Biodistribution and fate of core-labeled 125I polymeric nanocarriers prepared by Flash NanoPrecipitation (FNP)

Abstract

Non-invasive medical imaging techniques based on radionuclide imaging are powerful platforms to track the fate of radiolabeled materials for diagnostic or drug delivery applications. Polymer-based nanocarriers tagged with non-standard radionuclides with relatively long half-lives (e.g.⁶⁴Cu: t_1/2 = 12.7 h, ⁷⁶Br: t_1/2 = 16.2 h, 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 in vivo 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 in vivo. Further, PEGylated [¹²⁵I]PVPh nanocarriers exhibited relatively long circulation half-lives (t_1/2α = 2.9 h, t_1/2β = 34.9 h) and gradual reticuloendothelial clearance, with 31% of injected dose in blood retained at 24 h post-injection.