Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jul 21;21(7):1331-40.
doi: 10.1021/bc100137x.

Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex

William J McBride  1 , Christopher A D'Souza, Robert M Sharkey, Habibe Karacay, Edmund A Rossi, Chien-Hsing Chang, David M Goldenberg
Affiliations

Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex

William J McBride et al. Bioconjug Chem. .

Abstract

We reported previously the feasibility to radiolabel peptides with fluorine-18 ((18)F) using a rapid one-pot method that first mixes (18)F(-) with Al(3+) and then binds the (Al(18)F)(2+) complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al(18)F NOTA complexes were stable in vitro in human serum, and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100 degrees C, and the peptides could be labeled in as little as 5 min. The IMP467 peptide could be labeled up to 115 GBq/micromol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification.

PubMed Disclaimer

Figures

Figure 1
Figure 1
RP-HPLC analysis of IMP467, 18F-IMP467, and 19F-IMP467. The unlabeled peptide elutes as a single peak (A), but when radiolabeled with Al18F (18F-IMP467), two peaks are observed (B). 19F-IMP467 also showed 2 main peaks (C) [13.4 min peak is unlabeled peptide as seen in (A)]. The 14.9 min peak was isolated and evaluated over time (D-F), showing the equilibration of the isomeric counterpart (~13.0 min).
Figure 2
Figure 2
Serum stability of IMP467 as analyzed by RP-HPLC; (A) 18F-IMP467 in serum at time-zero (B) 18F-IMP467 in serum after 1 h, (C) 18F-IMP467 in serum after 4 h.
Figure 3
Figure 3
Binding of 18F-IMP467 to TF2 by SE-HPLC; (A) 18F-IMP467 after HLB purification, alone, or (B), mixed with TF2 anti-CEA x anti-HSG bsMAb.
Figure 4
Figure 4
In vivo stability of 18F-IMP467. SE- and RP-HPLC analysis of 18F-IMP467 before injection and in urine samples taken from mice 0.5 h and 1.5 h post injection. RP-HPLC shows the same elution profile in the original product and in the urine, while SE-HPLC was performed to show 18F-IMP467 eliminated in urine continued to retain binding to the TF2 anti-CEACAM5 x anti-HSG bsMAb.
Scheme 1
Scheme 1
Synthesis of bis-t-butyl NOTA
Scheme 2
Scheme 2
Synthesis of succinyl C-NETA ligand (4).
See this image and copyright information in PMC

References

    1. Miller PW, Long NJ, Vilar R, Gee AD. Synthesis of 11C, 18F, 15O, and 13N radiolabels for positron emission tomography. Angew Chem Int Ed. 2008;47:8998–9033. - PubMed
    1. Wester HJ, Schottelius M. Fluorine-18 labeling of peptides and proteins. In: Schubiger PA, Lehmann L, Friebe M, editors. PET chemistry-the driving force in molecular imaging. 2007. pp. 79–111. - PubMed
    1. Cai L, Lu S, Pike VW. Chemistry with [18F]fluoride ion. Eur J Org Chem. 2008:2853–2873.
    1. Mamat C, Ramenda T, Weust FR. Recent applications of click chemistry for the synthesis of radiotracers for molecular imaging. Mini-Rev Org Chem. 2009;6:21–34.
    1. Schirrmacher E, Wängler B, Cypryk M, Bradtmöller G, Schäfer M, Eisenhut M, Jurkschat K, Schirrmacher R. Synthesis of p-(di-tert-butyl[18F]fluorosilyl)benzaldehyde ([18F] SiFA-A) with high specific activity by isotopic exchange: a convenient labeling synthon for the 18F-labeling of N-amino-oxy derivatized peptides. Bioconjugate Chem. 2007;18:2085–2089. - PubMed

Publication types