Rapid and scalable formulation and radiolabeling of phthalocyanine-based nanoparticles as a platform for targeted PET

R.K. Prud'homme, L.Z. Wang, H.D. Lu, B.K. Wilson, S.A. McManus, P.K. Padakanti, A. Alavi, R.H. Mach
Princeton University,
United States

Keywords: nanoparticles, PET, diagnostics

Summary:

Across all cancer types, diagnostic promptness and accuracy remains the deciding factor for patient prognosis. Positron emission tomography (PET) is along the most sensitive of imaging modalities but requires localization of radionuclides to the targeted imaging site. To this end, targeted nanoparticles can be used to both localize the PET signal and drastically improve sensitivity by clustering thousands of contrast agents in one place. Use of these nanoparticle contrast agents, however, is limited by the lack of a fast and clinically relevant formulation and radiolabeling method, either requiring excessive surface modification or harsh loading conditions. Additionally, commonly used short-lived positron emitters, such as 18F, limits PET imaging to only institutions that have an on-site cyclotron. We here present the use of Flash Nanoprecipitation (FNP), a continuous and scalable self-assembly process, to form phthalocyanine encapsulated polymeric nanoparticles (NPs). When incubated in a solution of 64Cu, a long half-life positron emitter, the phthalocyanine core acts as a sink to rapidly chelate copper in a stable and irreversible manner, generating PET active nanoparticles. Absorbance changes of the phthalocyanine dye NPs incubated with non-radioactive copper provides a simple method to track the chelation progress and generate a reaction rate model to optimize reaction conditions without excessive radiation exposure. At the mild conditions of pH 5.5 and 37℃, phthalocyanine nanoparticles could chelate 64Cu with 98% efficiency after 3 hours and retained 90% 64Cu even after incubation with ethylenediaminetetraacetic acid for 12 hours. These results were shown be to consistent with the previous reaction model generated from non-radioactive copper. Core radiolabeling of preformed nanoparticles in this way allows for compartmentalization of NP targeting properties on its surface from imaging properties in the core. Thus, the development and optimization of this rapid and facile nanoparticle formulation and radiolabeling process facilitates adaptation of nanoparticle PET contrast agents for more sensitive and specific cancer diagnostics.