Biodistribution of 68/67Ga-Radiolabeled Sphingolipid Nanoemulsions by PET and SPECT Imaging

Abstract

Background and Purpose Non-invasive imaging methodologies, especially nuclear imaging techniques, have undergone an extraordinary development over the last years. Interest in the development of innovative tracers has prompted the emergence of new nanomaterials with a focus on nuclear imaging and therapeutical applications. Among others, organic nanoparticles are of the highest interest due to their translational potential related to their biocompatibility and biodegradability. Our group has developed a promising new type of biocompatible nanomaterials, sphingomyelin nanoemulsions (SNs). The aim of this study is to explore the potential of SNs for nuclear imaging applications. Methods Ready-to-label SNs were prepared by a one-step method using lipid derivative chelators and characterized in terms of their physicochemical properties. Stability was assessed under storage and after incubation with human serum. Chelator-functionalized SNs were radiolabeled with 67 Ga and 68 Ga, and the radiochemical yield (RCY), radiochemical purity (RCP) and radiochemical stability (RCS) were determined. Finally, the biodistribution of 67/68 Ga-SNs was evaluated in vivo and ex vivo. Results Here, we describe a simple and mild one-step method for fast and efficient radiolabeling of SNs with 68 Ga and 67 Ga radioisotopes. In vivo experiments showed that 67/68 Ga-SNs can efficiently and indistinctly be followed up by PET and SPECT. Additionally, we proved that the biodistribution of the 67/68 Ga-SNs can be conveniently modulated by modifying the surface properties of different hydrophilic polymers, and therefore the formulation can be further adapted to the specific requirements of different biomedical applications. Conclusion This work supports 67/68 Ga-SNs as a novel probe for nuclear imaging with tunable biodistribution and with great potential for the future development of nanotheranostics.

PEGylation Effects on the Interaction of Sphingomyelin Nanoemulsions with Serum Albumin: A Thermodynamic Investigation

“…Previous reports showed that plain SNs composed by a VitE:SM (1:0.1) mass ratio present high potential for targeted drug delivery, gene therapy, and molecular imaging applications. [ 4,32–36 ] In addition, a narrow distribution together a size below 100 nm and a negative zeta potential were reported for the SNs (1:0.1) formulations. [ 6 ] Therefore, we have selected for the thermodynamic study this basic formulation to evaluate how surface modifications can influence the interaction with BSA.…”

Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment

“…56,57 Previous results from our group highlight the potential of SNs for the development of new cancer therapeutics. [34][35][36][37][38] For gene therapy applications, they have already been tested for delivery of microRNA (miRNA) and pDNA upon modification with the cationic lipids DOTAP and stearylamine. 14,58 Here, we have selected putrescine, a natural polyamine presented in eukaryotic cells for which cancer cells are ravenous due to their increased metabolic activity, 26,59 as the cationic material for the development of a new type of cationic SNs 14,33,34 for cancer gene therapy applications.…”

“…In this work, we propose the incorporation of a putrescine derivative, oleamide-modified putrescine, in sphingomyelin nanosystems (SNs), previously developed by our group, 14,[33][34][35][36][37][38][39] and composed by vitamin E, a GRAS-listed excipient, 40 and sphingomyelin, one of the main components of cell membranes. 41 We aim to prove the therapeutic potential of putrescine-SNs (PSNs) that associate a plasmid encoding the apoptotic Fas Ligand (FasL) 42,43 for treating highly aggressive triple-negative breast cancer (TNBC).…”

Chemical conjugation of aptamer–sphingomyelin nanosystems and their potential as inhibitors of tumour cell proliferation in breast cancer cells

“…Additionally, their significant versatility has been proven, being able to associate with a wide variety of molecules in cancer diagnosis and therapy. 24–26…”