PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments

Table 1

Summary of the most important RGD peptide tracers discussed.

Compound name	Used peptide sequence	“Labeling species”	Total prod. time	Labeling yield/spec act	Reference
𝜶𝐯𝜷𝟑/𝜶𝐯𝜷𝟓  targeting
[^18F]Galacto-RGD	c(RGDfK)	nitrophenyl-2-[^18𝐅]fluoropropionate; via amide formation	200 min	29±5% (dc^7); 40–100 GBq/µmol	[28]
	Lysine-NH2 SAA^1 modified
[^18F]Fluciclatide	- ^*1CH 2-CO-KC ^*2RGDC ^*2FC ^*1-	p-[^18𝐅]fluorobenzaldehyde; via oxime formation	75 min	40±12% (dc); 173±52 GBq/µmol	[29]
	^*1Thioether bridge; ^*2Disulfide bridge; C-terminal PEG modified; Lysine-NH2 PEGylated and aminooxy derivatized
[^18F]RGD-K5	c(RGDfK)	5-[^18F]fluoro-1-pentyne; via “click chemistry”	75 min	35% (dc); 100–200 GBq/µmol	[30]
	Lysine-NH2 SAA modified; SAA N3-functionalyzed
[^18F]FPTA-RGD2	Dimeric c(RGDyK)	[^18F]fluoro-PEG3-alkyne; via “click chemistry”	110 min	54% (dc); 100–200 GBq/µmol	[31]
	Lysine-NH2 used for dimerization; Bridged via glutamic acid; Derivatized with 5-azidopentanoic acid
[^18F]Mlt-RGD	c(RGDfPra) ^4	6 ′-deoxy-6 ′-[^18F]fluoro-β-maltosyl azide; via “click chemistry”	75 min	24% (ndc); 50–200 GBq/µmol	[32]
c(fK([^18F]SiFA-AO-N) RGD)	c(RGDfK)		p-(di-tert-butyl-[^18F]fluorosilyl)-benzaldehyde^5; via oxime formation		40 min	50–55% (ns^8); 225–680 GBq/µmol	[33]
	Lysine-NH2 aminooxy acetic acid derivatized
RGD-[^18F]ArBF3^−	c(RGDfK)	[^18F]fluoride; isotopic exchange	35 min	65% (dc); 518 GBq/µmol	[21]
	Lysine-NH2 1-succinyl-4-(2-Trifluoroboryl-1,3,5-trifluorobenzoyl)-piperazine derivatized
[^18F]Alfatide	Dimeric c(RGDyK)	[^18𝐅]aluminum fluoride species; via complexation	20 min	42% (dc); 37 GBq/µmol	[19]
	Lysine-NH2 used for dimerisation; Bridged via glutamic acid; PEG linker and NOTA for complexation
[^68Ga]NOTA-RGD	c(RGDyK)	^68Ga	10 min^2	89% (ns)	[34]
	Lysine-NH2 SCN-Bz-NOTA conjugated	via complexation		18 GBq/µmol
[^68Ga]DOTA-RGD	c(RGDfK)	^68Ga	7 min^2	>95% (ns)	[35]
	Lysine-NH2 DOTA conjugated	via complexation		—
[^68Ga]NODAGA-RGD	c(RGDfK)	^68Ga	5 min^2	>96% (ns)	[36]
	Lysine-NH2 NODAGA conjugated	via complexation		10–20 GBq/µmol
[^68Ga]TRAP(RGD)3	Trimeric c(RGDfK)	^68Ga; via complexation	5 min^2	—; 0.8–1 TBq/µmol	[20]
	Lysine-NH2 TRAP conjugated; Chelator PEG modified; Monomers linked via chelator
[^68Ga]NOPO-RGD	c(RGDfK)	^68Ga	15 min	94% (dc)	[37]
	Lysine-NH2 NOPO conjugated	via complexation		1.4 TBq/µmol
[^68Ga-(RGD-1)]^+	c(RGDyK)	^68Ga	10 min^2	97% (ns)	[38]
	Lysine-NH2 H2dedpa conjugated	via complexation		34 GBq/µmol
[^68Ga-(RGD-2)]^+	Dimeric c(RGDyK)	^68Ga; via complexation	10 min^2	99% (ns); 25 GBq/µmol	[38]
	Lysine-NH2 H2dedpa conjugated; monomers linked via chelator
𝜶𝟓𝜷𝟏  targeting
[^68Ga]α 5β 1-ANT	Nonpeptide RGD mimetic	^68Ga	—	—	[22]
	Conjugated via linker with NODAGA	via complexation
[^18F]FProp-CRRETAWAC-OH	H- * CRRETAWAC * -OH	nitrophenyl-2- [^18𝐅]fluoropropionate	200 min	—	[39]
	*Disulfide bridge	via amide formation
𝜶𝐯𝜷𝟔  targeting
[^18F]FBA-A20FMDV2	NAVPNLRGDLQVLAQKVART	solid-phase p-[^18𝐅]fluorobenzoyl labeling	130 min	3.6% (dc)	[23]
	(derived from foot-and-mouth disease virus)	via amide formation		37 GBq/µmol
[^18F]FBA-(PEG28)2-	NAVPNLRGDLQVLAQKVART	solid-phase p-[^18𝐅]fluorobenzoyl labeling	—	—	[40]
A20FMDV2	PEG linker	via amide formation
[^18F]FBA-C6-ADIBON3-PEG7- A20FMDV2	NAVPNLRGDLQVLAQKVART	[^18𝐅]FBA-C 6-ABIO	45 min	12% (dc); 70 GBq/µmol	[41]
N-terminal azido-PEG derivatized	(^18F-labelled cyclooctyne derivative); Cu-free strain-promoted “click chemistry”
[^111In]DTPA-A20FMDV2	NK(biotinyl)VPNLRGDLQVLAQKVART	^111In; via complexation	—	—	[42]
	N-terminal DTPA conjugated; 2nd amino acid replaced by biotinyl-lysine
[^64Cu]CB-TE1A1P-PEG28- A20FMDV2	NAVPNLRGDLQVLAQKVART	^64Cu; via complexation	15 min^2	>98% (ns); 22 GBq/µmol	[43]
N-terminal tetraazabicyclo[6.6.2.]hexadecane derivative conjugated
[^64Cu]DOTA-S02	RSLARTDLDHLRGR	^64Cu; via complexation	—	80% (ns); 18.5 GBq/µmol	[44]
	(sequence engrafted into loop 1 of a acyclized cystine knot scaffold); Loop 2 serine-rich; N-terminal DOTA conjugation
^18F-fluorobenzoate-R01	ILNMRTDLGTLLFR	succinimidyl-p-[^18𝐅]fluorobenzoate; via amide formation at N-terminus	45 min^2	7% (dc); —	[24]
	(sequence engrafted into loop 1 of a acyclized cystine knot scaffold); Loop 2 arginine-rich
[^99mTc]SAAC-S02	RSLARTDLDHLRGR	[^99mTc(H 2O) 3(CO) 3] ^−; Tc-tricarbonyl method	60 min^2	40% (ns); 15 GBq/µmol	[45]
	(sequence engrafted into loop 1 of a acyclized cystine knot scaffold); Loop 2 serine-rich; N-terminal SAAC^6 modified

1SAA: galactose based sugar amino acid.
²Synthesis time only (overall production time depends on several parameters, e.g., type of automated system, labeling technique, and postprocessing).
³TRAP: 1,4,7-triazacyclononane-1,4,7-tris(2-carboxyethyl)methylenephosphinic acid.
⁴Pra: propargyl glycine.
⁵Precursor is produced via isotopic exchange.
⁶SAAC: single amino acid chelate.
⁷dc: decay corrected.
⁸ns: not specified.