18 F-prosthetic groupSteps/reaction time1 RCY2 Reacting agent Catalytic system Overall reaction time1 (CCA) RCY2 CCA Literature
[18 F ]
fluoroalkynes 1 step, 10 min 36–81% N-(3-azidopropionyl) peptides CuI/NaAsc/DIPEA 30 min 54–99% [26 ] 4-
18 F
fluoro-1-butyne 1 step, 15 min (estimated) n.d. Glucopyranosyl azide 75–80 min 30% [27 ] 4-
18 F
Fluoro-1-butyne 1 step, 15 min
2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl azide Cu(I)/Asc/2,6-lutidine 30 min
[28 ] 5-
18 F
fluoro-1-pentyne 1 step, 15 min
1 step, 22 min
specific peptide A20FMDV2 azideCuI/Asc 66 min
[29 ] 6-
18 F
fluoro-1-hexyne 1 step, 12 min 70–85%
-(4-azido-butyl)-folic acid amideCuI 1.5 h 25–35% [30 ]
[18 F] fluoroethyl azide ([ 18 F] FEA)
1 step, 15 min 55% Terminal alkynes Excess of Cu2+ /Asc or copper powder 1 h 61–98% respectively 15–98% with copper powder [31 ] [32 ]
n.d. Caspase
Selective Isatin CuSO4 /Asc n.d.
[33 ] RGD peptides Cu2+ /Asc
[34 ] 3-Cyanoquinoline core 3 h
[35 ] Apoptosis marker ICMT11 CuSO4 /Asc/BPDS n.d. 1–3.4% n.d.c. [36 ] 5-Ethynyl-2′-deoxyuridine CuI/ascorbic acid/DIPEA
[37 ]
Tyr3
octreotate analoguesCuSO4 /Asc/BPDS 30 min (estimated) 40–64% [38 ] ICMT-11 (automated synthesis) 90 min
n.d.c.[39 ] Nucleosides CuSO4 /Asc n.d. 8–12% n.d.c. [40 ] 4-(prop-2-ynyloxy)Benzaldehyde 35 min 90% [41 ] Haloethylsulfoxides CuI/ascorbate/DIPEA n.d.
[42 ] 50% n.d.c. Nitroaromatic substrates CuSO4 /Asc 1 h [43 ]
RGDfK 60 min
[44 ] 55% Alkyne-func. 6-halopurines One-pot BPDS-copper(I) (CuSO4 /NaAsc.) 1 h 55–75% [45 ] n.d. tert-butyl ester of N-Boc-(S)-propargyl glycine
CuSO4 , NaAsc 2.5 h
[46 ] Precursor: 2 steps
18 F
FEA: 15 min. n.d. 3-Butynyl triphenyl phosphonium bromide 1 h n.d. [47 ] 1 step, 5–10 min 68–75% Alkynes of benzene rings 30 min 25–87% [48 ]
[18 F] FEA from a polyflourinated sulfonate precursor n.d. n.d. FtRGD 70–75 min 10–30% n.d.c. [49 ]
18 F-Fluoro-PEG-Alkyne 1 step, 20 min 85–94% Various azides
CuSO4 /Asc 10–30 min 71–99% [50 ] 1 step, 15 min
E(RGDyK)2 azide 110 min (estimated)
[51 ] 57% Nanoparticle azide 1 h (estimated) 58% [52 ]
[18 F]PEG3 -azide 1 step, 40 min
N-alkynylated peptide CuSO4 /Asc/BPDS 2 h (estimated)
[53 ] n.d. ZnO nanoparticle alkynes n.d. >95% [54 ]
[18 F]PEG-azide Precursor: 2 steps labeling: 1 step labeling: 58%
-(11-azido-3,6,9-trioxaundecanyl)folic acid amide CuAcetate, NaAsc 2.5 h 8.5% [55 ] 4- [18 F] fluoro-N-methyl-N-(prop-2-ynyl)- benzenesulfonamide (p [18 F] F-SA)
Precursor: 3 steps, labeling: 1 step, 80 min
Azide-functionalized neurotensin
Cu(I)-TBTA n.d. 66% [56 ] Azide-functionalized human serum albumin (HSA) 100 min 55–60% [57 ] n.d. Azide-functionalized phosphopeptide, protein (HAS), oligonucleotide (L-RNA) CuSO4 /Asc 2 h 77%/55–60%/25% [58 ] [18 F] FPy5yne
1 step, 15 min
42% N3 –(CH2 )4–CO–YKRI–OH (BG142) Tetrakis(acetonitrilo) copper(I) hexa fluorophosphates/TBTA 160 min 18.7%
[59 ] Azide-functionalized DNA CuBr/TBTA and 2,6-lutidine 276 min
2-
18 F
fluoro-3-pent-4-yn-1-yloxypyridine (
18 F
FPyKYNE) 20–25 min 20–35% Azide-functionalized RGD peptide CuSO4 /Asc 125 min 12–18% [60 ] 6-
18 F]fluoro-2-etynylpyridine 1 step, 10 min
D-amino acid analogue of WT-pHLIP azide Cu-Acetate/NaAsc 85 min 5–20% [61 ] propargyl 4- [18 F] fluorobenzoate ([18 F] PFB) Precursor: 2 steps, labeling: 1 steps, 15 min
Benzyl azide, two lysine derivatives, transglutaminase-reactive peptide
CuSO4 /Asc 1 h (estimated)
,
and
[62 ] 4-
18 F
fluoro-3-nitro-N-2-propyn-1-yl-benzamide ([18 F] FNPB) 1 step, 40 min 58% Azido-peptides cRGDfK and D4 peptide 1 h 87–93% [63 ] 1-(azidomethyl)-4- [18 F] -fluorobenzene 4 steps, 75 min 34% 4-Ethynyl-
-phenylalanine-peptide CuI/NaAsc/DIEA 90 min 90% [64 ] 4 steps, 75 min 41% siRNA alkyne CuSO4 /Asc/TBTA 120 min
[65 ] 1 step, 45 min 84% siRNA-linker (two new alkyne-bearing linkers)
CuSO4 /Asc 120 min 12% [66 ] 1-Azido-4-(3-[18 F] fluoropropoxy)benzene 4 steps, 75 min 35% 120 min
[65 ]
[18 F] (azidomethyl)fluorobenzene 1 step, 94–188 s around 40% siRNA alkyne n.d. n.d.
[67 ] 4-
18 F
Fluorophenylazide around 15% 3,4,6-tri-O-acetyl-2-deoxy-2- [18 F] fluorogluco-pyranosyl azide 1 step, 30 min
Fmoc-L-propargylglycine CuSO4 /Asc 1.5 h (estimated) 60% [68 ] 2 step, 7.5 min n.d. Alkyne-functionalized peptides (RDG, neurotensin peptoid) 75 min 17–20% n.d.c. [69 ] 52% folate alkyne Cu-Acetate/NaAsc 3 h 5–25% [70 ] 1 step, 10 min 84% RGD-peptide alkyne CuSO4 /Asc 70–75 min 16–24% [71 ] 1 step 1.3–4.7% Alkyne-bearing protein CuBr/TTMA 80–100 min 4.1% [72 ] n.d. ETA R ligand alkyne CuSO4 /Asc 70 min 20–25% n.d.c. [73 ] cyanoquinoline (EGFR) alkyne 90 min
n.d.c.[74 ] [18 F]
1 step, 20 min
n.d. Alkyne-functionalized RGD CuI /Asc
1 h n.d. [75 ] Alkyne-functionalized bombesin (BBN)
n.d.c.[76 ] 2 steps, Alkyne-functionalized RGD-boronate 30 min 15–30% [77 ] piperazine-based [18 F] AFP [18 F] BFP AFP: 4 steps, 54 h BFP: 4 steps, 72 h
18 F
AFP: 1 step, 40 min
18 F
BFP: 1 step, 40 min
18 F
AFP:
18 F
BFP:
N-Fmoc-e-azido-Lnorleucine (amino acid), SNEW peptide CuSO4 , Asc 2 h Amino acid: 59–79% SNEW peptide: 17–25% [78 ] [18 F] serine 2 steps, 125 min
cRDG-azide CuSO4 , Asc 145 min 75% [6 ]