Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine

Galactose-targeted delivery of macromolecules and drug conjugates to asialo glycoprotein receptor (ASGPR) positive cells has been widely documented in animals, although targeting in humans has never been demonstrated. In this study we report the pharmacokinetics and imaging determined in the first pa tient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)m ethacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK 2. Gradient high performance liquid chromatography (HPLC) evaluation of pla sma and urine has been combined with I-123-based imaging to show biphasic c learance of the drug from the plasma (half-lives of 78+/-1 and 990+/-15), a nd approximately 30% delivery of the drug to the hepatic region, as determi ned by planar whole body imaging at 24 h. This patient has a multifocal hep atoma, and single photon emission computed tomography (SPECT) analysis show ed a ratio of tumour tissue to normal liver uptake of approximately 1:3, at 24 h. On the basis of this patient, effective hepatic targeting can be ach ieved following an intravenous dose of 20 mg/m(2) doxorubicin as PK2, howev er the therapeutic usefulness of this targeted drug has yet to be establish ed. (C) 1999 Elsevier Science B.V. All rights reserved.