Molecular biology

Nanoparticle

Biotechnology

Biology

Materials science

Cancer research

Biochemistry

Furin

Intracellular

In vivo

Nanotechnology

In vitro

Enzyme

Pet imaging

Medicine

Chemistry

Nuclear medicine

Biophysics

Positron emission tomography

Analytical Chemistry

Positron-emission tomography (PET) is routinely used in the clinic for tumor imaging with ultrahigh sensitivity, but tumor-targeted PET imaging probes are quite few. In this work, we rationally designed a furin-responsive radiotracer Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Lys(DOTA-68Ga)-CBT (CBT-68Ga) and demonstrated that coinjection of the radiotracer with its cold analogue CBT-Ga instructed the formation of 68Ga nanoparticles in furin-overexpressing MDA-MB-468 cancer cells, which significantly enhanced microPET imaging of the tumor in vivo. In vitro results showed that CBT-Ga subjected to furin-initiated CBT-Cys condensation reaction and self-assembly to form the nanoparticles CBT-Ga-NPs with an average diameter of 258.3 nm. In vivo microPET imaging results indicate that the mice coinjected with CBT-68Ga and CBT-Ga, which warrants 68Ga nanoparticle formation in their MDA-MB-468 tumors, had a tumor/liver ratio 9.1-fold of that of the mice only injected with CBT-68Ga. We envisioned that, by replacing the RVRR substrate of CBT-68Ga with other enzyme-specific ones and using the strategy of intracellular nanoparticle formation, a series of radioactive probes could be developed for more sensitive and precise tumor microPET imaging in the near future.

Furin-Guided Intracellular <sup>68</sup>Ga Nanoparticle Formation Enhancing Tumor MicroPET Imaging

Furin-Guided Intracellular 68Ga Nanoparticle Formation Enhancing Tumor MicroPET Imaging

Furin-Guided Intracellular ⁶⁸Ga Nanoparticle Formation Enhancing Tumor MicroPET Imaging