Recent Development of Radiolabeled Nanoparticles for PET Imaging

Research Article

Austin J Nanomed Nanotechnol. 2014;2(2): 1016.

Recent Development of Radiolabeled Nanoparticles for PET Imaging

Yan Xing1,2, Jinhua Zhao 2,*, Xiangyang Shi3, Peter S. Conti1, Kai Chen1,*

1Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, USA

2Department of Nuclear Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, China

3College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, China

*Corresponding author: Kai Chen, Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC103, Los Angeles, CA 90033, USA

Received: January 06, 2014; Accepted: March 17, 2014; Published: March 24, 2014


Nanoparticles bearing unique properties have gained great interest in biomedical applications. PET imaging can provide functional and molecular information on the biological events, offering the abilities to improve disease detection, therapeutic monitoring, and treatment efficacy. Nanoparticles labeledwith a positron emitter can be used for PET imaging to noninvasively monitor their path and fate in living subjects. In the last few years, significant breakthrough has been made toward the application of various radiolabeled nanoparticles for PET imaging. This review briefly summarizes the recent development of radiolabeled nanoparticles, including organic and inorganic nanoparticles, for PET imaging in cancer and cardiovascular diseases. The major challenges involved in the translation of radiolabeled nanoparticles to the clinic PET are also discussed. It is expected that novel radiolabeled nanoparticles with PET along with other imaging modalities will afford accurate and precise assessment of biological signatures in a real–time manner and thus improve disease management.

Keywords: Radiolabeled nanoparticles; PET imaging; Cancer; Cardiovascular disease


PET, Positron Emission Tomography; CT, Computed Tomography; MRI, Magnetic Resonance Imaging; NIRF, Near Infrared Fluorescence; NPs, Nanoparticles; EPR, Enhanced Permeability and Retention; CNTs, Carbon Nanotubes; SWCNTs, Single–Walled Carbon NanoTubes; MWCNTs, Multi–Walled Carbon Nanotubes; GO, Graphene Oxide; PEG, Polyethylene Glycol; GNPs, Gold Nanoparticles; QDs, Quantum Dots; IO, Iron xide; SPIO, SuperParamagnetic Iron Oxide; USPIO, Ultra–Small superParamagnetic Iron Oxide; RGD, Arg–Gly–Asp; pi, Postinjection; PBS, Phosphate Buffered Saline; PDGFR, Platelet–Derived Growth Factor Receptor; PDGFB, Platelet–Derived Growth factor B;GEMM, Genetically Engineered Mouse Model; PEO, Polyethylene Oxide; DOTA, 1, 4, 7, 10–tetraazacyclododecane–1, 4, 7, 10–tetraacetic acid; NOTA, 1,4,7–triazacyclononane–1,4,7–triacetic acid; DTPA, Dianhydridediethylenetriaminepentaacetic acid; CLIO, Cross–linked Iron Oxide; HSA, Human Serum Albumin; MPS, Mononuclear Phagocytic System


Nanoparticles (NPs)usually refer to particles of sizes smaller than 100 nm [1]. A number of materials, including carbon, lipids, metals, metal oxides, polymers, silicates, and biomolecules can be prepared as nanoparticles with different shapes, such as spheres, cylinders, platelets, and tubes. Because of their unique physical properties, NPs demonstrate marvelous interactions with biomolecules. For instance, NPs with diameters ranging from 10 to 100 nm can extravasate hrough the endothelial cell layers and interact with the cell structures of various tissues due to the enhanced permeability and retention (EPR) effect. In addition, the large surface area to volume ratio renders NPs with the ability to be readily loaded with a variety of diagnostic and/or therapeutic agents as theranostics for disease detection and treatment.

Molecular imaging can be defined as in vivo visualization, characterization and measurement of biological processes at the molecular and cellular levels [2,3]. Up to date, various molecular imaging modalities have been exploited for disease diagnosis, stratification, and treatment assessment [4]. Molecular imaging nvolves administration of imaging probes and detection of signals roduced from the probes [5]. Molecular imaging probes labeled with the prominent positron–emitter offer the opportunity to noninvasively monitor their path and fate in the living subject by the scintigraphic technique, positron emission tomography (PET). As an in vivo pharmacological imaging tool with the capability of providing highly sensitive and quantitative information, PET will play an increasingly important role in earlier disease detection and improved therapeutic decision making [6]. Due to their unique physical properties, NPs can be radiolabeled with positron emitting isotopes for noninvasively deciphering the biological events, such as tumor receptor levels and tumor enzyme activities [7]. Therefore, PET imaging using radiolabeled NPs has been attracting great interest in preclinical research and clinical setting [8,9]. However, the construction of radiolabeled nanoparticles is not trivial. Several key issues need to be taken into account, such as how to choose the appropriate isotopes and nanoparticles, what chemical reactions can be utilized to improve the labeling efficiency, and how to functionalize the nanoparticles to achieve the best contrast for PET imaging. Although several excellent reviews have been published recently [9–11], very few of them focused on the construction method of radiolabeled nanoparticles and the key issues involved in the translation of radiolabeled nanoparticles to the clinic PET.

In this review, we address advantages and challenges in developing PET imaging probes by using different types of nanoparticles, and summarize the recent advances in the applications of radiolabeled nanoparticles for PET imaging of cancer and cardiovascular diseases.

Construction of PET radionuclide labelednanoparticles

In order to obtain optimal imaging outcome, appropriate PET isotope and radiolabeling strategy must be carefully taken into consideration. The positron emitting isotopes can be generally classified into two classes according to their decay time. Short–lived positron emitters include 11MC (t1/2 = 20 min), 15O (t1/2 = 2 min), 18F(t1/2 = 109.7min), 68Ga (t1/2 = 67.7 min), 64Cu (t1/2 = 12.7 hr), and 76Br (t1/2 = 16.2 hr) with half–lives from several minutes to hours. Typical long–lived positron emitters include 89Zr and 124I with half–lives of 3.2 days and 4.2 days, respectively [12]. Among these radionuclides, 64Cu (t1/2 = 12.7 h; β+ 655 keV, 17.8%) has attracted considerable interest in the construction of radiolabeled NPs because of its favorable decay half–life, low β+ energy, and commercial availability [13,14]. The PET radioisotope can be attached to the payload encapsulated inside the nanoparticle [15]. The radionuclide can also be conjugated directly on the surface of nanoparticle core through various labeling approaches, including direct labeling (nucleophilic or electrophilic reaction), indirect labeling (through prosthetic group), and coordination chemistry [7]. Among these approaches, complexation reactions of adiometal ions with chelates through coordination chemistry have been widely used. As compared to radio–halogenation, this approach has simpler chemistry and the production kits are usually commercially available. For example, 1, 4, 7, 10–tetraazacyclododecane–1, 4, 7, 0–tetraacetic acid (DOTA) is one of commonly used chelates for the construction of radiometal–labeled PET nanoparticles [16]. The typical radionuclides for PET imaging and the common radiolabeling methods [17–20] are summarized in Table 1.