title: Molecular imaging using nanoparticle quenchers of Cerenkov luminescence.
abstract: Cerenkov luminescence (CL) imaging is an emerging technique that collects the visible photons produced by radioisotopes. Here, molecular imaging strategies are investigated that switch the CL signal off. The noninvasive molecularly specific detection of cancer is demonstrated utilizing a combination of clinically approved agents, and their analogues. CL is modulated in vitro in a dose dependent manner using approved small molecules (Lymphazurin), as well as the clinically approved Feraheme and other preclinical superparamagnetic iron oxide nanoparticles (SPIO). To evaluate the quenching of CL in vivo, two strategies are pursued. [(18) F]-FDG is imaged by PET and CL in tumors prior to and following accumulation of nanoparticles. Initially, non-targeted particles are administered to mice bearing tumors in order to attenuate CL. For targeted imaging, a dual tumor model (expressing the human somatostatin receptor subtype-2 (hSSTr2) and a control negative cell line) is used. Targeting hSSTr2 with octreotate-conjugated SPIO, quenched CL enabling non-invasive distinction between tumors' molecular expression profiles is demonstrated. In this work, the quenching of Cerenkov emissions is demonstrated in several proof of principle models using a combination of approved agents and nanoparticle platforms to provide disease relevant information including tumor vascularity and specific antigen expression.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology and Radiological Sciences, The Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Daniel L J
authors.initials: DL
authors.lastname: Thorek
authors.forename: Sudeep
authors.initials: S
authors.lastname: Das
authors.forename: Jan
authors.initials: J
authors.lastname: Grimm
mesh_terms: D000818:Animals; D004396:Coloring Agents / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D049449:Luminescence; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D036103:Nanotechnology / Q000379:methods; D009368:Neoplasm Transplantation; D017481:Receptors, Somatostatin / Q000737:chemistry; D012394:Rosaniline Dyes / Q000737:chemistry; D013053:Spectrophotometry
chemical_list: D004396:Coloring Agents; D005290:Ferric Compounds; D017481:Receptors, Somatostatin; D012394:Rosaniline Dyes; C000499:ferric oxide; C025484:iso-sulfan blue; C093733:somatostatin receptor 2
keywords: Cerenkov luminescence; activatable imaging; molecular targeting; quenching nanoparticles