Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET

Normandin, Marc D.; Yuan, Haidong; Wilks, Moses Q.; Chen, Howard H.; Kinsella, Joseph M.; Cho, Hoonsung; Guehl, Nicolas J.; Absi-Halabi, Nader; Hosseini, Seyed Ali; Fakhri, Georges El; Sosnovik, David E.; Josephson, Lee

doi:10.1002/anie.201505525

Cited by 30 publications

(43 citation statements)

References 24 publications

(16 reference statements)

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“…2a), and Cy5.5-FH (Fig. 2b)), have the same physical properties (size, relaxivity) and the same blood half-life 19 .…”

Section: Introductionmentioning

confidence: 95%

“…In addition, we present a strategy for labeling FH NPs with fluorescent Cy5.5 fluorophores, which enables researchers to examine NP-internalizing cells by flow cytometry 19 .…”

Section: Introductionmentioning

confidence: 99%

“…18). A typical HIR reaction requires a milligram of NP iron and several millicuries of radiometal, a situation that corresponds to a molar ratio of iron to radiocation of at least 100 for all radiocations employed here 19 . Hence, the over-all chemical composition of FH NPs is not substantially altered by radiocation addition.…”

Section: Introductionmentioning

confidence: 99%

“…2a) 18,19 . In the first stage, the FH NP is ‘loaded’ with a radiocation ( 111 In 3 + , 89 Zr 4 + , or 64 Cu 2 + ) by heating (120 °C, 2 h, Steps 6–8).…”

Section: Introductionmentioning

confidence: 99%

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Heat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry

et al. 2018

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Feraheme (FH) nanoparticles (NPs) have been used extensively for treatment of iron anemia (due to their slow release of ionic iron in acidic environments). In addition, injected FH NPs are internalized by monocytes and function as MRI biomarkers for the pathological accumulation of monocytes in disease. We have recently expanded these applications by radiolabeling FH NPs for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) imaging using a heat-induced radiolabeling (HIR) strategy. Imaging FH NPs using PET/SPECT has important advantages over MRI due to lower iron doses and improved quantitation of tissue NP concentrations. HIR of FH NPs leaves the physical and biological properties of the NPs unchanged and allows researchers to build on the extensive knowledge obtained about the pharmacokinetic and safety aspects of FH NPs. In this protocol, we present the step-by-step procedures for heat (120 °C)-induced bonding of three widely employed radiocations (89Zr4 + or 64Cu2 + for PET, and 111In3 + for SPECT) to FH NPs using a chelateless radiocation surface adsorption (RSA) approach. In addition, we describe the conversion of FH carboxyl groups into amines and their reaction with an N-hydroxysuccinimide (NHS) of a Cy5.5 fluorophore. This yields Cy5.5-FH, a fluorescent FH that enables the cells internalizing Cy5.5-FH to be examined using flow cytometry. Finally, we describe procedures for in vivo and ex vivo uptake of Cy5.5-FH by monocytes and for in vivo microPET/CT imaging of HIR-FH NPs. Synthesis of HIR-FH requires experience with working with radioactive cations and can be completed within < 4 h. Synthesis of Cy5.5-FH NPs takes ~17 h.

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“…2a), and Cy5.5-FH (Fig. 2b)), have the same physical properties (size, relaxivity) and the same blood half-life 19 .…”

Section: Introductionmentioning

confidence: 95%

“…In addition, we present a strategy for labeling FH NPs with fluorescent Cy5.5 fluorophores, which enables researchers to examine NP-internalizing cells by flow cytometry 19 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…2a) 18,19 . In the first stage, the FH NP is ‘loaded’ with a radiocation ( 111 In 3 + , 89 Zr 4 + , or 64 Cu 2 + ) by heating (120 °C, 2 h, Steps 6–8).…”

Section: Introductionmentioning

confidence: 99%

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Heat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry

et al. 2018

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“…The same approach has been used to monitor monocyte recruitment in live atherosclerotic apolipoprotein E knockout (Apoe -/-) mice for up to 7 days with Indium-111 ( 111 In)-tagged monocytes and micro-SPECT/CT [180]. Moreover, the use of Zirconium-89 ( 89 Zr)-feraheme nanoparticles, which are specifically taken up by blood monocytes, can enable studying monocyte dynamics by PET [190].…”

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confidence: 99%

Targeted therapeutics in inflammatory atherosclerosis

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Anchoring Group Mediated Radiolabeling for Achieving Robust Nanoimaging Probes

Chen

Huang

et al. 2021

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Radiolabeling counts for much in the functionalization of inorganic nanoparticles (NPs) because it endows NPs with high‐sensitive imaging capacities apart from providing accurate pharmacokinetic information on the labeled particles, which makes the development of relevant radiolabeling chemistry highly desirable. Herein, a novel Ligand Anchoring Group MEdiated RAdioLabeling (LAGMERAL) method is reported, in which a polyethylene glycol (PEG) ligand with a diphosphonate (DP) terminal group plays a key role. It offers possibilities to radiolabel NPs through the spare coordination sites of the DP anchoring group. Through X‐ray absorption spectroscopy studies, the coordination states of the foreign metal ions on the particle surface are investigated. In addition, radioactive Fe3O4 NPs are prepared by colabeling the particles with 125I at the outskirt of the particles through a phenolic hydroxyl moiety of the PEG ligand, and 99mTc at the root of the ligand, respectively. In this way, the stabilities of these types of radiolabeling are compared both in vitro and in vivo to show the advantages of the LAGMERAL method. The outstanding stability of probe and simplicity of the labeling process make the current approach universal for creating advanced NPs with different combinations of functionalities of the inorganic NPs and radioactive properties of the metal radioisotopes.

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Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET

Cited by 30 publications

References 24 publications

Heat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry

Heat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry

Targeted therapeutics in inflammatory atherosclerosis

Anchoring Group Mediated Radiolabeling for Achieving Robust Nanoimaging Probes

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