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: t1/2 = 12.7 h, 76Br: t1/2 = 16.2 h, 89Zr: t1/2 = 3.3 d, 124I: t1/2 = 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 (t1/2? = 2.9 h, t1/2? = 34.9 h) and gradual reticuloendothelial clearance, with 31% of injected dose in blood retained at 24 h post-injection. © The Royal Society of Chemistry 2016.