Synthetic macromolecules such as copolymers of
N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(
HPMA) was prepared for labelling by introducing
biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of
biotin-pHPMA was visualised using a
streptavidin-
alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated
polymer could be easily detected in tissues fixed in 10%
paraformaldehyde-
phosphate buffer at 4 degrees C for 48 h. While
biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate
carcinoma (Dunning R3327-AT1). How
biotin as a label influences the biodistribution of poly(
HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(
HPMA) with
biotin-pHPMA. The organ distribution patterns of the two
polymers correlated well, except with respect to kidney. It is assumed that the accumulation of
biotin-pHPMA in the distal tubuli is due to a
biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules.