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In vitro and in vivo evaluation of the effects of aluminum [¹⁸F]fluoride radiolabeling on an integrin αvβ₆-specific peptide.
- Source :
-
Nuclear medicine and biology [Nucl Med Biol] 2014 Jan; Vol. 41 (1), pp. 43-50. Date of Electronic Publication: 2013 Oct 08. - Publication Year :
- 2014
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Abstract
- Introduction: Incorporation of fluorine-18 ((18)F) into radiotracers by capturing ionic [(18)F]-species can greatly accelerate and simplify radiolabeling for this important positron emission tomography (PET) radioisotope. Among the different strategies, the incorporation of aluminum [(18)F]fluoride (Al[(18)F](2+)) into NOTA chelators has recently emerged as a robust approach to peptide radiolabeling. This study presents Al[(18)F](2+)-radiolabeling of an α(v)β₆ integrin-targeted peptide (NOTA-PEG₂₈-A20FMDV2) and its in vitro and in vivo evaluation.<br />Methods: Aluminum [(18)F]fluoride was prepared at r.t. from [(18)F]fluoride (40 MBq-11 GBq) and introduced into NOTA-PEG₂₈-A20FMDV2 (1) in sodium acetate (pH 4.1; 100°C, 15 min). The radiotracer Al[(18)F] NOTA-PEG₂₈-A20FMDV2 (2) was purified by HPLC, formulated in PBS and evaluated in vitro (stability; binding and internalization in α(v)β₆(+) and α(v)β₆(-) cells) and in vivo (paired α(v)β₆(+) and α(v)β₆(-) xenograft mice: PET/CT, biodistribution, tumor autoradiography and metabolites).<br />Results: The radiotracer 2 was prepared in 90 ± 6 min (incl. formulation; n=3) in 19.3 ± 5.4% decay corrected radiochemical yield (radiochemical purity: >99%; specific activity: 158 ± 36 GBq/μmol) and was stable in PBS and serum (2 h). During in vitro cell binding studies, 2 showed high, α(v)β₆-targeted binding (α(v)β₆(+): 42.4 ± 1.2% of total radioactivity, ratio (+)/(-)=8.4/1) and internalization (α(v)β₆(+): 28.3 ± 0.5% of total radioactivity, (+)/(-)=11.7/1). In vivo, 2 maintained α(v)β₆-targeted binding (biodistribution; 1 h: α(v)β₆(+): 1.74 ± 0.38% ID/g, (+)/(-)=2.72/1; 4 h: α(v)β₆(+): 1.21 ± 0.56% ID/g, (+)/(-)=4.0/1; 11% intact 2 in tumor at 1 h), with highest uptake around the tumor edge (autoradiography). Most of the radioactivity cleared rapidly in the urine within one hour, but a significant fraction remained trapped in the kidneys (4 h: 229 ± 44% ID/g).<br />Conclusion: The Al[(18)F]/NOTA-based radiolabeling was rapid and efficient, and the radiotracer 2 showed good α(v)β₆-selectivity in vitro and in vivo. However, in contrast to A20FMDV2 labeled with covalently bound [(18)F]-prosthetic groups (e.g., [(18)F]fluorobenzoic acid), 2 demonstrated significant trapping in kidneys, similar to radiometal-labeled chelator-analogs of 2.<br /> (© 2013.)
- Subjects :
- Animals
Benzoates chemistry
Cell Line, Tumor
Drug Stability
Female
Heterocyclic Compounds chemistry
Heterocyclic Compounds, 1-Ring
Mice
Peptides blood
Peptides pharmacokinetics
Positron-Emission Tomography
Substrate Specificity
Aluminum chemistry
Antigens, Neoplasm metabolism
Fluorine Radioisotopes
Integrins metabolism
Isotope Labeling methods
Peptides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9614
- Volume :
- 41
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nuclear medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 24267053
- Full Text :
- https://doi.org/10.1016/j.nucmedbio.2013.09.009