¹⁸F-Labeling Using Click Cycloadditions

Table 2

Summary of the prosthetic groups, reaction conditions, and reaction partners applied for copper-free click fluorination.

^18F-prosthetic group	Steps/reaction time^1	RCY^2	Reacting agent	Reaction type/catalytic system	Overall reaction time^1; (CCA)	RCY^2; CCA	Literature
[^18F]COT	1 step, 15 min	71%	3,6-diaryl-s-tetrazine	inverse electron-demand DA cyclo-addition	30 min (without HPLC)	>98%	[14]
[^18F]FB-DBCO	1 step, 60 min	85%	Various azides	Strain-promoted click 1,3-dipolar cycloaddition	2 h	69–98%	[7]
TCO-derivative: Aza-DBCO-BN; (bombesin)	9 steps, —	17%	Three different [^18F]azides		30 min (without HPLC)	19–37%; (depending on azide)	[8]
[^18F]DBCO	1 step, 1 h	21%	Tyr^3-octreotide-N3(TATE)		1.5 h	95%	[9]
[^18F]TCO	[14]	[14]	Tetrazine-RGD	Inverse electron-demand DA cyclo-addition	30 min	90%	[15]
[^18F]bifunctional azadibenzocyclo-octyne	1 step, 30 min	24.5%	Alkyl azide	Strain-promoted click 1,3-dipolar cycloaddition	202±34 min	74±4.8%	[10]
[^18F]PEG4 azide	1 step, 45 min	63%	cRGD-DBCO		80 min	92%	[11]
[^18F]cyclooctyne	6–11 steps,; 30–80 h (depending on the derivative)	20–57% (depending on the derivative)	[^18F]2-fluoro-; ethylazide		30 min.	9.6–97% (depending on COT and solvent)	[12]; [79]
[^18F]trans-cyclooctene ([^18F]TCO)	1 step, 102 min	46.1±12.2%	Tetrazine modified exendin-4	Inverse electron-demand DA cycloaddition	3 h	46.7±17.3%	[16]
			Polymer modified tetrazine			89.2% in vivo	[80]
[^18F]amine-functionalised norbornene	1 step, 52 min	60±17%	Tetrazine; (peptide-/bombesin-derivatives)		82 min (without preparation of [^18F]SFB)	46–97% (depending on the tetrazine)	[18]
[^18F]FBA-C6-DBCO	[10]	[10]	𝛼V𝛽6-specific peptide	Strain-promoted click 1,3-dipolar cycloaddition	click: 40±4 min	11.9±3.2%	[13]

1Calculated as sum from all steps, for the ¹⁸F-prosthetic group, respectively, for the overall reaction leading to the click product, starting from fluorine-18.
2Radiochemical yields for the ¹⁸F-prosthetic group starting from fluorine-18 for the click reaction, respectively; decay corrected, as long as not noted elsewise.
CCA: click cycloaddition; DA: Diels Alder; DBCO: aza-dibenzocyclooctyne; TCO: trans-cyclooctyne.