The targeted delivery of radiopharmaceuticals to tumour sites has long been viewed as a method to improve imaging quality by virtue of improved tumour-to-background ratios and reduced side effects from radiotherapy by decreasing the radiation dose to other organs and tissue. One proposed approach to achieve this targeting is to employ functional nanoparticle platforms that exploit the enhanced permeation and retention (EPR) effect present in tumours with leaky vasculature. One family of functional nanoparticles, so-called star polymers, offer the opportunity to engineer nanoparticles with highly controlled microstructures and sizes through the use of controlled radical polymerisation.

While the methods for preparing complex and innovative star polymers is well established, little is known about the biopharmaceutical behaviour of star polymers and their metabolic fragments. To investigate this question a series of star polymers were prepared using RAFT polymerisation techniques incorporating non-biodegradable and biodegradable linkages, specifically disulfide and acetal groups, and the NOTA chelator for radiometal complexation have been prepared. The star polymers have been successfully radiolabelled with both copper-64 (⁶⁴Cu) and gallium-67 (⁶⁷Ga), (Figure 1).

The stability of the radiolabelled star polymers was examined in formulation (PBS), acidic media to mimic lysosomes (acetal breakdown), reducing media (disulphide reduction) and in human serum. Size exclusion chromatography (SEC) HPLC methods were successfully developed to quantify the formation of breakdown products, (Figure 2). Additionally, simple methods were developed to remove the bulk of serum proteins allowing for quantification of serum protein binding and metabolite analysis.

We have developed techniques for the rapid assessment of star polymers stability, providing feedback for the next generation of nanoparticles and the identification of star polymer metabolites extracted from in vivo samples. Future work will examine the correlation between these results and biopharmaceutical parameters determined from in vivo imaging and bio-distribution studies.