This paper reports the body distribution of block copolymers (made by controlled radical polymerization) with
N-(2-hydroxypropyl)methacrylamide (
HPMA) as hydrophilic block and
lauryl methacrylate (LMA) as hydrophobic block. They form micellar aggregates in aqueous
solution. For this study the hydrophilic/hydrophobic balance was varied by incorporation of differing amounts of poly(
ethylene glycol) (PEG) side chains into the hydrophilic block, while keeping the degree of polymerization of both blocks constant. PEGylation reduced the size of the micellar aggregates (Rh=113 to 38 nm) and led to a minimum size of 7% PEG side chains.
Polymers were labeled with the positron emitter (18)F, which enables to monitor their biodistribution pattern for up to 4h with high spatial resolution. These block copolymers were investigated in Sprague-Dawley rats bearing the Walker 256 mammary
carcinoma in vivo. Organ/
tumor uptake was quantified by ex vivo biodistribution as well as small animal positron emission tomography (PET). All
polymers showed renal clearance with time. Their uptake in liver and spleen decreased with size of the aggregates. This made PEGylated
polymers--which form smaller aggregates--attractive as they show a higher blood pool concentration. Within the studied
polymers, the block copolymer of 7% PEGylation exhibited the most favorable organ distribution pattern, showing highest blood-circulation level as well as lowest hepatic and splenic uptake. Most remarkably, the in vivo results revealed a continuous increase in
tumor accumulation with PEGylation (independent of the blood pool concentration)--starting from lowest
tumor uptake for the pure block copolymer to highest enrichment with 11% PEG side chains. These findings emphasize the need for reliable (non-invasive) in vivo techniques revealing overall
polymer distribution and helping to identify
drug carrier systems for efficient
therapy.