Stable Radiolabeling of Sulfur-Functionalized Silica Nanoparticles with Copper-64

Abstract

Nanoparticles labeled with radiometals enable whole-body nuclear imaging and therapy. Though chelating agents are commonly used to radiolabel biomolecules, nanoparticles offer the advantage of attaching a radiometal directly to the nanoparticle itself without the need of such agents. We previously demonstrated that direct radiolabeling of silica nanoparticles with hard, oxophilic ions, such as the positron emitters zirconium-89 and gallium-68, is remarkably efficient. However, softer radiometals, such as the widely employed copper-64, do not stably bind to the silica matrix and quickly dissociate under physiological conditions. Here, we overcome this limitation through the use of silica nanoparticles functionalized with a soft electron-donating thiol group to allow stable attachment of copper-64. This approach significantly improves the stability of copper-64 labeled thiol-functionalized silica nanoparticles relative to native silica nanoparticles, thereby enabling in vivo PET imaging, and may be translated to other softer radiometals with affinity for sulfur. The presented approach expands the application of silica nanoparticles as a platform for facile radiolabeling with both hard and soft radiometal ions.

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

“…74 The radiolabeling and in vivo stability of the nanoplatform were found to be dependent on the concentration and location of deprotonated silanol groups in the nanoparticles. In similar studies, Shaffer et al developed chelator-free methods for radiolabeling 68 Ga 26 and 64 Cu 75 with mesoporous silica nanoparticles. These radiolabeling studies might be useful in understanding the short and long term fate of mesoporous silica nanoparticles when administered in vivo for PET image guided drug delivery applications.…”

Cancer imaging using surface-enhanced resonance Raman scattering nanoparticles

“…For instance, the gold nanoparticle core serves as a contrast agent for CT and optoacoustic imaging, and the silica shell can be coated with gadolinium for contrast on magnetic resonance imaging (MRI) 6 . Additionally, the high affinity of silica for radioisotopes such as 89 Zr and 68 Ga can enable whole-body imaging capabilities using positron-emission tomography (PET) 9,26 . Apart from detection of premalignant and malignant lesions, nanoparticles have been shown to accumulate in atherosclerotic plaques and in ischemic lesions following myocardial infarction and therefore can play an important role in cardiovascular disease (CVD) imaging as well 27,28 .…”

Intrinsic and Stable Conjugation of Thiolated Mesoporous Silica Nanoparticles with Radioarsenic

“…41 Previously, MSN has been radiolabeled with 64 Cu through surface-functionalized chelator-based methods 11,42 and through a chelator-free incorporation of 89 Zr and other radiometals in the silica framework. 18,43,44 Additionally, thiol-modified MSN has recently been shown to radiolabel with radioarsenic. 21 The present work aims to build upon this latter work and further characterize the arsenic–silica bioconjugation and in vitro and in vivo of thiolated-mesoporous-silica-bound radioarsenic.…”