방사선의학 웹진

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Abstract
Most nanoparticles show much higher uptake in mononuclear phagocyte system (MPS) organs than in tumors, which has been a long-lasting dilemma in nanomedicine. Here, we report an imaging strategy that selectively decreases MPS organ uptakes by utilizing the differential esterase activity in tumors and other organs. When an esterase-labile radiotracer loaded liposome was injected into the body, radioactivity was rapidly excreted from the liver and spleen after breakage of the ester bond by esterase. However, the lipophilic radiotracer delivered to the tumor remained in the tumor with minimal bond cleavage. The underlying mechanism was fully characterized in vitro and in vivo in colon tumor models. As a proof of concept, the liposomal radiotracer was further optimized for the early detection of pancreatic cancer. The folate-coated liposomal radiotracer showed highly selective tumor uptake. At 4 h postinjection, a pancreatic tumor a few millimeters in size was unambiguously visualized in orthotopic tumor models by PET imaging. At 24 h, an exceptionally high tumor-to-background ratio was achieved, enabling the visualization of tumors alone with minimal background noise. More than 9% of the total radioactivity was found in the tumor. Utilizing our imaging strategy, various tumor imaging agents can be developed for sensitive detection with ultrahigh contrast.

Affiliations

Woonghee Lee  1 , Gwang Il An  2 , Hyun Park  2 , Swarbhanu Sarkar  1 , Yeong Su Ha  1 , Phuong Tu Huynh  1 , Abhinav Bhise  1 , Nikunj Bhatt  1 , Heesu Ahn  1 , Darpan N Pandya  1 , Jung Young Kim  2 , Seokho Kim  3 , Eunsung Jun  4   5 , Song Cheol Kim  4 , Kyo Chul Lee  2 , Jeongsoo Yoo  1
1 Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
2 Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
3 Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea.
4 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
5 Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul 05505, Republic of Korea.