18F-labeled galacto and PEGylated RGD dimers for PET imaging of αvβ3 integrin expression.
OBJECTIVE
In vivo imaging of α(v)β(3) has important diagnostic and therapeutic applications. (18)F-Galacto-arginine-glycine-aspartic acid (RGD) has been developed for positron emission tomography (PET) imaging of integrin α(v)β(3) expression and is now being tested on humans. Dimerization and multimerization of cyclic RGD peptides have been reported to improve the integrin α(v)β(3)-binding affinity due to the polyvalency effect. Here, we compared a number of new dimeric RGD peptide tracers with the clinically used (18)F-galacto-RGD.


METHODS
RGD monomers and dimers were coupled with galacto or PEG(3) linkers, and labeled with (18)F using 4-nitrophenyl 2-(18)F-fluoropropionate ((18)F-NFP) or N-succinimidyl 4-(18)F-fluorobenzoate as a prosthetic group. The newly developed tracers were evaluated by cell-based receptor-binding assay, biodistribution, and small-animal PET studies in a subcutaneous U87MG glioblastoma xenograft model.


RESULTS
Starting with (18)F-F(-), the total reaction time for (18)F-FP-SRGD2 and (18)F-FP-PRGD2 is about 120 min. The decay-corrected radiochemical yields for (18)F-FP-SRGD2 and (18)F-FP-PRGD2 are 52 ± 9% and 80 ± 7% calculated from (18)F-NFP. Noninvasive small-animal PET and direct tissue sampling experiments demonstrated that the dimeric RGD peptides had significantly higher tumor uptake as compared to (18)F-galacto-RGD.


CONCLUSIONS
Dimeric RGD peptide tracers with relatively high tumor integrin-specific accumulation and favorable in vivo kinetics may have the potential to be translated into clinic for integrin α(v)β(3) imaging.
Liu
Shuanglong
S
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd., P095, Stanford, CA 94305-5484, USA.
Liu
Zhaofei
Z
Chen
Kai
K
Yan
Yongjun
Y
Watzlowik
Petra
P
Wester
Hans-Jürgen
HJ
Chin
Frederick T
FT
Chen
Xiaoyuan
X
D000818:Animals; D045744:Cell Line, Tumor; D019281:Dimerization; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005690:Galactose / Q000737:chemistry*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D005690:Galactose