Abstract
Hybrid imaging combining the beneficial properties of radioactivity and optical imaging within one imaging probe has gained increasing interest in radiopharmaceutical research. In this study, we modified the macrocyclic gallium-68 chelator fusarinine C (FSC) by conjugating a fluorescent moiety and tetrazine (Tz) moieties. The resulting hybrid imaging agents were used for pretargeting applications utilizing click reactions with a trans-cyclooctene (TCO) tagged targeting vector for a proof of principle both in vitro and in vivo. Starting from FSC, the fluorophores Sulfocyanine-5, Sulfocyanine-7, or IRDye800CW were conjugated, followed by introduction of one or two Tz motifs, resulting in mono and dimeric Tz conjugates. Evaluation included fluorescence microscopy, binding studies, logD, protein binding, in vivo biodistribution, µPET (micro-positron emission tomography), and optical imaging (OI) studies. 68Ga-labeled conjugates showed suitable hydrophilicity, high stability, and specific targeting properties towards Rituximab-TCO pre-treated CD20 expressing Raji cells. Biodistribution studies showed fast clearance and low accumulation in non-targeted organs for both SulfoCy5- and IRDye800CW-conjugates. In an alendronate-TCO based bone targeting model the dimeric IRDye800CW-conjugate resulted in specific targeting using PET and OI, superior to the monomer. This proof of concept study showed that the preparation of FSC-Tz hybrid imaging agents for pretargeting applications is feasible, making such compounds suitable for hybrid imaging applications.
Highlights
Various imaging modalities have evolved as valuable tools for molecular imaging of human diseases
The fusarinine C (FSC)-based Tz-bearing hybrid imaging agents were accessible by a straightforward
The FSC-based Tz-bearing hybrid imaging agents were accessible by a straightforward three
Summary
Various imaging modalities have evolved as valuable tools for molecular imaging of human diseases. When used as a stand-alone technique, every method shows benefits and limitations [1] so combining different modalities, namely dual-modality- (DMI) or hybrid imaging (HI), is a field with increasing attraction. Optical imaging (OI), for example, is characterized by excellent sensitivity to acquire morphological information but poor tissue penetration limits its applicability for non-invasive. Single photon emission- (SPECT) and positron emission tomography (PET) show excellent tissue penetration and allow to obtain functional information with high sensitivity. Due to the lack of morphological information unsurprisingly computed tomography (CT) or magnetic resonance (MR) are used to add morphological details.
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