Abstract
Integrins have become increasingly attractive targets for molecular imaging of angiogenesis with positron emission tomography or single-photon emission computed tomography, but the reliable production of radiopharmaceuticals remains challenging. A strategy for chemoselective labeling of the integrin ligand - c(RGDyK) peptide - has been developed on the basis of the Cu(I)-catalyzed conjugation reaction. Recently, we reported a nucleophilic detagging and fluorous solid-phase extraction method providing an easy way to implement an approach for obtaining 2-[18F]fluoroethyl azide. In this work, we report the practical use of this method for the preparation of the 2-[ 18F]fluoroethyl-triazolyl conjugated c(RGDyK) peptide: [ 18F]FtRGD. The two-step, two-pot synthesis, HPLC purification, and reformulation could be readily performed with a standard nucleophilic radiofluorination synthesizer (GE TRACERlab FXFN), with minimal modifications. [18F]FtRGD was obtained in a solution for injection (>500 MBq/mL) in 10-30% nondecay-corrected radiochemical yield, excellent radiochemical purity (>98%), and 28 ± 13 GBq/μmol specific activity. [18F]FtRGD (Ki = 54 ± 14 nM for αVβ3 and 1.7 ± 0.2 nM for αVβ5) was evaluated in mice and showed good stability in vivo, good tumor-to-background ratio (1.6 ± 0.3 %ID/g at 1.5 h post-injection in U87-MG tumors), and rapid urinary excretion. Therefore, [18F]FtRGD proved valuable for preclinical positron emission tomography imaging of integrin expression. A two-step, two-pot, and chemoselective strategy was developed for the radiolabeling of the c(RGDyK) peptide. Via nucleophilic detagging and fluorous solid-phase extraction, we obtain 2-[18F]fluoroethyl azide that is further used in the CuAAC conjugation reaction to prepare the 2-[18F]fluoroethyl-triazolyl conjugated c(RGDyK) peptide: [18F]FtRGD. [18F]FtRGD displayed a good affinity and selectivity for integrins both in vitro and in vivo, and proved valuable for preclinical positron emission tomography imaging of integrin expression.
Original language | English |
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Pages (from-to) | 42-49 |
Number of pages | 8 |
Journal | Journal of Labelled Compounds and Radiopharmaceuticals |
Volume | 56 |
Issue number | 2 |
DOIs | |
Publication status | Published or Issued - Feb 2013 |
Externally published | Yes |
Keywords
- CuAAC
- F-18
- PET
- RGD
- angiogenesis
- fluorous
- integrins
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Radiology Nuclear Medicine and imaging
- Drug Discovery
- Spectroscopy
- Organic Chemistry