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: Evan Phillips, Oula Penate-Medina, Pat B Zanzonico, Richard D Carvajal, Pauliah Mohan, Yunpeng Ye, John Humm, Mithat Gönen, Hovanes Kalaigian, Heiko Schöder, H William Strauss, Steven M Larson, Ulrich Wiesner, Michelle S Bradbury
• Journal: Science translational medicine (Sci Transl Med) Vol. 6 Issue 260 Pg. 260ra149 (Oct 29 2014) ISSN: 1946-6242 [Electronic] United States
• PMID: 25355699 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Association for the Advancement of Science.

Chemical References

• Molecular Probes

Topics

• Adult
• Aged
• Clinical Trials as Topic
• Female
• Humans
• Male
• Middle Aged
• Molecular Probes
• Nanoparticles
• Optics and Photonics
• Positron-Emission Tomography
• Research Design