Targeting of N-(2-Hydroxypropyl)Methacrylamide Copolymer-Doxorubicin Conjugate to the Hepatocyte Galactose-Receptor in Mice: Visualisation and Quantification by Gamma Scintigraphy as a Basis for Clinical Targeting Studies

Abstract

N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing doxorubicin and galac-tosamine have been developed to target the hepatocyte galactose receptor with the aim of organ-specific chemotherapy of primary and metastatic liver disease. Previous biodistribution studies in rats and mice have used tyrosinamide incorporated into the copolymer structure to permit labelling with ¹²⁵I, enabling quantification of polymer distribution by dissection analysis. Radiolabelling of this copolymer with ¹³¹I, a radionuclide suitable for gamma scintigraphy, and the imaging analysis of its biodistribution in mice are reported. The present studies are the first to confirm the feasibility of imaging HPMA copolymer biodistribution, and such gamma scintigraphy will be of great value for clinical pharmacokinetic studies with this compound. Gamma scintigraphy is virtually the only non-invasive method of assessing hepatic uptake of this and similar materials.