Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 4014 2022-11-18 14:38:47 |
2 format correct -5 word(s) 4009 2022-11-21 06:30:00 | |
3 format correct Meta information modification 4009 2022-11-21 06:30:28 | |
4 format correct -3 word(s) 4006 2022-11-21 06:35:27 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Bentivoglio, V.;  Varani, M.;  Lauri, C.;  Ranieri, D.;  Signore, A. Methods for Radiolabelling Nanoparticles. Encyclopedia. Available online: https://encyclopedia.pub/entry/35311 (accessed on 30 May 2024).
Bentivoglio V,  Varani M,  Lauri C,  Ranieri D,  Signore A. Methods for Radiolabelling Nanoparticles. Encyclopedia. Available at: https://encyclopedia.pub/entry/35311. Accessed May 30, 2024.
Bentivoglio, Valeria, Michela Varani, Chiara Lauri, Danilo Ranieri, Alberto Signore. "Methods for Radiolabelling Nanoparticles" Encyclopedia, https://encyclopedia.pub/entry/35311 (accessed May 30, 2024).
Bentivoglio, V.,  Varani, M.,  Lauri, C.,  Ranieri, D., & Signore, A. (2022, November 18). Methods for Radiolabelling Nanoparticles. In Encyclopedia. https://encyclopedia.pub/entry/35311
Bentivoglio, Valeria, et al. "Methods for Radiolabelling Nanoparticles." Encyclopedia. Web. 18 November, 2022.
Methods for Radiolabelling Nanoparticles
Edit

The use of radiolabelled nanoparticles (NPs) is a promising nuclear medicine tool for diagnostic and therapeutic purposes. Thanks to the heterogeneity of their material (organic or inorganic) and their unique physical and chemical characteristics, they are highly versatile for their use in several medical applications. In particular, they have shown interesting results as radiolabelled probes for positron emission tomography (PET) imaging. The high variability of NP types and the possibility to use several isotopes in the radiolabelling process implies different radiolabelling methods that have been applied.

nanoparticles Imaging 68Ga

1. Radiolabelling with Copper-64

The use of 64Cu for the radiolabelling of NPs is raising interest in both the preclinical and the clinical field. Its long relative half-life allows one to study the biodistribution and tumor targeting of the radiolabelled NPs for up to 48 h [1]. The chemical properties of this radiometal allows the use of different chelators that can be conjugated to different molecules. However, the conjugation of them with the chelator could influence the properties of the NPs and reduce the capability of the specific targeting technique.

1.1. Direct Radiolabelling

The direct labelling of the NPs with 64Cu can be obtained with those nanomaterials that are defined as electron donors that have a high affinity with those radioisotopes that are defined as electron acceptors.
64Cu2+ ions (3d9) require an electron to have a stable electronic configuration, and for this reason, it is easy to label it with the donor nanomaterials. Shi et al. employed graphene nanomaterials as electron donors for 64Cu, thereby performing a stable direct labelling procedure without the use of BFCs. They showed that the labelling procedure is influenced by the temperature of the reaction and the concentration of the NPs. The highest labelling efficiency (LE), 75.5 ± 1.7%, was obtained with a concentration of 0.5 mg/mL−1 at 75 °C after 60 min of incubation [2].
The same method was applied to radiolabel silica NPs (SNPs), which were synthetized with the incorporation of oxygen atoms that were arranged in symmetry to be the electron donors for 64Cu. The radiolabelling occurred by simply incubating the free radioisotope at 70 °C for 60 min, and there was a final radiochemical yield (RCY) of 99% after the centrifugation of it. The RCY improves with increasing temperatures (from 4 to 70 °C), but no correlation has been shown when one is varying the pH (5.7–8.8) [3].
Other silica NPs cannot bind 64Cu stably; they dissociate rapidly under the physiological [4].
Several other metal nanomaterials can be labelled with metallic radioisotope by following the same principle of chemical affinity.
Single-well carbon nanotubes (SWCNTs) were directly radiolabelled with 64Cu using a one-step procedure by incubating the isotope and the NPs under a sonication condition for 1 h. However, the stability of the radiopharmaceutical decreased up to 50% in the serum, thereby confirming the poor stability of this radiolabelling approach for SWCNTs [5].

1.2. Radiolabelling with Bifunctional Chelators (BFCs)

DOTA is the most frequently used BFC for 64Cu labelling since after the complexation with Cu2+-ions, it forms a stable complex, thereby leaving two carboxylic functions that are free to conjugate with the NPs and other molecules. The most frequently used method radiolabelling of NPs with 64Cu is a post-synthesis process: the NPs are synthetized, coupled with the BFC, and the isotope is added at the end [6].

2. Radiolabelling with Gallium-68

68Ga is a generator-produced isotope with a relatively low cost when it is compared to the cyclotron-produced isotopes. Despite it achieving non-excellent spatial resolution imaging in PET due to the high energy of positrons on it and its very short half-life (68 min), 68Ga is a promising isotope for NP radiolabelling. Like 64Cu, 68Ga can be radiolabelled either directly or indirectly with a chelating agent, such as DOTA, NOTA, NODAGA, or other BFCs that create a very stable complex with gallium (III)-cation [7]. The widely used purification methods for 68Ga-NPs are based on solid-phase extraction (SPE) or size-exclusion chromatography (SEC). However, other methods such as ultracentrifugation have also been applied [8].

2.1. Direct Radiolabelling

The QDs with ZnS cores and a PEG-OCH3 coating (QD-OCH3) were radiolabelled with 68Ga through a cation exchange at nearly room temperature in an aqueous solution, thereby obtaining a very high LE. The QDs were doped with 68Ga by incubating 68GaCl3 in a sodium acetate buffer for 15 min at 37 °C. The NPs can subsequently be functionalized with peptides to improve their specificity [9].
Magnetite NPs (Fe3O4 MNPs) were radiolabelled without a chelator by adding a solution of sodium citrate and 68GaCl3 and incubating them at 90 °C for 40 min. Before purification, the RCY was ∼70%, as determined by radio-ITLC analysis, but after the purification, the sample showed a radiochemical purity >91% [10]. Another strategy for radiolabelling without the use of BFCs, is the core-doping of the NPs with a radioisotope using microwave-assisted heating. This method has several advantages, such as a reduced reaction time in comparison to the traditional methods, a high reproducibility, and a high LE and yield [11].
Pellico et al. radiolabelled the IONPs used this method by combining FeCl3 and dextran (to ensure a colloidal stability) with the generator eluate 68GaCl3 and heating the mixture to 100 °C (in 54 s) with microwave irradiation at 240 W for 10 min. This method turned out to be very efficient and reproducible with a high RCY, and after the purification, this was of 93.4 ± 1.8 [12].
Ligand anchoring group-mediated radiolabeling (LAGMERAL) has been demonstrated to be an efficient strategy for labeling Fe3O4 NPs. These were initially labelled with 99mTc as proof of concept, and then, they were labelled with 68Ga. This method is based on the interaction between the metal radioisotope and the diphosphonate anchoring groups of the PEG-coated NPs [13][14].

2.2. Radiolabelling with Bifunctional Chelators

PEG-modified nano-graphene sheets were conjugated with NOTA and functionalized with a TRC105 antibody for the in vivo targeting of the early stages of many tumors. NOTA was firstly attached to the NPs by binding them to PEG molecules, and this step was followed by the addition of 66Ga and its incubation for 30 min at 37 °C under a constant stirring condition [15]. 66Ga is an equivalent of 68Ga for PET use, but it has a physical half-life of 9 h, which makes more suitable for the pre-clinical kinetic studies.
Cobalt ferrite magnetic NPs that are functionalized with an aptamer-targeting under-glycosylated mucin-1 (uMUC-1) were firstly conjugated with NOTA in an NaHCO3 buffer solution while it was vortexed and mildly stirred at 4 °C, and then, radiolabelled with the 68Ga. The reaction mixture was incubated for 1 h after it was briefly vortexed for up to 24 h, and it had a high stability [16].
The IONPs were also radiolabelled with NOTA. NOTA was added into the IONPs solution and mixed for 2 h. The reaction mixture was then washed, and finally, it was purified using a PD-10 column [17].
The BFC DOTA was used for the labelling of polyamide dendrimers (PAMAM) that were conjugated with αʋβƷ receptors for the detection of tumor angiogenesis in mouse models with Ehrlich’s ascites tumors (EAT). The conjugation occurred with the addition of a DOTA-NHS ester to the dendrimer’s solution. The mixture was stirred at room temperature for 48 h, and subsequently, 68Ga was added in the solution. The reaction mixture was stirred and incubated at 90–100 °C for 15–30 min [18].
Hajiramezanali et al. conjugated SPIONs with N,N,N-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs). The conjugation with DOTA was performed using the amine groups of TMC on the surface of the NPs. It was possible to purify the final solution by centrifugating it because the functionalized NPs were precipitated. The radiolabelling procedure with 68Ga was allowed by adding a 68GaCl3 solution that had been previously eluted with 0.2 M HCl. The mixture was vortexed for 10 s and heated at 90 °C for 5 min. This method was very efficient, and it showed a radiochemical purity that was higher than 98% and a stability, in vitro in the human serum, of 92% after 120 min and of 86% after 180 min [19].
The radiolabelling of porous zirconia (ZrO2) NPs was performed using DOTA as BFC, which was successfully adsorbed on the surface of the NPs. 68Ga-radiolabelling was performed by mixing the DOTA-ZrO2 solution with 68Ga that had been previously preconditioned using AG 1-X8 resin columns at 95 °C and at a pH 4 for 20 min [20].
NODAGA is another chelator that can be used for the labelling of NPs with 68Ga. AGuIX NPs are ultrasmall rigid NPs (5 nm) that are made of polysiloxane and surrounded by gadolinium chelates. Due to their size, they are sufficiently small to escape hepatic clearance. They were functionalized with NODAGA for the following radiolabelling process with 68Ga to be performed. The labelling between the NPs and the BFC occurred by dissolving the NODAGA in DMSO, and then, it was gradually added to the AGuIX solution under a stirring condition for 5 h at room temperature. The in vivo studies showed that these NPs remain unmetabolized up to at least 60 min post-injection, thereby making them an excellent imaging agent with there being passive accumulation in the diseased area [21].
The NODAGA was used also by Lahooti et al. for the radiolabelling of ultra-small superparamagnetic iron-oxide nanoparticles (USPION) [22] and by Körhegyi et al. for the labelling of chitosan and poly-glycolic acid (PGA) NPs. In particular, the NODAGA-NHS solution, which had been previously prepared, was added in a dropwise manner to a chitosan solution, and the reaction mixture was stirred at room temperature for 24 h. The chitosan–NODAGA conjugate (CHI-NODAGA) was purified by a dialysis procedure and after the synthesis of folate-labelled PGA, the stable self-assembling NPs were produced via an ionotropic gelation process between PGA-PEG-FA and the CHI-NODAGA conjugate under a continuous stirring condition at room temperature to give an aqueous solution of the conjugated NPs. The radiolabelling was then performed by adding 68Ga into the solution and incubating it at room temperature for 15 min [23].
Hydrophilic superparamagnetic maghemite NPs, which were coated with a lipophilic organic ligand and entrapped into polymeric NPs that are made of biodegradable poly(lactic-co-glycolic acid) (PLGA) which is linked to PEG were conjugated on their surface with NODAGA through a classic peptide bond. The purification was carried out by filtering the solution. After the conjugation with NODAGA was achieved, the 68Ga eluate was added to the vial, and it was heated at 60 °C for 30 min [8].

3. Radiolabelling with Zirconium-89

Metallic radionuclides are excellent candidates for PET applications. 89Zr, thanks to its half-life of 3.3 days, has been successfully used with many biomolecules that have long circulation times, such as the antibodies for immuno-PET applications. Similarly, the NPs that have a log-plasmatic half-life may benefit from being labelled with this radioisotope.

3.1. Direct Radiolabelling

The direct labelling with 89Zr can be performed by using the chemical affinity between the isotope and the NP. In the literature, among the most significant results, the silica based-nanomaterials are often easily radiolabelled with several isotopes due to the affinity of the silanol groups with the oxophilic cations [4]. Indeed, the radiolabelling of the silica NPs with 89Zr is possible thanks to the strong interaction between the hard Lewis base (deprotonated silanol groups) and the hard Lewis acid (89Zr4+). Chen et al. used the favorable characteristics of the radiolabeled ultrasmall cRGDY-conjugated fluorescent silica NPs (C’ dots) to radiolabel them with 89Zr. As it is underlined as in this approach, is important to consider the pH and the temperature of the reaction, which should be between pH 8–9 and 50–75 °C, respectively. Indeed, a decrease in the pH (2–3) leads to a protonation of the silanol groups that cannot bind the positively charged 89Zr.

3.2. Radiolabelling with Bifunctional Chelators

DFO is a cyclic hexadentate chelator that is widely used to chelate 89Zr. Compared to DTPA, DFO shows a greater stability in vivo, without affecting the in vivo biodistribution of the NPs, and allowing a radiolabelling process to be performed at mild temperatures and with a neutral pH [24][25][26].
The radiolabelling via the 89Zr-DFO coupling method usually provides a first step, whereby the NPs are conjugated to DFO, and this is followed by the addition of the isotope.
The DFO can also be used to stably label the isotope in the core of the NPs. For example, Li et al. radiolabelled liposomal NPs with the ligand-exchange method. The authors labelled the 8-HQ (oxine) to the isotope, thereby allowing the delivering of 89Zr into the liposomal cavity where it was previously encapsulated in the DFO. Briefly, the authors added the DFO into the NPs solution, and this was followed by 30 min of incubation at 35 °C and 5 min of sonication, thereby allowing the encapsulation of DFO into the liposomal cavity. Then, the radioisotope was chelated with 8-HQ (oxine). The final mixture was kept at room temperature for 30 min before the addition of the DFO-liposome solution, which was followed by another 60 min of incubation. The volume ratio of the final solution of 89Zr:8-HQ:DFO-liposome was 2:1:3. The RCY was 98%, but after its storage for 48 h at 4 °C, this was reduced to 83% [27].
Ferumoxytol (superparamagnetic iron oxide NPs that are coated with polyglucose sorbitol carboxymethylether) was labelled with 89Zr-DFO, which was used as a PET/MRI contrast agent. For the success of the radiolabelling process, a modification of the surface chemistry of the drug was needed and, in particular, an amination of the particles to bind the DFO to Ferumoxytol was carried out.
After the radiolabelling process, which consisted of adding 89Zr in the modified ferumoxytol and mixing them at 37 °C for 1 h, they analyzed the LE before its purification (>90%) and the radiochemical purity (99%, and this remained stable for over 24 h at 37 °C in mouse serum) [28].
High-density lipoprotein (HDL) has been radiolabelled with a high efficiency in several studies, and it is usually applied to image tumor-associated macrophages (TAMs) or activated macrophages in atherosclerosis. The 89Zr physical half-life matches the biologic half-life of HDL, thus making 89Zr-HDL a perfect radiopharmaceutical. For these studies, the labelling process required a previous modification of HDL with a DFO. The conjugation was obtained via a reaction between the DFO and the lysine amino group of ApoA-1. This method showed a high radiochemical purity [29][30][31][32][33][34][35].
Dextran nanoparticles were studied as a nuclear probe for the detection of inflammatory leukocytes in atherosclerotic plaque. Before the radiolabelling was performed, the NPs were modified with epichlorohydrin through a cross-link reaction, and then, they were aminated with an ethylene diamine, thereby obtaining amino-dextran NPs (DNP-NH2). Finally, they were conjugated with p-isothiocyanatobenzyl desferoxamine (SCN-Bz-Df) and radiolabelled with 89Zr, and then, they were added to the final mixture at room temperature [36].
AuNPs were radiolabelled with 89Zr and conjugated with a monoclonal antibody (cetuximab) for to test their quantitative imaging performance in a PET application. The monoclonal antibody was first radiolabelled with 89Zr via desferal moiety, and then, it was conjugated with AuNPs using carbodiimide chemistry. The radiochemical purity after the purification was >95%. The immuno-PET showed a higher tumor-to-background ratio of 89Zr-cetuximab-AuNPs than 89Zr-cetuximab did alone, without there being significant differences in the biodistribution, thereby proving that it is a promising tool for a future theragnostic approach. In another study that was conducted by the same group, AuNPs were conjugated with the anti-CD105 antibody which had been previously radiolabelled with 89Zr using the same strategy. These NPs were used to perform a quantitative PET imaging of mice bearing tumors. The results confirmed its high specificity in vivo [37][38].

4. Radiolabelling with Iodine-124

Among the positron-emitting radionuclides, iodine-124 (124I) has the longest half-life (T1/2 = 4.2 days). This characteristic, when it is combined with its chemical properties, contribute to its wide diffusion in the study of NPs pharmacokinetic [39].
There are few data that are available in the literature regarding direct labelling, such as the remote loading method or the use of Iodo-beads and Iodogen, or via Chloramine-T oxidation. On the contrary, for indirect labelling, various techniques have been proposed, including the use of Bolton–Hunter reagent as BFC. Some of these techniques reach the best performing at high temperatures, which can be a limit of them.

4.1. Direct Radiolabelling

For the iodine radiolabelling of liposomal NPs, the direct labelling method demonstrated to have a higher efficiency than the indirect method using the Bolton–Hunter reagent did [40][41]. For this reason, a direct method to encapsulate 124I in the liposomal NPs has been used. Here, isotopes are conjugated with compounds that allow the passive crossing of them through the membrane of the NPs. The most frequently used compound for the remote loading of 124I in the liposomal NPs is the amino diatrizoic acid (ADA), a iodinated contrast agent that is usually applied in Computed Tomography (CT). The compound is first conjugated to the isotope, and then, thanks to solutions that are based on citrate or ammonium sulphate that create a transmembrane pH gradient, the compound is able to cross the lipid membrane. The non-protonated compound, once it is inside the liposomal NPs, is protonated and cannot be released from the inner core [42].
A novel class of NPs, which are defined as “upconversion NPs (UCNPs)”, are composed by fluorescent metal-based materials such as NaYF4, NaGdF4, NaLaF4, LaF3, GdF3, CeO2, LiNaF4, etc. They are characterized by an emission in the near-infrared (NIR) spectrum, thus resulting in a high degree of the penetration of the light through the biological tissues [43][44]. Lee et al. combined the optical properties of Er3+/Yb3+ which was co-doped NaGdF4 NPs using PET/MRI property imaging, thereby developing a multimodal tool for tumor angiogenesis imaging. The UCNPs were radiolabelled with 124I using Iodo-Beads. The NPs that were functionalized with the arginine-glycine-aspartic acid (RGD) motifs had a surface-exposed tyrosine residue that allowed the direct conjugation of them with 124I using the polystyrene beads. The resulting radiolabelling yield was approximately 19%, and the in vivo tumor uptake of 124I-c(RGDyk)2-UCNPs was ∼2%ID/g at 4 h, thus confirming that there was radiolabelling instability due to the de-iodination of radioiodine from the NPs. Further studies are needed to improve the stability of radiolabelling [45].
The same method was applied for polymeric NPs that were synthetized by poly(4-vinylphenol) (PVPh) polymers. The large number of phenolic groups on their polymeric backbone allowed an easy radio-iodination to occur, thus resulting in a high radiolabelling yield (~90%). The PVPh-NPs were incubated with iodination beads (Iodo-beads) including the 124I isotope. When the beads were removed, the reaction was stopped. The NPs were then conjugated with three different mAbs: anti-adhesion molecule of platelet-1 endothelial cells (PECAM-1), anti-thrombomodulin (TM), and anti-PV1. The results showed that the NPs targeting PECAM-1 enabled a high-quality PET image to be obtained of the pulmonary vascularity in the murine models [46]. A similar approach was used with Iodination vials (Iodogen), where the iodine nuclides are blocked in the reaction vials. The isotope covalently labels the tyrosine motifs on the NPs’ surface [47].
By contrast, the Chloramine-T method has been used to radiolabel Gold NPs. Iodination was performed by adding the Chloramine-T reagent to the solution containing the isotope and the NPs. The free isotope was then removed by ultracentrifugation. The 124I-AuNPs were used for in vivo tumor imaging through a micro-PET in a breast cancer mice model and to track the trafficking of the dendritic cells to evaluate the efficacy of the DC-based immunotherapy [48][49].
It has been reported that iodine isotopes have a high affinity for gold nanomaterials, thus resulting in them having a direct and strong bond with them [50]. 124I-labeled gold nanostar probes (124I-GNS) that are used for brain tumor imaging are selectively brain-tumor-targeting thanks to the EPR effect, thus making the 124I-GNS nanoprobe promising for its future clinical applications to diagnose brain tumors [51].

4.2. Radiolabelling with Bifunctional Chelators

The Bolton–Hunter method has been successfully used to radiolabel silica NPs with 124I. The NPs with an average diameter of 20–25 nm and surface-free amino groups were efficiently conjugated with a covalent linkage to the NHS ester group that had been previously radiolabelled with 124I (124I-NHS) for the PET imaging to be performed in vivo [52].

5. Radiolabelling with Fluorine-18

Fluorine-18 that is labelled with a deoxyglucose molecule ([18F]-FDG) is the main radiopharmaceutical that is used in clinical PET imaging. The main drawback of this radionuclide is its short half-life (T1/2 = 109.7 min), which restricts its use to studies of small molecules with a fast biodistribution. The NPs generally have a longer pharmacokinetic that does not match with the half-life of this isotope, thus limiting its use in nanomedicine.

5.1. Direct Radiolabelling

One strategy for directly radiolabelling the NPs with 18F is based on bombarding the nanomaterials with a neutron or proton, whereby an atom of the NP undergoes a nuclear reaction, thereby providing a radionuclide in situ. This strategy was applied for the radiolabelling of 18O-enriched tin oxide (Al2O3) NPs by their direct irradiation with 16 MeV protons. The nuclear reaction allowed the transmutation of 18O in 18F. This method provided the precise control of the isotope position, thus achieving a high radiochemical stability. However, its application is limited to inorganic nanomaterials since the organic NPs can be affected and modified in their structure by the nuclear reaction. Furthermore, this method requires specific instrumentation with a high management costs [53]. Unlike the metal radionuclides that prefer to undergo labelling via chelators, the halogen radionuclides, such as 18F, are usually labelled directly with a chemical group (chemical adsorption) or with a prosthetic group (indirect labelling) on the surface of the NPs. Chemical adsorption usually occurs with the reaction between the soft acids and the soft bases or between the hard acids and the hard bases, thereby creating strong coordination bonds between the isotope and chemical groups on nanomaterials. Several studies have been reported in the literature, showed the strong affinity between 18F and the rare earth NPs, such as KGdF4, NaYF4:Yb, Gd-NaYF4:Yb, NaYF4:Yb, and NaYF4:GdYb. The chemical adsorption of fluorine on the NPs’ surface is a simple and fast method, whereby only the incubation of the isotope with the NP leads to a chemical stability of the compound with a RCY that is higher than 90% and a high radiochemical stability in vivo. The main limitation of this approach is the high temperatures that are required to achieve the conjugation [54][55][56].
Rare-earth fluoride NPs, such as yttrium trifluoride (YF3) nanoparticles could be radiolabelled by mixing [18F] the potassium fluoride solution with an aqueous solutions of NPs at room temperature, which would be followed by a 5 to 10 min incubation procedure. The free 18F can then be removed by centrifugation. Excellent radiolabelling yields were reported, which were in the range of 80–95% [57]. This strategy could be also used with magnetic nanoparticles, such as MnFe2O4 and Fe3O4, where the radiolabelling process consists of adding a [18F] sodium fluoride solution in a solution of NPs and incubating them while they are continuously shaken at room temperature for 10 min [58]. Indeed, UCNPs that are composed of lanthanide nanocrystals (Gd3+/Yb3+/Er3+) with co-doped NaYF4 were efficiently and directly radiolabelled with 18F through a simple incubation. The strong binding between Y3+ and F allowed for a high LE. In vivo, the low bone uptake demonstrated the stability of this radiopharmaceutical.
The advantage of lanthanide materials is that they are characterized by their luminescent and magnetic properties, which provide a high spatial resolution and a high sensitivity when they are used in MRIs and fluorescent imaging, while the positron-emitting radionuclide provides functional information in PET imaging. Indeed, with a single nano-radiopharmaceutical, it is possible to obtain multimodal imaging at the molecular level with high sensitivity [59].

5.2. Radiolabelling with Bifunctional Chelators

For the indirect surface labelling of 18F with prosthetic groups, it is typical that the copper-catalyzed azide–alkyne cycloaddition click chemistry is applied [60]. With this method, the prosthetic groups of the but-3-yn-1-amine modified USPIONPs, maleimide-AuNPs, and aminated IONPs were efficiently conjugated with 18F under mild conditions and with high yields [61][62][63].
Nanodiamonds (DNPs) are sp3-carbon NPs, which are a promising biomaterial due to their good biocompatibility, possibility to be functionalized for drug delivery and ability to cross the cell membrane. The radiolabelling of these NPs was made possible by covalently attaching the ω-aminopropyl groups to the surface of the DNP, a reaction that occurs under mild conditions with high yields and is a well-established methodology for functionalizing various solid materials, including silicas and metal oxides. The resulting amino-DNPs were treated with 18F-SFB (N-Succinimidyl 4-[18F] Fluorobenzoate), thereby obtaining 18F-radiolabelled NPs. In the biodistribution studies, it was observed that these NPs accumulate in the lung, spleen, and liver and are excreted into the urinary tract [64].

References

  1. Capriotti, G.; Varani, M.; Lauri, C.; Franchi, G.; Pizzichini, P.; Signore, A. Copper-64 labeled nanoparticles for positron emission tomography imaging: A review of the recent literature. Q. J. Nucl. Med. Mol. Imaging 2020, 64, 346–355.
  2. Shi, S.; Xu, C.; Yang, K.; Goel, S.; Valdovinos, H.F.; Luo, H.; Ehlerding, E.B.; England, C.G.; Cheng, L.; Chen, F.; et al. Chelator-Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation. Angew. Chem. Int. Ed. Engl. 2017, 56, 2889–2892.
  3. Shaffer, T.M.; Wall, M.A.; Harmsen, S.; Longo, V.A.; Drain, C.M.; Kircher, M.F.; Grimm, J. Silica nanoparticles as substrates for chelator-free labeling of oxophilic radioisotopes. Nano Lett. 2015, 15, 864–868.
  4. Shaffer, T.M.; Harmsen, S.; Khwaja, E.; Kircher, M.F.; Drain, C.M.; Grimm, J. Stable Radiolabeling of Sulfur-Functionalized Silica Nanoparticles with Copper-64. Nano Lett. 2016, 16, 5601–5604.
  5. Cisneros, B.T.; Law, J.J.; Matson, M.L.; Azhdarinia, A.; Sevick-Muraca, E.M.; Wilson, L.J. Stable confinement of positron emission tomography and magnetic resonance agents within carbon nanotubes for bimodal imaging. Nanomedicine (Lond) 2014, 16, 2499–2509.
  6. Pressly, E.D.; Rossin, R.; Hagooly, A.; Fukukawa, K.; Messmore, B.W.; Welch, M.J.; Wooley, K.L.; Lamm, M.S.; Hule, R.A.; Pochan, D.J.; et al. Structural effects on the biodistribution and positron emission tomography (PET) imaging of well-defined (64)Cu-labeled nanoparticles comprised of amphiphilic block graft copolymers. Biomacromolecules 2007, 8, 3126–3134.
  7. Velikyan, I. Positron emitting Ga-based imaging agents: Chemistry and diversity. Med. Chem. 2011, 7, 345–379.
  8. Locatelli, E.; Gil, L.; Israel, L.L.; Passoni, L.; Naddaka, M.; Pucci, A.; Reese, T.; Gomez-Vallejo, V.; Milani, P.; Matteoli, M.; et al. Biocompatible nanocomposite for PET/MRI hybrid imaging. Int. J. Nanomed. 2012, 7, 6021–6033.
  9. Tang, T.; Wei, Y.; Yang, Q.; Yang, Y.; Sailor, M.J.; Pang, H.B. Rapid chelator-free radiolabeling of quantum dots for in vivo imaging. Nanoscale 2019, 11, 22248–22254.
  10. Karageorgou, M.A.; Vranješ-Djurić, S.; Radović, M.; Lyberopoulou, A.; Antić, B.; Rouchota, M.; Gazouli, M.; Loudos, G.; Xanthopoulos, S.; Sideratou, Z.; et al. Gallium-68 Labeled Iron Oxide Nanoparticles Coated with 2,3-Dicarboxypropane-1,1-diphosphonic Acid as a Potential PET/MR Imaging Agent: A Proof-of-Concept Study. Contrast Media Mol. Imaging 2017, 2017, 6951240.
  11. Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; Laberge, L.; Rousell, J. The use of microwave ovens for rapid organic synthesis. Tetrahedron. Lett. 1986, 27, 279–282.
  12. Pellico, J.; Ruiz-Cabello, J.; Saiz-Alía, M.; Del Rosario, G.; Caja, S.; Montoya, M.; Fernández de Manuel, L.; Morales, M.P.; Gutiérrez, L.; Galiana, B.; et al. Fast synthesis and bioconjugation of (68) Ga core-doped extremely small iron oxide nanoparticles for PET/MR imaging. Contrast Media Mol. Imaging 2016, 11, 203–210.
  13. Chen, L.; Ge, J.; Huang, B.; Zhou, D.; Huang, G.; Zeng, J.; Gao, M. Anchoring Group Mediated Radiolabeling for Achieving Robust Nanoimaging Probes. Small 2021, 17, 2104977.
  14. Ge, J.; Chen, L.; Huang, B.; Gao, Y.; Zhou, D.; Zhou, Y.; Chen, C.; Wen, L.; Li, Q.; Zeng, J.; et al. Anchoring Group-Mediated Radiolabeling of Inorganic Nanoparticles─A Universal Method for Constructing Nuclear Medicine Imaging Nanoprobes. ACS Appl. Mater. Interfaces 2022, 14, 8838–8846.
  15. Hong, H.; Zhang, Y.; Engle, J.W.; Nayak, T.R.; Theuer, C.P.; Nickles, R.J.; Barnhart, T.E.; Cai, W. In vivo targeting and positron emission tomography imaging of tumor vasculature with (66)Ga-labeled nano-graphene. Biomaterials 2012, 33, 4147–4156.
  16. Kang, W.J.; Lee, J.; Lee, Y.S.; Cho, S.; Ali, B.A.; Al-Khedhairy, A.A.; Heo, H.; Kim, S. Multimodal imaging probe for targeting cancer cells using uMUC-1 aptamer. Colloids Surf. B Biointerfaces 2015, 136, 134–140.
  17. Kim, S.M.; Chae, M.K.; Yim, M.S.; Jeong, I.H.; Cho, J.; Lee, C.; Ryu, E.K. Hybrid PET/MR imaging of tumors using an oleanolic acid-conjugated nanoparticle. Biomaterials 2013, 34, 8114–8121.
  18. Ghai, A.; Singh, B.; Panwar Hazari, P.; Schultz, M.K.; Parmar, A.; Kumar, P.; Sharma, S.; Dhawan, D.; Kumar Mishra, A. Radiolabeling optimization and characterization of (68)Ga labeled DOTA-polyamido-amine dendrimer conjugate—Animal biodistribution and PET imaging results. Appl. Radiat. Isot. 2015, 105, 40–46.
  19. Hajiramezanali, M.; Atyabi, F.; Mosayebnia, M.; Akhlaghi, M.; Geramifar, P.; Jalilian, A.R.; Mazidi, S.M.; Yousefnia, H.; Shahhosseini, S.; Beiki, D. 68Ga-radiolabeled bombesin-conjugated to trimethyl chitosan-coated superparamagnetic nanoparticles for molecular imaging: Preparation, characterization and biological evaluation. Int. J. Nanomed. 2019, 14, 2591–2605.
  20. Polyak, A.; Naszalyi Nagy, L.; Mihaly, J.; Görres, S.; Wittneben, A.; Leiter, I.; Bankstahl, J.P.; Sajti, L.; Kellermayer, M.; Zrínyi, M.; et al. Preparation and 68Ga-radiolabeling of porous zirconia nanoparticle platform for PET/CT-imaging guided drug delivery. J. Pharm. Biomed. Anal. 2017, 137, 146–150.
  21. Bouziotis, P.; Stellas, D.; Thomas, E.; Truillet, C.; Tsoukalas, C.; Lux, F.; Tsotakos, T.; Xanthopoulos, S.; Paravatou-Petsotas, M.; Gaitanis, A.; et al. 68Ga-radiolabeled AGuIX nanoparticles as dual-modality imaging agents for PET/MRI-guided radiation therapy. Nanomedicine 2017, 12, 1561–1574.
  22. Lahooti, A.; Shanehsazzadeh, S.; Laurent, S. Preliminary studies of 68Ga-NODA-USPION-BBN as a dual-modality contrast agent for use in positron emission tomography/magnetic resonance imaging. Nanotechnology 2020, 31, 015102.
  23. Körhegyi, Z.; Rózsa, D.; Hajdu, I.; Bodnár, M.; Kertész, I.; Kerekes, K.; Kun, S.; Kollár, J.; Varga, J.; Garai, I.; et al. Synthesis of 68Ga-Labeled Biopolymer-based Nanoparticle Imaging Agents for Positron-emission Tomography. Anticancer. Res. 2019, 39, 2415–2427.
  24. Price, E.W.; Orvig, C. Matching Chelators to Radiometals for Radiopharmaceuticals. Chem. Soc. Rev. 2014, 43, 260–290.
  25. Pérez-Medina, C.; Abdel-Atti, D.; Zhang, Y.; Longo, V.A.; Irwin, C.P.; Binderup, T.; Ruiz-Cabello, J.; Fayad, Z.A.; Lewis, J.S.; Mulder, W.J.; et al. A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting. J. Nucl. Med. 2014, 55, 1706–1711.
  26. Senders, M.L.; Meerwaldt, A.E.; van Leent, M.M.T.; Sanchez-Gaytan, B.L.; van de Voort, J.C.; Toner, Y.C.; Maier, A.; Klein, E.D.; Sullivan, N.A.T.; Sofias, A.M.; et al. Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging. Nat. Nanotechnol. 2020, 15, 398–405.
  27. Li, N.; Yu, Z.; Pham, T.T.; Blower, P.J.; Yan, R. A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography. Int. J. Nanomed. 2017, 12, 3281–3294.
  28. Thorek, D.L.; Ulmert, D.; Diop, N.F.; Lupu, M.E.; Doran, M.G.; Huang, R.; Abou, D.S.; Larson, S.M.; Grimm, J. Non-invasive mapping of deep-tissue lymph nodes in live animals using a multimodal PET/MRI nanoparticle. Nat. Commun. 2014, 5, 3097.
  29. Pérez-Medina, C.; Tang, J.; Abdel-Atti, D.; Hogstad, B.; Merad, M.; Fisher, E.A.; Fayad, Z.A.; Lewis, J.S.; Mulder, W.J.; Reiner, T. PET Imaging of Tumor-Associated Macrophages with 89Zr-Labeled High-Density Lipoprotein Nanoparticles. J. Nucl. Med. 2015, 56, 1272–1277.
  30. Tang, J.; Baxter, S.; Menon, A.; Alaarg, A.; Sanchez-Gaytan, B.L.; Fay, F.; Zhao, Y.; Ouimet, M.; Braza, M.S.; Longo, V.A.; et al. Immune cell screening of a nanoparticle library improves atherosclerosis therapy. Proc. Natl. Acad. Sci. USA 2016, 113, E6731–E6740.
  31. Zheng, K.H.; van der Valk, F.M.; Smits, L.P.; Sandberg, M.; Dasseux, J.L.; Baron, R.; Barbaras, R.; Keyserling, C.; Coolen, B.F.; Nederveen, A.J.; et al. HDL mimetic CER-001 targets atherosclerotic plaques in patients. Atherosclerosis 2016, 51, 381–388.
  32. Binderup, T.; Duivenvoorden, R.; Fay, F.; van Leent, M.M.T.; Malkus, J.; Baxter, S.; Ishino, S.; Zhao, Y.; Sanchez-Gaytan, B.; Teunissen, A.J.P.; et al. Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species. Sci. Transl. Med. 2019, 11, 7736.
  33. Chen, J.; Zhang, X.; Millican, R.; Creutzmann, J.E.; Martin, S.; Jun, H.W. High density lipoprotein mimicking nanoparticles for atherosclerosis. Nano Converg. 2020, 7, 6.
  34. Mason, C.A.; Kossatz, S.; Carter, L.M.; Pirovano, G.; Brand, C.; Guru, N.; Pérez-Medina, C.; Lewis, J.S.; Mulder, W.J.M.; Reiner, T. An 89Zr-HDL PET Tracer Monitors Response to a CSF1R Inhibitor. J. Nucl. Med. 2020, 61, 433–436.
  35. Lobatto, M.E.; Binderup, T.; Robson, P.M.; Giesen, L.F.P.; Calcagno, C.; Witjes, J.; Fay, F.; Baxter, S.; Wessel, C.H.; Eldib, M.; et al. Multimodal Positron Emission Tomography Imaging to Quantify Uptake of 89Zr-Labeled Liposomes in the Atherosclerotic Vessel Wall. Bioconjug. Chem. 2020, 31, 360–368.
  36. Majmudar, M.D.; Yoo, J.; Keliher, E.J.; Truelove, J.J.; Iwamoto, Y.; Sena, B.; Dutta, P.; Borodovsky, A.; Fitzgerald, K.; Di Carli, M.F.; et al. Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques. Circ. Res. 2013, 112, 755–761.
  37. Karmani, L.; Labar, D.; Valembois, V.; Bouchat, V.; Nagaswaran, P.G.; Bol, A.; Gillart, J.; Levêque, P.; Bouzin, C.; Bonifazi, D.; et al. Antibody-functionalized nanoparticles for imaging cancer: Influence of conjugation to gold nanoparticles on the biodistribution of 89Zr-labeled cetuximab in mice. Contrast Media Mol. Imaging 2013, 8, 402–408.
  38. Karmani, L.; Bouchat, V.; Bouzin, C.; Levêque, P.; Labar, D.; Bol, A.; Deumer, G.; Marega, R.; Bonifazi, D.; Haufroid, V.; et al. (89)Zr-labeled anti-endoglin antibody-targeted gold nanoparticles for imaging cancer: Implications for future cancer therapy. Nanomedicine 2014, 9, 1923–1937.
  39. Chacko, A.M.; Divgi, C.R. Radiopharmaceutical chemistry with iodine-124: A non-standard radiohalogen for positron emission tomography. Med. Chem. 2011, 7, 395–412.
  40. Mougin-Degraef, M.; Jestin, E.; Bruel, D.; Remaud-Le Saëc, P.; Morandeau, L.; Faivre-Chauvet, A.; Barbet, J. High-activity radio-iodine labeling of conventional and stealth liposomes. J. Liposome Res. 2006, 16, 91–102.
  41. Leike, J.U.; Sachse, A.; Rupp, K. Characterization of Continuously Extruded Iopromide-Carrying Liposomes for Computed Tomography Blood-Pool Imaging. Investig. Radiol. 2001, 36, 303–308.
  42. Engudar, G.; Schaarup-Jensen, H.; Fliedner, F.P.; Hansen, A.E.; Kempen, P.; Jølck, R.I.; Kjæer, A.; Andresen, T.L.; Clausen, M.H.; Jensen, A.I.; et al. Remote loading of liposomes with a 124I-radioiodinated compound and their in vivo evaluation by PET/CT in a murine tumor model. Theranostics 2018, 8, 5828–5841.
  43. Cho, J.H.; Bass, M.; Babu, S.; Dowding, J.M.; Self, W.T.; Seal, S. Up conversion luminescence of Yb3+ -Er3+ codoped CeO2 nanocrystals with imaging applications. J. Lumin. 2012, 132, 743–749.
  44. Liang, G.; Wang, H.; Shi, H.; Wang, H.; Zhu, M.; Jing, A.; Li, J.; Li, G. Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment. J. Nanobiotechnol. 2020, 18, 154.
  45. Lee, J.; Lee, T.S.; Ryu, J.; Hong, S.; Kang, M.; Im, K.; Kang, J.H.; Lim, S.M.; Park, S.; Song, R. RGD peptide-conjugated multimodal NaGdF4:Yb3+/Er3+ nanophosphors for upconversion luminescence, MR, and PET imaging of tumor angiogenesis. J. Nucl. Med. 2013, 54, 96–103.
  46. Simone, E.A.; Zern, B.J.; Chacko, A.M.; Mikitsh, J.L.; Blankemeyer, E.R.; Muro, S.; Stan, R.V.; Muzykantov, V.R. Endothelial targeting of polymeric nanoparticles stably labeled with the PET imaging radioisotope iodine-124. Biomaterials 2012, 33, 5406–5413.
  47. Royo, F.; Cossío, U.; Ruiz de Angulo, A.; Llop, J.; Falcon-Perez, J.M. Modification of the glycosylation of extracellular vesicles alters their biodistribution in mice. Nanoscale 2019, 11, 1531–1537.
  48. Lee, S.B.; Lee, S.W.; Jeong, S.Y.; Yoon, G.; Cho, S.J.; Kim, S.K.; Lee, I.K.; Ahn, B.C.; Lee, J.; Jeon, Y.H. Engineering of Radioiodine-Labeled Gold Core-Shell Nanoparticles As Efficient Nuclear Medicine Imaging Agents for Trafficking of Dendritic Cells. ACS Appl. Mater. Interfaces 2017, 9, 8480–8489.
  49. Lee, S.B.; Kumar, D.; Li, Y.; Lee, I.K.; Cho, S.J.; Kim, S.K.; Lee, S.W.; Jeong, S.Y.; Lee, J.; Jeon, Y.H. PEGylated crushed gold shell-radiolabeled core nanoballs for in vivo tumor imaging with dual positron emission tomography and Cerenkov luminescent imaging. J. Nanobiotechnol. 2018, 16, 41.
  50. Smith, D.K.; Miller, N.R.; Korgel, B.A. Iodide in CTAB prevents gold nanorod formation. Langmuir 2009, 25, 9518–9524.
  51. Liu, Y.; Carpenter, A.B.; Pirozzi, C.J.; Yuan, H.; Waitkus, M.S.; Zhou, Z.; Hansen, L.; Seywald, M.; Odion, R.; Greer, P.K.; et al. Non-invasive sensitive brain tumor detection using dual-modality bioimaging nanoprobe. Nanotechnology 2019, 30, 275101.
  52. Kumar, R.; Roy, I.; Ohulchanskky, T.Y.; Vathy, L.A.; Bergey, E.J.; Sajjad, M.; Prasad, P.N. In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles. ACS Nano 2010, 4, 699–708.
  53. Pérez-Campaña, C.; Gómez-Vallejo, V.; Puigivila, M.; Martín, A.; Calvo-Fernández, T.; Moya, S.E.; Ziolo, R.F.; Reese, T.; Llop, J. Biodistribution of different sized nanoparticles assessed by positron emission tomography: A general strategy for direct activation of metal oxide particles. ACS Nano 2013, 7, 3498–3505.
  54. Liu, Q.; Sun, Y.; Li, C.; Zhou, J.; Li, C.; Yang, T.; Zhang, X.; Yi, T.; Wu, D.; Li, F. 18F-Labeled magnetic-upconversion nanophosphors via rare-Earth cation-assisted ligand assembly. ACS Nano 2011, 5, 3146–3157.
  55. Sun, Y.; Yu, M.; Liang, S.; Zhang, Y.; Li, C.; Mou, T.; Yang, W.; Zhang, X.; Li, B.; Huang, C.; et al. Fluorine-18 labeled rare-earth nanoparticles for positron emission tomography (PET) imaging of sentinel lymph node. Biomaterials 2011, 32, 2999–3007.
  56. Cao, X.; Cao, F.; Xiong, L.; Yang, Y.; Cao, T.; Cai, X.; Hai, W.; Li, B.; Guo, Y.; Zhang, Y.; et al. Cytotoxicity, tumor targeting and PET imaging of sub-5 nm KGdF4 multifunctional rare earth nanoparticles. Nanoscale 2015, 7, 13404–13409.
  57. Xiong, L.; Shen, B.; Behera, D.; Gambhir, S.S.; Chin, F.T.; Rao, J. Synthesis of ligand-functionalized water-soluble YF3 nanoparticles for PET imaging. Nanoscale 2013, 5, 3253–3256.
  58. Cui, X.; Belo, S.; Krüger, D.; Yan, Y.; de Rosales, R.T.; Jauregui-Osoro, M.; Ye, H.; Su, S.; Mathe, D.; Kovács, N.; et al. Aluminium hydroxide stabilised MnFe2O4 and Fe3O4 nanoparticles as dual-modality contrasts agent for MRI and PET imaging. Biomaterials 2014, 35, 5840–5846.
  59. Zhou, J.; Yu, M.; Sun, Y.; Zhang, X.; Zhu, X.; Wu, Z.; Wu, D.; Li, F. Fluorine-18-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors for multimodality PET/MR/UCL imaging. Biomaterials 2011, 32, 1148–1156.
  60. Wang, Q.; Chan, T.R.; Hilgraf, R.; Fokin, V.V.; Sharpless, K.B.; Finn, M.G. Bioconjugation by copper(I)-catalyzed azide-alkyne cycloaddition. J. Am. Chem. Soc. 2003, 125, 3192–3193.
  61. Nahrendorf, M.; Keliher, E.; Marinelli, B.; Waterman, P.; Feruglio, P.F.; Fexon, L.; Pivovarov, M.; Swirski, F.K.; Pittet, M.J.; Vinegoni, C.; et al. Hybrid PET-optical imaging using targeted probes. Proc. Natl. Acad. Sci. USA 2010, 107, 7910–7915.
  62. Zhu, J.; Chin, J.; Wängler, C.; Wängler, B.; Lennox, R.B.; Schirrmacher, R. Rapid (18)F-labeling and loading of PEGylated gold nanoparticles for in vivo applications. Bioconjug. Chem. 2014, 25, 1143–1150.
  63. Tong, M.K.; Liu, Z.T.; Cai, J.L.; Liu, S.Y.; Zhang, C.F. Development of dual modality (PET/MRI) and dual targeting (αVβ3/EGFR) magnetic nanoprobe for early detection of lung cancer. Nanomed. Nanotechnol. 2016, 12, 495–496.
  64. Rojas, S.; Gispert, J.D.; Martín, R.; Abad, S.; Menchón, C.; Pareto, D.; Víctor, V.M.; Alvaro, M.; García, H.; Herance, J.R. Biodistribution of amino-functionalized diamond nanoparticles. In vivo studies based on 18F radionuclide emission. ACS Nano 2011, 5, 5552–5559.
More
Information
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , , ,
View Times: 436
Entry Collection: Biopharmaceuticals Technology
Revisions: 4 times (View History)
Update Date: 21 Nov 2022
1000/1000
Video Production Service