Urokinase injection-triggered clearance enhancement of a 4-arm PEG-conjugated 64Cu-bombesin analog tetramer: A novel approach for the improvement of PET imaging contrast

Publication date: 10 July 2018 Source:International Journal of Pharmaceutics, Volume 545, Issues 1–2 Author(s): Kazushi Matsumura, Maki Zouda, Yasuhiro Wada, Fumiyoshi Yamashita, Mitsuru Hashida, Yasuyoshi Watanabe, Hidefumi Mukai Radiolabeled antibodies, polyethylene glycol-conjugated (PEGylated) peptides, liposomes, and other materials were investigated as positron-emission tomography (PET) probes. These substances accumulate in tumors but often remain too long in circulation. We investigated the combination of intravenous urokinase injection and its substrate linker as a triggered radioisotope clearance enhancement system to improve imaging contrast. To this end, we synthesized a four-arm PEGylated 64Cu-bombesin analog tetramer with a urokinase substrate linker. In mouse blood, it was almost perfectly cleaved and degraded into smaller radioactive fragments in vitro with urokinase (≥20,000 IU/mL). In mouse blood circulation, ∼50–65% of the probe was rapidly degraded after the urokinase injection and the radioactive fragments were eliminated mainly from the kidney. In contrast, tumor radioactivity levels did not change, and therefore, the tumors were clearly visualized. The tumor/blood ratio, an indicator of imaging contrast, increased 2.5 times, while elimination of the radioisotope from the blood was enhanced. This approach has the potential to improve imaging contrast using various PET probes. It could also shorten the time required to obtain sufficient...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research