68Ga[Ga]-, 111In[In]-oxine: a novel strategy of in situ radiolabeling of HPMA-based micelles.

Polymeric micelles are of increasing interest as drug delivery vehicles since they can accumulate in tumor tissue through EPR effect and deliver their hydrophobic cargo. The pharmacology can be visualized and quantified noninvasively by molecular imaging techniques. Here, a novel, fast and efficient technique for radiolabeling various HPMA-LMA based micellar aggregates with hydrophobic oxine-complexes of the trivalent radiometals 68Ga and 111In was investigated. The radiometal-oxine complexes resemble the hydrophobic drug 111In[In]-oxine considered for the diagnosis of infection and inflammation. Promising in vitro stability lead to in vivo evaluation in healthy mice in terms of quantitative ex vivo organ distribution. The results show that while the hydrophobic radiometal-oxine complexes were safely encapsulated in aqueous saline, they left the polymeric micelles slowly in contact with blood serum and more rapidly in vivo. Due to the similarity between the radiometal complexes and hydrophobic drugs transported in the polymeric micelles this has significant implications for further strategies on transport mechanisms of hydrophobically encapsulated drugs.