F-labeled modified porous silicon particles for investigation of drug delivery carrier distribution in vivo with positron emission tomography

• Published in: Molecular pharmaceutics 2011-10, Vol.8 (5), p.1799-1806
• Main Authors: Sarparanta, Mirkka, Mäkilä, Ermei, Heikkilä, Teemu, Salonen, Jarno, Kukk, Edwin, Lehto, Vesa-Pekka, Santos, Hélder A, Hirvonen, Jouni, Airaksinen, Anu J
• Format: Article
• Language: English
• Subjects: Animals; Bone and Bones - diagnostic imaging; Bone and Bones - metabolism; Chemical Phenomena; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Feasibility Studies; Fluorine Radioisotopes; Gastrointestinal Tract - diagnostic imaging; Gastrointestinal Tract - metabolism; Halogenation; Isotope Labeling; Male; Materials Testing; Microspheres; Photoelectron Spectroscopy; Positron-Emission Tomography; Rats; Rats, Wistar; Silicon Compounds - chemistry; Spectroscopy, Fourier Transform Infrared; Surface Properties; Tissue Distribution
• ISSN: 1543-8392
• DOI: 10.1021/mp2001654

Because of its biocompatibility and ability to accommodate a variety of payloads from poorly soluble drugs to biomolecules, porous silicon (PSi) is a lucrative material for the development of carriers for particle-mediated drug delivery. We report a successful direct one-step (18)F-radiolabeling of three types of PSi microparticles, thermally hydrocarbonized THCPSi, thermally oxidized TOPSi, and thermally carbonized TCPSi for the investigation of their biodistribution in vivo with positron emission tomography as part of their evaluation as carriers for particle-mediated drug delivery. FTIR and XPS characterization of the PSi materials after carrier-added (18)F/(19)F-radiolabeling reveals that depending on the material the (18)F-labeling is likely to be accomplished either by substitution for surface silyl hydrogen or silyl fluoride or by nucleophilic attack of (18)F(-) to Si-O-Si bridges. With the selected (18)F-radiolabeling method, good to excellent in vitro radiolabel stability in simulated gastric and intestinal fluids and in plasma is achieved for all the particle types studied. Finally, a preliminary evaluation of (18)F-THCPSi microparticle biodistribution in the rat gastrointestinal tract after oral administration is reported, illustrating the utility of using (18)F-radiolabeled PSi as imaging probes for PSi-based drug delivery carrier distribution in vivo.