Biodistribution and fate of core-labeled¹²⁵I polymeric nanocarriers prepared by Flash NanoPrecipitation (FNP)

Abstract

Non-invasive medical imaging techniques such as positron emission tomography (PET) imaging are powerful platforms to track the fate of radiolabeled materials for diagnostic or drug delivery applications. Polymer-based nanocarriers tagged with non-standard PET radionuclides with relatively long half-lives (e.g. ⁶⁴Cu: t_1/2 = 12.7 h, ⁷⁶Br: t_1/2 = 16.2h, ⁸⁹Zr: t_1/2 = 3.3 d, ¹²⁴I: t_1/2 = 4.2 d) may greatly expand applications of nanomedicines in molecular imaging and therapy. However, radiolabeling strategies that ensure stable <i>in vivo</i> association of the radiolabel with the nanocarrier remain a significant challenge. In this study, we covalently attach radioiodine to the core of pre-fabricated nanocarriers. First, we encapsulated polyvinyl phenol within a poly(ethylene glycol) coating using Flash NanoPrecipitation (FNP) to produce stable 75 nm and 120 nm nanocarriers. Following FNP, we radiolabeled the encapsulated polyvinyl phenol with ¹²⁵I via electrophilic aromatic substitution in high radiochemical yields (> 90%). Biodistribution studies reveal low radioactivity in the thyroid, indicating minimal leaching of the radiolabel <i>in vivo</i>. Further, PEGylated [¹²⁵I]PVPh nanocarriers exhibited relatively long circulation half-lives (t_{1/2 α} = 2.9 h, t_{1/2 β} = 34.9 h) and gradual reticuloendothelial clearance, with 31% of injected dose in blood retained at 24 h post-injection.