GAMMA-SCINTIGRAPHY OF THE BIODISTRIBUTION OF I-123 LABELED N-(2-HYDROXYPROPYL)METHACRYLAMIDE COPOLYMER-DOXORUBICIN CONJUGATES IN MICE WITH TRANSPLANTED MELANOMA AND MAMMARY-CARCINOMA

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin conj ugate is currently under clinical evaluation as a new antitumour agent . It has been shown previously that such conjugates exhibit selective tumour accumulation. In this study HPMA copolymer doxorubicin conjugat es of low (LMW) or high (HMW) molecular weight were synthesised (which had a weight average molecular weight (Mw) of 25,000 and 94,000 respe ctively) and additionally contained a small amount (1 mol%) of the com onomer methacryloyltyrosinamide to permit labelling with [I-123 or I-1 25]iodide. Gamma camera imaging using the I-123-labelled probes was us ed to follow time-dependent biodistribution after intraperitoneal (i.p .) or intravenous (i.v.) administration to mice bearing subcutaneously either B16F10 melanoma or a mammary carcinoma. Imaging showed more ra pid clearance of LMW conjugate from the peritoneal cavity than HMW con jugate. The images of mice given the LMW conjugate revealed rapid urin ary excretion of radioactivity after both i.p. and i.v. injection with an early high concentration of tracer in the bladder, and subsequentl y a very high concentration in the kidneys, which came to dominate the views. Dissection analysis 2 days after administration of the LMW con jugate revealed a kidney level of radioactivity corresponding to 25-40 %dose/g tissue in mice bearing the two tumour models. Following admin istration of the HMW conjugate kidney accumulation at 2 days was less due to retention of the higher molecular weight polymer molecules in t he circulation, and spleen and liver displayed the highest concentrati ons of radioactivity. The tumour accumulation of LMW and HMW conjugate s was; mammary carcinoma 3.18 and 5.29 % dose/g respectively; B16F10 m elanoma 3.23 and 8.82 %dose/g although these levels of tracer enabled visualisation in the images of the mammary carcinoma with HMW conjugat e at later time points. The smaller size of the B16F10 tumour masses d id not permit clear visualisation.