Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe
By Evan Phillips, Oula Peñate-Medina, P. Zanzonico, R. Carvajal, Pauliah Mohan, Y. Ye, J. Humm, M. Gönen, H. Kalaigian, H. Schöder and 4 more. Science Translational Medicine, 2014
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Ultrasmall inorganic hybrid optical-PET imaging particles were found to be safe and physiologically stable in patients with melanoma. First-in-Human Nanoparticles for Molecular Cancer Imaging Molecular targeting and nanotechnology together have a promising future in cancer imaging. Tiny particles can be coated with antibodies or peptides to target a molecule specific to cancer, improving diagnostic accuracy and patient stratification. Yet, these decorated nanoparticles have been slow in making it to clinical trials. Now, Phillips and colleagues describe the translation of ultrasmall (<10 nm) inorganic nanoparticles, called “C dots,” from animals to patients. The C dots comprised a silica shell encapsulating the fluorescent Cy5 dye, coated with a polymer called poly(ethylene glycol) (PEG), and then decorated with the integrin-targeting, radiolabeled peptide 124I-cRGDY. With the Cy5 and 124I, the particle could be imaged by optical methods (fluorescence) and by positron emission tomography (PET). The goal of this first-in-human study was to evaluate pharmacokinetics and biodistribution of the 124I-cRGDY–PEG–C dots when injected systemically, with molecular targeting and cancer imaging as a secondary effort. The authors found that the nanoparticles were not toxic in a small group of five patients with metastatic melanoma and that the particles were excreted intact via the kidneys and bladder (by contrast, larger or uncoated particles often get lodged in the liver). In some patients, the C dots were visible in the tumor region by PET imaging. Many more patients will need to be studied to confirm lack of toxicity and to optimize tumor targeting, but this first demonstration in people suggests that such ultrasmall nanoparticles can be tested in people, heralding in a new era of molecular cancer imaging. 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 124I for positron emission tomography (PET) imaging and modified with cRGDY peptides for molecular targeting. 124I-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 124I-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.
Subfields: Biomaterials, Biomedical Engineering, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f4fb15a51e9e2d14ce8e1a6eefc7f6bd561b9022
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Citations in the corpus
- Nanoparticles in the clinic (2016, methodology): “, Cornell Dots), where timedependent biodistribution and subsequently organ-specific accumulations in specific patients can be determined and analyzed (Figures 3a–3c).(92) Unfortunately, nanoparticles not designed for imaging will find it difficult to achieve understanding of their biological fate.”
- Current Challenges and Opportunities in Treating Glioblastoma (2018, background): “In addition to liposomal-based systems, inorganic nanocarriers such as Cornell Dots; silica NPs conjugated with cyclic arginine–glycine–aspartic acid (cRGDY) peptides; and NU-0129, small gold NPs attached to spherical nucleic acids targeted for BCL2L12, are being tested (Phillips et al., 2014).”
- Ultrasmall copper-based nanoparticles for reactive oxygen species scavenging and alleviation of inflammation related diseases (2020, positive): “…with ultrasmall size (hydrodynamic diameter 5.5 nm) shall be designed because this kind of nanomaterials will have high catalytic activity due to the relatively large surface to volume ratios 20 and rapid renal clearance because they can pass through the glomerular capillary wall in kidney 21,22 .”