Rapid ¹⁸F-Labeling and Loading of PEGylated Gold Nanoparticles for in Vivo Applications

Abstract

Water-soluble 3 nm maleimide-terminated PEGylated gold nanoparticles (maleimide-AuNP) were synthesized in both partially hydrolyzed and nonhydrolyzed forms. Both of these maleimide-AuNPs, when reacted with the silicon-fluorine prosthetic group [(18)F]SiFA-SH, resulted in radiolabeled AuNPs. These NPs were readily purified with high radiochemical yields (RCY) of 60-80% via size exclusion chromatography. Preliminary small animal positron emission tomography (PET) measurements in healthy rats gives information about the pathway of excretion and the stability of the radioactive label in vivo. The partially hydrolyzed [(18)F]SiFA-maleimide-AuNPs shows uptake in the brain region of interest (ROI) (> 0.13%ID/g) which was confirmed by ex vivo examination of the thoroughly perfused rat brain. The multiple maleimide end groups on the AuNP surface also allows for the simultaneous incorporation of [(18)F]SiFA-SH and a bioactive peptide (cysteine-modified octreotate, cys-TATE, which can bind to somatostatin receptor subtypes 2 and 5) in a proof-of-concept study. The well-defined Michael addition reaction between various thiol containing molecules and the multifunctionalized maleimide-AuNPs thus offers an opportunity to develop a new bioconjugation platform for new diagnostics as well as therapeutics.

Radiolabeled inorganic nanoparticles for positron emission tomography imaging of cancer: an overview

“…In a similar study, Zhu et al reported the synthesis of water-soluble maleimide-terminated PEGylated Au nanoparticles (3 nm diameter) which could be radiolabeled by reaction with silicon-fluorine prosthetic group, [ 18 F]SiFA -SH and used for PET imaging in healthy rats. 51 In another study, Wang et al reported the synthesis of Au nanocages of two different sizes (55 nm and 30 nm in edge length) and used them for radiolabeling with 64 Cu. 52 In vivo PET imaging studies in normal C57BL/6 mice showed that the 30 nm nanocages had a greatly improved biodistribution profile than 55 nm nanocages, together with higher blood retention and lower uptake in liver and spleen.…”

18F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

“…[30] The lipophilic feature of silicon functionalities may increase non-specific binding; therefore, structural modifications including PEGylation and/or zwitterion formation have been developed to reduce the lipophilicity of 18 F-Si labeled compounds. [31] Recently, Niedermoser, Schirrmacher and Wangler et al have developed a new precursor for isotope exchange to achieve 18 F-labeling of somatostatin receptor analogs (Figure 6E). [32] In this work, the newly developed SiFAlin-derivatized somatostatin analog 37 was synthesized and radiolabeled with 53% RCY (non-decay corrected) and 44–63 GBq/μmol (1.3–1.7 Ci/μmol) molar activity from SiFAlin 36 .…”

Radio-nanomaterials for biomedical applications: state of the art

“…For example, water-soluble, maleimideterminated PEGylated gold nanoparticles (AuNPs) were radiolabeled by the [ 18 F]-silicon-fluorine prosthetic group and attached by a cysteine-modified octreotate (binds to somatostatin receptor [SSTR] subtypes 2 and 5) for delineation of brain tumors (46). Aptamer- and antibody (C225)-coated HAuNS (both targeted to epidermal growth factor receptors [EGFR]) were evaluated in another report for targeting of human OSC-19 oral tumors (EGFR + ) post labeling with 111 In (47).…”