title: Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe.
abstract: A first-in-human clinical trial of ultrasmall inorganic hybrid nanoparticles, "C dots" (Cornell dots), in patients with metastatic melanoma is described for the imaging of cancer. These renally excreted silica particles were labeled with (124)I for positron emission tomography (PET) imaging and modified with cRGDY peptides for molecular targeting. (124)I-cRGDY-PEG-C dot particles are inherently fluorescent, containing the dye, Cy5, so they may be used as hybrid PET-optical imaging agents for lesion detection, cancer staging, and treatment management in humans. However, the clinical translation of nanoparticle probes, including quantum dots, has not kept pace with the accelerated growth in minimally invasive surgical tools that rely on optical imaging agents. The safety, pharmacokinetics, clearance properties, and radiation dosimetry of (124)I-cRGDY-PEG-C dots were assessed by serial PET and computerized tomography after intravenous administration in patients. Metabolic profiles and laboratory tests of blood and urine specimens, obtained before and after particle injection, were monitored over a 2-week interval. Findings are consistent with a well-tolerated inorganic particle tracer exhibiting in vivo stability and distinct, reproducible pharmacokinetic signatures defined by renal excretion. No toxic or adverse events attributable to the particles were observed. Coupled with preferential uptake and localization of the probe at sites of disease, these first-in-human results suggest safe use of these particles in human cancer diagnostics.
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Phillips
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Oula
authors.initials: O
authors.lastname: Penate-Medina
authors.affiliation: Department of Medical Physics, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.affiliation: Department of Medicine, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Pauliah
authors.initials: P
authors.lastname: Mohan
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Medical Physics, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: John
authors.initials: J
authors.lastname: Humm
authors.affiliation: Department of Epidemiology and Biostatistics, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Medical Physics, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Hovanes
authors.initials: H
authors.lastname: Kalaigian
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Heiko
authors.initials: H
authors.lastname: Schöder
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: H William
authors.initials: HW
authors.lastname: Strauss
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.affiliation: Department of Materials Science and Engineering, Cornell University, 330 Bard Hall, Ithaca, NY 14853, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wiesner
authors.affiliation: Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA. bradburm@mskcc.org ubw1@cornell.edu.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Bradbury
mesh_terms: D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015335:Molecular Probes; D053758:Nanoparticles; D055095:Optics and Photonics; D049268:Positron-Emission Tomography; D012107:Research Design
chemical_list: D015335:Molecular Probes