Tag Archives: Robert J. Nickles

Better bioimaging accuracy with direct radiolabeling of nanomaterials

Even I can tell the image is improved when the chelator is omitted,

Courtesy: Wiley

A Feb. 9, 2017 news item on phys.org describes a new, chelator-free technique for increased bioimaging accuracy,

Positron emission tomography (PET) plays a pivotal role for monitoring the distribution and accumulation of radiolabeled nanomaterials in living subjects. The radioactive metals are usually connected to the nanomaterial through an anchor, a so-called chelator, but this chemical binding can be omitted if nanographene is used, as American scientists report in the journal Angewandte Chemie. The replacement of chelator-based labeling by intrinsic labeling significantly enhances the bioimaging accuracy and reduces biases.

A Feb 9, 2017Wiley press release (also on EurekAlert), which originated the news item, provides more detail,

Nanoparticles are very promising substances for biodiagnostics (e.g., detecting cancerous tissue) and biotherapy (e.g., destroying tumors by molecular agents), because they are not as fast [sic] metabolized as normal pharmaceuticals and they particularly enrich [sic] in tumors through an effect called enhanced permeability and retention (EPR). Chelators, which have a macrocyclic structure, are used to anchor the radioactive element (e.g., copper-64) onto the nanoparticles’ surface. The tracers are then detected and localized in the body with the help of a positron emission tomography (PET) scanner. However, the use of a chelator can also be problematic, because it can detach from the nanoparticles or bias the imaging. Therefore, the group of Weibo Cai at University of Wisconsin-Madison, USA, sought for chelator-free solutions—and found it in nanographene, one of the most promising substances in nanotechnology.

Nanographene offers the electronic system to provide special binding electrons for some transition metal ions. “π bonds of nanographene are able to provide the additional electron to stably incorporate the 64Cu2+ acceptor ions onto the surface of graphene,” the authors wrote. Thus, it was possible to directly and stably attach the copper isotope to reduced graphene oxide nanomaterials stabilized by poly(ethylene glycol) (PEG), and this system was used for several bioimaging tests including the detection of tumors in mice.

After injection in the mouse model, the scientists observed long blood circulation and high tumor uptake. “Prolonged blood circulation of 64Cu-RGO-PEG […] induced a prompt and persistent tumor uptake via EPR effect,” they wrote. Moreover, the directly radiolabeled nanographene was readily prepared by simply mixing both components and heating them. This simple chelator-free, intrinsically labeled system may provide an attractive alternative to the chelator-based radiolabeling, which is still the “gold standard” in bioimaging.

Here’s a link to and a citation for the paper,

Chelator-Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation by Sixiang Shi, Cheng Xu, Dr. Kai Yang, Shreya Goel, Hector F. Valdovinos, Dr. Haiming Luo, Emily B. Ehlerding, Dr. Christopher G. England, Dr. Liang Cheng, Dr. Feng Chen, Prof. Robert J. Nickles, Prof. Zhuang Liu, and Prof. Weibo Cai. Angewandte Chemie International Edition DOI: 10.1002/anie.201610649 Version of Record online: 7 FEB 2017

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

A nanoparticle for a medical imaging machine that doesn’t exist yet

Researchers at the University of Buffalo (New York state) have created a nanoparticle that can be detected by six imaging devices according to a Jan. 20, 2015 news item on ScienceDaily,

It’s technology so advanced that the machine capable of using it doesn’t yet exist.

Using two biocompatible parts, University at Buffalo researchers and their colleagues have designed a nanoparticle that can be detected by six medical imaging techniques:

• computed tomography (CT) scanning;

• positron emission tomography (PET) scanning;

• photoacoustic imaging;

• fluorescence imaging;

• upconversion imaging; and

• Cerenkov luminescence imaging.

The advantages are obvious should somebody, somewhere create a hexamodal (aka, multimodal, aka hypmodal) sensing device capable of exploiting the advantages of this nanoparticle as the researchers hope.

A Jan. 20, 2015 University of Buffalo news release (also on EurekAlert) by Charlotte Hsu, which originated the news item, describes the ideas underlying the research,

This kind of “hypermodal” imaging — if it came to fruition — would give doctors a much clearer picture of patients’ organs and tissues than a single method alone could provide. It could help medical professionals diagnose disease and identify the boundaries of tumors.

“This nanoparticle may open the door for new ‘hypermodal’ imaging systems that allow a lot of new information to be obtained using just one contrast agent,” says researcher Jonathan Lovell, PhD, UB assistant professor of biomedical engineering. “Once such systems are developed, a patient could theoretically go in for one scan with one machine instead of multiple scans with multiple machines.”

When Lovell and colleagues used the nanoparticles to examine the lymph nodes of mice, they found that CT and PET scans provided the deepest tissue penetration, while the photoacoustic imaging showed blood vessel details that the first two techniques missed.

Differences like these mean doctors can get a much clearer picture of what’s happening inside the body by merging the results of multiple modalities.

A machine capable of performing all six imaging techniques at once has not yet been invented, to Lovell’s knowledge, but he and his coauthors hope that discoveries like theirs will spur development of such technology.

The news release also offers a description of the nanoparticles,

The researchers designed the nanoparticles from two components: An “upconversion” core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.

Each part has unique characteristics that make it ideal for certain types of imaging.

The core, initially designed for upconversion imaging, is made from sodium, ytterbium, fluorine, yttrium and thulium. The ytterbium is dense in electrons — a property that facilitates detection by CT scans.

The PoP wrapper has biophotonic qualities that make it a great match for fluorescence and photoacoustic imagining. The PoP layer also is adept at attracting copper, which is used in PET and Cerenkov luminescence imaging.

“Combining these two biocompatible components into a single nanoparticle could give tomorrow’s doctors a powerful, new tool for medical imaging,” says Prasad, also a SUNY Distinguished Professor of chemistry, physics, medicine and electrical engineering at UB. “More studies would have to be done to determine whether the nanoparticle is safe to use for such purposes, but it does not contain toxic metals such as cadmium that are known to pose potential risks and found in some other nanoparticles.”

“Another advantage of this core/shell imaging contrast agent is that it could enable biomedical imaging at multiple scales, from single-molecule to cell imaging, as well as from vascular and organ imaging to whole-body bioimaging,” Chen adds. “These broad, potential capabilities are due to a plurality of optical, photoacoustic and radionuclide imaging abilities that the agent possesses.”

Lovell says the next step in the research is to explore additional uses for the technology.

For example, it might be possible to attach a targeting molecule to the PoP surface that would enable cancer cells to take up the particles, something that photoacoustic and fluorescence imaging can detect due to the properties of the smart PoP coating. This would enable doctors to better see where tumors begin and end, Lovell says.

The researchers have provided two images,

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core. Credit: Jonathan Lovell

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.
Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging. Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging.
Credit: Jonathan Lovell

Here’s a link to and a citation for the paper,

Hexamodal Imaging with Porphyrin-Phospholipid-Coated Upconversion Nanoparticles by James Rieffel, Feng Chen, Jeesu Kim, Guanying Chen, Wei Shao, Shuai Shao, Upendra Chitgupi, Reinier Hernandez, Stephen A. Graves, Robert J. Nickles, Paras N. Prasad, Chulhong Kim, Weibo Cai, and Jonathan F. Lovell. Advanced Materials DOI: 10.1002/adma.201404739 Article first published online: 14 JAN 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This article is behind a paywall.