Optimized and accessible immuno-PET using lipid nanoparticle-mediated in vivo bioreactor

Immune-mediated positron emission tomography (immunoPET) is an emerging imaging technique that enables non-invasive in vivo pathology assessment, analogous to what is commonly used in immunohistology. This is enabled by imaging of radiolabeled antibodies or antibody fragments. However, current immunoPET approaches, including pre-targeted strategies, suffer from relatively poor signal-to-background ratio, in part because of the suboptimal pharmacokinetics of the imaging probes used. Moreover, widespread clinical translation of current immunoPET technologies is hampered by the complexity of manufacturing individual probes, supply chain constraints, and the complex workflow requiring patients to present to the hospital multiple times in strict coordination for any individual immunoPET study. In this Trailblazer proposal, we posit that lipid nanoparticle (LNP) technology can be harnessed for immunoPET to address several of the outlined concerns. Extensive advances in LNP-mRNA now enable patients to be transient in vivo bioreactors for therapeutic protein production, including antibodies and antibody fragments, offering an opportunity to improve the kinetics of a protein-based imaging agent. Furthermore, LNP can be delivered via several routes that potentially enable administration at a local pharmacy or even by self-administration. The purpose of this Trailblazer proposal is to establish LNP-immunoPET as a viable platform for clinical molecular imaging. We will assess the ability of LNP-mRNA to synthesize imageable antibody-based probes through radiohapten interactions. Furthermore, we will assess the relationship of LNP administration route on the viability of the LNP-immunoPET approach. If successful, LNP-immunoPET will offer a revolutionary strategy that will advance the capability of immunoPET and extend the reach of molecular imaging and therapeutics for our patient population.