1 research outputs found
<sup>18</sup>F‑Labeled-Bioorthogonal Liposomes for <i>In Vivo</i> Targeting
Liposomes
are attractive vehicles for the controlled release of
drugs and cytotoxins and have a long-standing history in medical research
and clinical practice. In addition to established therapeutic indications,
liposomes have several favorable properties for molecular imaging,
including high stability and the ability to be labeled with radioisotopes,
as well as paramagnetic and fluorescent contrast agents. However,
long circulation times and difficulties in creating targeted liposomes
have proven challenges for imaging. In this study, we have addressed
these limitations using a recently developed strategy for bioorthogonal
conjugation, the reaction between tetrazines and <i>trans</i>-cyclooctenes. By coating radiolabeled liposomes with <i>trans</i>-cyclooctene and pretargeting with a tetrazine coupled to a targeted
peptide, we were able to selectively enhance the retention of liposomes
and bind them to tumor tissue in live animals. The rapid reaction
between tetrazines and <i>trans</i>-cyclooctenes allowed
imaging to be performed with the short-lived PET tracer <sup>18</sup>F, yielding signal-to-background activity ratios of 7:1. The covalent,
bioorthogonally driven tumor-targeting of liposomes by <i>in
vivo</i> click chemistry is promising and should be explored
for more selective and rapid delivery of radiodiagnostics and radiotherapeutics,
two classes of drugs which particularly benefit from fast clearance,
low nonspecific binding, and the associated reduced toxicity to kidneys
and bone marrow