Abstract
A rapid one-step 18F labeling reaction with fluoridealuminum complex, which is based on chelation chemistry, has received a surge of interest for 18F radiolabeling of peptides. In this study, a non-peptidic bivalent integrin αvβ3 antagonist (bivalent-IA) was conjugated with 1,4,7-triazacyclononane-1,4-diiacetic acid (NODA). A novel 18F labeled radiotracer, 18F-bivalent-IA, was developed via one step 18F-AlF/NODA chelation reaction in aqueous phase with high radiochemical yield (65-75%, decay corrected) and good specific activity (750-850 mCi/μmol). The tumor integrin targeting efficiency and in vivo pharmacokinetic profile of 18F-bivalent-IA were evaluated in U-87 MG (integrin positive) and MDA-MB-231 (integrin negative) models by small-animal PET/CT scan followed by a biodistribution study. The PET/CT and ROI results showed high tumor uptake of 18F-bivalent-IA in U-87 MG tumor-bearing mice from 5 to 120 min p.i. with good contrast, and the U-87 MG tumor uptake values (6.35 ± 0.67%ID/g, at 1 h p.i.) were 6 times higher than those of MDA-MB-231 tumor (1.05 ± 0.12%ID/g, at 1 h p.i.) (P < 0.0001) which correlated with the integrin αvβ3 expression in tumor tissues confirmed by immunohistochemistry. Co-injection of the 18F-bivalent-IA with 6 nmol (6 μg) of nonradioactive bivalent-IA effectively blocked tumor uptake demonstrating the integrin αvβ3-specificity. In conclusion, the first 18F labeled non-peptidic bivalent integrin αvβ3 targeting radiotracer, 18F-bivalent-IA, was developed and proved to be a highly potent and specific PET radiopharmaceutical for noninvasive imaging of integrin αvβ3, which plays a critical role in tumor angiogenesis and metastasis.
Original language | English (US) |
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Pages (from-to) | 24-28 |
Number of pages | 5 |
Journal | Bioconjugate chemistry |
Volume | 26 |
Issue number | 1 |
DOIs | |
State | Published - Jan 21 2015 |
ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Biomedical Engineering
- Pharmacology
- Pharmaceutical Science
- Organic Chemistry