Question: 

Tumors show in contrast to normal tissues a higher vascular permeability allowing macromolecules to leave circulation and to accumulate in the tumor tissue. This EPR effect makes these structures suitable as transporters for chemotherapeutic drugs. However the eligibility of these polymers depends on the distribution kinetics within the organism.

Methods: 

Two different polymer structures (hydrophilic HPMA homopolymers and amphiphilic HPMA-ran-LMA copolymers) were synthesized each of them with two different molecular weights (10 kDa and 40–50 kDa). These macromolecules were labeled with ¹⁸F in order to analyze body distribution by ex vivo measurements concerning the polymer accumulation in various organs (biodistribution) and by non-invasive mPET imaging.

Results: 

The molecular weight was the most prominent parameter responsible for renal excretion for both homo- and copolymers. Small polymers showed much higher concentrations in the kidney as compared to large ones. The liver uptake was most pronouncedly affected by the molecular structure. The liver concentration of large homopolymers was 3-times higher than for all other polymer systems. The results of spleen accumulation were comparable to those of the liver. Finally, the blood concentrations of both copolymers were much higher than the homopolymers which was confirmed by mPET images.

Conclusions: 

These results clearly show marked differences in biodistribution depending on the structure and the molecular weight of the polymers. Since therapeutic macromolecules require a slow renal excretion and a sufficiently long stay in circulation (to facilitate tumor accumulation), large HPMA-ran-LMA copolymers seem to be most suitable for future development as drug carriers.