18F-Radiolabeling, Preliminary Evaluation of Folate-pHPMA Conjugates via PET

The synthesis of a 10.5 kDa and a 52.5 kDa polymer, based on pHPMA functionalized with tyramine for 18F‐labeling and a folate derivative as targeting moiety, is reported. FCS studies are conducted using Oregon Green‐labeled conjugates. No aggregation is observed for the 10.5 kDa conjugate, but strong aggregation for the 52.5 kDa conjugate. In vivo studies are conducted using Walker‐256 mammary carcinoma model to determine body distribution as function of size and especially targeting unit. These in vivo studies show a higher short time (2 h) accumulation for both conjugates in the tumor than for untargeted pHPMA, confirmed by blockade studies. The 10.5 kDa polymer accumulates with 0.46% ID g−1 and the 52.5 kDa polymer with 0.28% ID g−1 in the tumor after 2 h, demonstrating the potential of the folate‐targeting concept. For two new 18F‐labeled pHPMA copolymers, which are functionalized with folate units, active targeting can be proved in vivo (Walker carcinoma) by blockade studies.