M.-R. Zhang et al. / Journal of Fluorine Chemistry 125 (2004) 1879–1886
1885
100 mL/min) at 130 8C for 2 min and cooled into another
vessel containing solvents (500 mL) for trapping at À15 to
À20 8C. The radiochemical yield of [18F]FCH2I was 14–
31% (n = 13) based on the total [18F]FÀ recovered from the
target room. The radiochemical purity of [18F]FCH2I was
assayed by analytical HPLC (FinePak Sil C18-T5, Ø 4.6 mm
 250 mm). The mobile phase was KH2PO4 (10 mM)/
CH3CN (1/1) with a flow rate of 2 mL/min and the retention
time was 4.3 min for [18F]FCH2I. Confirmation for the
identity of [18F]FCH2I was achieved by co-injection with
the authentic non-radioactive FCH2I prepared by the reac-
tion of CH2I2 with HgF2 [2].
rate (6 mL/min). The fraction corresponding to the desired
radioactive product was collected in a rotary evaporator and
evaporated to dryness at about 40 8C under reduced pres-
sure. After the residue was re-dissolved in 3 mL of saline,
the product was obtained with a radiochemical purity of
>95%. Confirmation for the identity of each product was
achieved by co-injection with the non-radioactive authentic
sample using the analytical HPLC column.
The stability of the [18F]fluoromethylated compound in
its prepared form was evaluated by monitoring its radio-
chemical purity using the HPLC system described above.
After these products were maintained for 180 min, their
radiochemical purities were measured.
4.10. Determination on stability of [18F]FCH2I in
various solvents
The stability of [18F]FCH2I in various trapped solvents
was evaluated by monitoring its radiochemical purity using
the HPLC system described above. After leaving the solu-
tion for the designated time spans, the radiochemical purities
of the [18F]FCH2I solutions were measured according to the
analytical condition described above, respectively.
Acknowledgements
The authors thank the staff of Cyclotron Operation Sec-
tion and Radiopharmaceutical Chemistry Section of
National Institute of Radiological Sciences (NIRS) for their
support in the operation of the cyclotron and production of
the radioisotopes.
4.11. Reactions of [18F]FCH2I with phenol, thiophenol,
amide and amine
References
[18F]FCH2I (80–370 MBq) was trapped into a solution of
anhydrous DMF (500 mL) containing each substrate (0.8–
1.1 mg) and base (if required, NaH: 10 mL, 1.5 g/20 mL
DMF) at À15 to À20 8C. Then the reaction mixture was
warmed to 25 8C and kept for 10 min. After the reaction was
terminated by adding CH3CN/H2O (1/1, 200 mL), the radio-
chemical yields of [18F]fluoromethylated products were
determined by analytic HPLC.
[1] C. Wakselman, Reactions of organic fluorine compounds: alkylation.,
in: M. Hudlicky, A.E. Pavlath (Eds.), Chemistry of Organic Fluorine
Compounds II ACS Monograph., 187 (1995) 446–496.
[2] D. Burton, P. Greenlimb, J. Org. Chem. 40 (1975) 2796–2799.
[3] Q.-L. Zheng, M.S. Berridge, Appl. Radiat. Isot. 52 (2000) 55–61.
[4] (a) H. Bohme, M. Hakke, Chem. Ber. 100 (1967) 3609–3615;
(b) H. Bohme, M. Hilp, Chem. Ber. 103 (1970) 104–108.
[5] (a) U. Schollkopf, A. Lerch, J. Paust, J. Chem. Ber. 96 (1963) 2266–
2275;
The analytical conditions for the fluoromethylated pro-
ducts [18F]1a–4a and [18F]13a,14a were as follows. [18F]1a:
J’sphore ODS H80 (Ø 4 mm  150 mm), CH3CN/H2O (1/
1), 2 mL/min, 5.6 min. [18F]2a: J’sphore ODS H80 (Ø 4 mm
 150 mm), CH3CN/H2O (6.5/3.5), 2 mL/min, 4.9 min.
[18F]3a: Capcell Pak C18 (Ø 4.6 mm  250 mm),
CH3OH/H2O/Et3N (7/3/0.05), 1.7 mL/min, 7.3 min.
[18F]4a: J’sphore ODS H80 (Ø 4 mm  150 mm),
CH3CN/H2O (7/3), 2 mL/min, 7.2 min. [18F]13a and
[18F]14a: FinePak Sil C18-T5 (Ø 4.6 mm  150 mm),
KH2PO4 (10 mM)/CH3CN (4/1), 2.0 mL/min, 5.1 and
3.2 min.
(b) U. Schollkopf, H. Gorth, Liebigs Ann. Chem. 709 (1967) 97–103.
[6] H.H. Coenen, M. Colosimo, M. Schuller, G. Stocklin, J. Label. Comp.
Radiopharm. 23 (1986) 587–595.
[7] J. Berman, O. Eskola, P. Lehikoinen, O. Solin, Appl. Radiat. Isot. 54
(2001) 927–933.
[8] T.R. Degrado, R.E. Coleman, S. Wang, S.W. Baldwin, M.D. Orr, C.N.
Robertson, T.J. Polascik, D.T. Price, Cancer Res. 61 (2000) 110–117.
[9] K. Hara, J. Nucl. Med. 42 (2001) 1815–1817.
[10] R. Iwata, C. Pascali, A. Bogni, S. Furomoto, K. Terasaki, K. Yanai,
Appl. Radiat. Isot. 57 (2002) 347–352.
[11] R. Iwata, S. Furumoto, C. Pascali, A. Bogni, K. Ishiwata, J. Label.
Comp. Radiopharm. 26 (2003) 555–566.
[12] J. Zessin, O. Eskola, P. Brust, J. Bergman, J. Steinbach, P. Lehikoinen,
O. Solin, B. Johannsen, Nucl. Med. Biol. 28 (2001) 857–863.
[13] M.-R. Zhang, J. Maeda, K. Furutsuka, Y. Yoshida, M. Ogawa, T.
Suhara, K. Suzuki, Biorg. Med. Chem. Lett. 13 (2003) 201–204.
[14] O. Matsson, J. Persson, S. Axelsson, B. Langstrom, J. Am. Chem. Soc.
115 (1993) 5288–5289;
4.12. Determination for stability of [18F]fluoromethylated
compounds
After the reaction was finished, the [18F]fluoromethylated
compound was purified from the radioactive mixture using a
reverse-phase HPLC system. The HPLC conditions for
purifying the corresponding products were similar to the
analytical conditions listed above, with the exception of
semi-preparative column (Ø 10 mm  250 mm) and flow
(b) J. Persson, S. Axelsson, O. Matsson, J. Am. Chem. Soc. 118
(1996) 20–23;
(c) P. Ryberg, O. Matsson, J. Am. Chem. Soc. 123 (2001) 2712–2718.
[15] M.-R. Zhang, A. Tsuchiyama, T. Haradahira, Y. Yoshida, K. Furut-
suka, K. Suzuki, Appl. Radiat. Isot. 52 (2002) 335–342.
[16] A.E. Van Arkel, E. Janetzky, Recl. Trav. Chim. Pays-Bas 56 (1937)
167–169.