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Eur J Nucl Med Mol Imaging. 2011 Sep;38(9):1732-41. doi: 10.1007/s00259-011-1847-4. Epub 2011 May 27.

One-step radiosynthesis of ¹⁸F-AlF-NOTA-RGD₂ for tumor angiogenesis PET imaging.

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  • 1Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford University, 1201 Welch Road, Lucas Expansion, P095, Stanford, CA 94305-5344, USA.



One of the major obstacles of the clinical translation of (18)F-labeled arginine-glycine-aspartic acid (RGD) peptides has been the laborious multistep radiosynthesis. In order to facilitate the application of RGD-based positron emission tomography (PET) probes in the clinical setting we investigated in this study the feasibility of using the chelation reaction between Al(18)F and a macrocyclic chelator-conjugated dimeric RGD peptide as a simple one-step (18)F labeling strategy for development of a PET probe for tumor angiogenesis imaging.


Dimeric cyclic peptide E[c(RGDyK)](2) (RGD(2)) was first conjugated with a macrocyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and the resulting bioconjugate NOTA-RGD(2) was then radiofluorinated via Al(18)F intermediate to synthesize (18)F-AlF-NOTA-RGD(2). Integrin binding affinities of the peptides were assessed by a U87MG cell-based receptor binding assay using (125)I-echistatin as the radioligand. The tumor targeting efficacy and in vivo profile of (18)F-AlF-NOTA-RGD(2) were further evaluated in a subcutaneous U87MG glioblastoma xenograft model by microPET and biodistribution.


NOTA-RGD(2) was successfully (18)F-fluorinated with good yield within 40 min using the Al(18)F intermediate. The IC(50) of (19)F-AlF-NOTA-RGD(2) was determined to be 46 ± 4.4 nM. Quantitative microPET studies demonstrated that (18)F-AlF-NOTA-RGD(2) showed high tumor uptake, fast clearance from the body, and good tumor to normal organ ratios.


NOTA-RGD(2) bioconjugate has been successfully prepared and labeled with Al(18)F in one single step of radiosynthesis. The favorable in vivo performance and the short radiosynthetic route of (18)F-AlF-NOTA-RGD(2) warrant further optimization of the probe and the radiofluorination strategy to accelerate the clinical translation of (18)F-labeled RGD peptides.

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