This distribution behavior was not expected. One major difference between compound III and compounds I and II is that the labeled moiety was at the periphery of the PEO chains in III, as opposed to the well protected core in compounds I and II. This could possibly account for the liver uptake since it was previously observed that iodophenol containing PEGs would expose the methoxy iodophenol to the putative liver receptors whereas the iodophenol would be sterically hindered in compounds I and II (37). Another possibility is that the iodine-containing moiety was hydrolyzed from the polymer and incorporated into the liver rather than the model compound itself. Given the rapidity of uptake in the liver, this is unlikely. Moreover, iodinated polymer recovered from serum eluted in the high molecular weight fraction on a G-50 spin column. Thus, we attributed the biodistribution profile of compound III to the exposed iodinated phenol. Despite the uptake of III into the liver, we decided to prepare a polymer−doxorubicin conjugate with compound III for further biodistribution studies.