CA02-2 7693A series Autosampler Agilent G4514A CA02-3 7693B series Injector Agilent G4513A DB-WAX 0.52 mm i.d. 30 m, 50 μm 0-8 min; 40, 8-28 min; 40-120 28-33 min; 120, 33-53 min; 120-40 53-60 min; 40 250 0.5 μl N 2, 50 ml/min : 450 ml/min : 40 ml/min : He, 4 ml/min 10 1 GC (OQ) GC 11

STD1 3 3 95.9-100.8 STD1 3 3 0.9-2.2 STD1 3 3 3 1.8-3.4 STD1 7.04-14.1 STD1 1.0-1.2 STD1 24400-37200 STD-A2 B2 1% (R 2 ) STD1 3 0.9999 S/N STD3 1065-1388 12 1.56000 2000S/N=10 STD2 1.5 STD2 3.0 STD2 6000 STD2 6 RSD15% 13

STD1 3 3 100 10% STD1 3 3 RSD15% STD1 3 3 3 RSD15% STD1 1.5 STD1 3.0 STD1 6000 STD-A2 C2 1% S/N STD3 6 10 STD3 6 RSD15% (R 2 ) STD1 3 0.98 14 1 23 No. No. No. No. No. No. 1 Blank 13 Blank 25 STD3 1 STD2 7 STD2 13 STD3 () () 2 STD2 8 STD1 14 STD1 2 STD2 14 STD1 26 STD3 3 STD2 9 STD2 15 STD2 3 STD2 15 STD2 27 STD3 4 STD2 10 STD3 16 STD3 4 STD2 16 STD3 28 STD3 5 STD2 11 STD1 5 STD2 17 STD1 29 STD3 6 STD2 12 STD2 6 STD2 18 STD2 30 STD3 7 STD2 19 STD3 31 STD3 8 STD2 20 STD1 9 STD-A2 21 STD2 10 STD-B2 22 STD3 11 STD-C2 23 STD1 12 24 STD2 23STD1~3 15

: STD-A2 (100 ppm) STD-B2 (100 ppm) STD-C2 (100 ppm) STD-1 (1000 ppm) CH 3 OH C 2 H 5 OH CH 3 CN C 2 H 5 OH CH 3 OH CH 3 CN 0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8 16 1 No. 2 23300 27500 36400 11.6 6.90 13.9 1.2 1.1 1.1 6000 1.5 3.0 3 261493 339412 305431 4 258534 334975 300760 5 257947 332996 300139 6 252855 325042 292855 7 259714 334337 300592 8 259488 333722 301098 258338 333414 300146 2947 4682 4064 1.1 1.4 1.4 15.0 17

2 No. 2 21300 24900 35000 11.2 6.59 13.4 1.3 1.2 1.1 6000 1.5 3.0 2 263750 335827 300824 3 265409 338282 303954 4 269936 343988 308364 5 261911 332896 298461 6 266363 337703 303518 7 267460 339478 306068 265805 338029 303532 2816 3714 3550 1.1 1.1 1.2 15.0 18 3 No. 2 23700 26700 35700 11.6 6.87 13.7 1.3 1.2 1.1 6000 1.5 3.0 2 268019 349194 311693 3 259533 337499 301841 4 261209 340368 303372 5 263288 342373 304584 6 263092 343316 305025 7 261704 340842 302264 262807 342265 304797 2897 3936 3601 1.1 1.2 1.2 15.0 19

2 9 3.911 5410 10 4.650 5307 11 6.346 5106 1.0% No. 14 24400 28400 37200 11.9 7.04 14.1 1.2 1.1 1.0 6000 1.5 3.0 20 (ppm) 14 1000 1059214 15 250 250489 16 50 52077 1055.8 R 2 0.999660 0.98 (ppm) 14 1000 1228140 15 250 277520 16 50 60246 1221.2 R 2 0.998937 0.98 (ppm) 14 1000 1363543 15 250 327305 16 50 67704 1360.3 R 2 0.999815 0.98 21

(ppm) (mv) (ppm) 17 1000 1045698 991 99.07 20 1000 1054047 998 99.83 23 1000 1014611 961 96.10 1038119 20782 2.0 18 250 261570 248 99.12 21 250 262180 248 99.33 24 250 256287 243 97.10 260012 3241 1.2 19 50 52425 50 99.33 22 50 51762 49 98.05 25 50 51712 49 97.96 51966 398 0.8 100 10.0% STD1 3 15.0 (%) 22 (ppm) (mv) (ppm) 17 1000 1347833 990 99.04 20 1000 1361396 1001 100.8 23 1000 1304795 959 95.92 1338008 29552 2.2 18 250 337665 248 99.25 21 250 339247 249 99.75 24 250 330782 243 97.27 335898 4501 1.3 19 50 68567 50 100.77 22 50 67625 50 99.42 25 50 67632 50 99.43 67941 542 0.8 100 10.0% STD1 3 15.0 (%) 23

(ppm) (mv) (ppm) 17 1000 1214420 994 99.45 20 1000 1230776 1008 100.79 23 1000 1180940 967 96.71 1208712 25403 2.1 18 250 304867 250 99.86 21 250 305691 250 100.13 24 250 299149 245 97.99 303235 3563 1.2 19 50 61060 50 100.00 22 50 59981 49 98.24 25 50 60393 49 98.91 60478 544 0.9 100 10.0% STD1 3 15.0 (%) 24 STD1 STD2 STD3 1 17 19 1045698 261570 52425 120 22 1054047 262180 51762 123 25 1014611 256287 51712 2 8 10 1059570 265288 52951 2 11 13 1062539 264408 53520 2 14 16 1060198 243876 50378 3 8 10 1049515 258623 52582 3 11 13 1024106 262081 53079 3 14 16 1076108 258043 52226 1049599 259151 52293 19336 6442 932 1.8 2.5 1.8 STD1 3 15.0 25

STD1 STD2 STD3 1 17 19 1347833 337665 68567 120 22 1361396 339247 67625 123 25 1304795 330782 67632 2 8 10 1345478 337189 69128 2 11 13 1348788 335587 69789 2 14 16 1342743 303566 64764 3 8 10 1363091 336387 69122 3 11 13 1327759 340801 69853 3 14 16 1409073 335290 68596 1350106 332946 68342 28302 11368 1563 2.1 3.4 2.3 STD1 3 15.0 26 STD1 STD2 STD3 1 17 19 1214420 304867 61060 120 22 1230776 305691 59981 123 25 1180940 299149 60393 2 8 10 1183543 303345 59887 2 11 13 1184793 301911 60385 2 14 16 1165460 273368 56392 3 8 10 1189656 298122 61061 3 11 13 1155565 297006 61435 3 14 16 1265491 295650 60290 1196439 297679 60098 34439 9771 1485 2.9 3.3 2.6 STD1 3 15.0 27

26 50715 66249 58963 27 51454 67473 60289 28 50898 66586 59158 29 51935 68095 60716 30 51394 67410 59884 31 50932 66665 59413 51221 67080 59737 456 693 682 0.9 1.0 1.1 S/N 1183.0 1387.7 1064.7 S/N10 15.0 28 100 10% 99.0-105.4 RSD15% 0.2-2.7 RSD15% 1.1-7.1 1.5 6.3-12.9 3.0 1.2-1.8 6000 19234-33015 1% S/N 10 1376.9-1845.0 RSD15% 1.7-4.5 (R 2 ) 0.98 >0.9999 29

1 2 3 1.5 4.96-10.9 3.0 1.3-2.4 6000 11221-25280 RSD15% 2.9-5.2 1.5 6.92-14.0 3.0 1.0-1.3 6000 22375-37314 RSD15% 1.9-2.5 1.5 5.97-12.5 3.0 1.2-1.9 6000 17290-31313 RSD15% 0.4-0.6 30 [ 18 F]FDG 1,000 50 ppm0.98 100 10% 15% 50 ppm 1,000 50 ppm100 10% 15% 31

[ 18 F]FDG GC ppm [n=3] <50 (1 0.1) 230 1 53 1 3000 ppm 5000 ppm 410 ppm (ICH) 0 1 2 3 4 5 6 7 8 32 [ 18 F]FDG [ 18 F]FDG FDGClDGHPLC-ECD /FDGClDG ClDG 40 ppm (FASTlab) Carbopac PA-1 guard 40 mm i.d. 50 mm Carbopac PA-1 40 mm i.d. 250 mm 30 20 μl 200mM 0.3mL/min 33

/ 34 FDG 0.02 ppm/cldg 0.1 ppm FDG 0.5 ppm/cldg 2.5 ppm FDG 10 ppm/cldg 50 ppm FDG ClDG FDG ClDG FDG ClDG 0 5 10 15 20 25 30 0 5 10 15 20 25 30 0 5 10 15 20 25 30 35

STD1 3 3 92.0-113.4 STD1 3 3 0.76-8.9 STD1 3 3 3 STD1 1.4 STD1 STD1 3.2-9.3 FDG:9300 ClDG:11000 STD-A2 B2 1% (R 2 ) STD1 3 0.9999 36 FDG ClDG FDGClDG ClDG (<40 ppm) FDG,ClDG 37

FDG ClDG FDG ClDG 38 100 20% (92.0-113.4) RSD15% (0.83-8.9) RSD15% (3.2-9.3) 1.0 (1.9 2.1) 2000 (FDG:9400 ClDG:11000) STD-A2,B2 5% (R 2 ) 0.98 (>0.9999) 39

1 2 3 1.0 1.4 (R 2 ) 0.98 >0.9999 2000 9300-11000 RSD15% 0.6-1.6 1.0 1.4 (R 2 ) 0.98 >0.9999 2000 9300-11000 RSD15% 2.2-2.3 1.0 1.5 (R 2 ) 0.98 >0.9999 2000 9300-11000 RSD15% 1.6-3.5 40 [ 18 F]FDG FDG,ClDG /FDG ClDGFDG 10 0.02 ppm ClDG 50 0.1 ppm 0.98100 20% 15% FDG ClDG FDG10 0.02 ppm ClDG50 0.1 ppm100 20% 15% 41

[ 18 F]FDG HPLC-ECDFDG ClDG 2- -2- -D-FDG 2- -2--D-ClDG ppm [n=3] 0.42 0.012 11 0.43 FDG ClDG 0 5 10 15 20 25 30 42 1 2 3 43

44