A novel method for 18 F-radiolabeling of oligodeoxynucleotides (ODNs) by a Cu-catalyzed Huisgen reaction has been developed by using the lowest possible amount of the precursor biomolecule for the realization of stoichiometry-oriented PET (positron emission tomography) chemistry. Under the optimized cyclization conditions of p- or m-azido([ 18 F]fluoromethyl)benzene and alkyne-substituted ODN (20nmol) at 40°C for 15min in the presence of CuSO 4 , TBTA [tris((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)amine], and sodium ascorbate (2:1:2), the synthesis of 18 F-labeled ODNs with sufficiently high radioactivities of 2.1–2.5GBq and specific radioactivities of 1800–2400GBq/μmol have been accomplished for use in animal and human PET studies.