Ultrasmall [64Cu]Cu Nanoclusters for Targeting Orthotopic Lung Tumors Using Accurate Positron Emission Tomography Imaging

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Abstract

Positron emission tomography (PET) imaging has received special attention owing to its higher sensitivity, temporal resolution, and unlimited tissue penetration. The development of tracers that target specific molecules is therefore essential for the development and utility of clinically relevant PET procedures. However, (64)Cu as a PET imaging agent generally has been introduced into biomaterials through macrocyclic chelators, which may lead to the misinterpretation of PET imaging results due to the detachment and transchelation of (64)Cu. In this study, we have developed ultrasmall chelator-free radioactive [(64)Cu]Cu nanoclusters using bovine serum albumin (BSA) as a scaffold for PET imaging in an orthotopic lung cancer model. We preconjugated the tumor target peptide luteinizing hormone releasing hormone (LHRH) to BSA molecules to prepare [(64)Cu]CuNC@BSA-LHRH. The prepared [(64)Cu]Cu nanoclusters showed high radiolabeling stability, ultrasmall size, and rapid deposition and diffusion into tumor, as well as predominantly renal clearance. [(64)Cu]CuNC@BSA-LHRH showed 4 times higher tumor uptake compared with that of [(64)Cu]CuNC@BSA by analyzing the (64)Cu radioactivity of tissues via gamma counting. The PET imaging using [(64)Cu]Cu nanoclusters as tracers showed more sensitive, accurate, and deep penetration imaging of orthotopic lung cancer in vivo compared with near-infrared fluorescence imaging. The nanoclusters provide biomedical research tools for PET molecular imaging.

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