In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody

Ding, Ning; Sano, Kohei; Kanazaki, Kengo; Ohashi, Manami; Deguchi, Jun; Kanada, Yuko; Ono, Masahiro; Saji, Hideo

doi:10.1007/s11307-016-0977-2

Cited by 29 publications

(18 citation statements)

References 30 publications

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“…hrUS = high-resolution ultrasonography, μCT = contrast-enhanced in-vivo computed tomography, MRI = 9.4T magnetic resonance imaging, PET = positron emission tomography, BOLD = blood oxygen level dependent, ASL = arterial spin labeling, DCE = dynamic contrast-enhanced, DWI = diffusion-weighted imaging. hrUS μCT 9.4T MRI spatial resolution very high (33 μm) very high (18 μm) high (100 μm) soft tissue contrast good poor very good metastases screening liver bone, lung all organ systems options for functional imaging Doppler 35 , contrast agents 16 , 17 , 36 , photoacoustic imaging 37 contrast agents 20 , combination with PET 38 alternative protocols (BOLD, ASL, DCE, DWI) 23 – 30 , contrast agents 17 , 39 , combination with PET 38 examination time very short (5 minutes) short (12.5 minutes) long (37.9 minutes) radiation exposure none yes (radiation dose depending on protocol and number of scans) none costs (purchase) moderate moderate high …”

Section: Discussionmentioning

confidence: 99%

“…To enable the visualization of the primary tumor as well as the detection of pulmonary or skeletal metastases, the body area scanned included the whole thorax, abdomen and pelvis (oversize scan). Cross-sectional CT images were reconstructed from the acquired radiographs with the “NRecon” Reconstruction software (Bruker Corporation, Billerica, USA) using established protocols 39 . For tumor volume measurement, the “CT An” software (Bruker Corporation, Billerica, USA) was used according to the manufacturers instructions.…”

Section: Methodsmentioning

confidence: 99%

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Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

Linxweiler

Körbel

Müller

et al. 2017

Sci Rep

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In this study, we aimed to comparatively evaluate high-resolution 3D ultrasonography (hrUS), in-vivo micro-CT (μCT) and 9.4T MRI for the monitoring of tumor growth in an orthotopic renal cell carcinoma (RCC) xenograft model since there is a lack of validated, non-invasive imaging tools for this purpose. 1 × 106 Caki-2 RCC cells were implanted under the renal capsule of 16 immunodeficient mice. Local and systemic tumor growth were monitored by regular hrUS, μCT and MRI examinations. Cells engrafted in all mice and gave rise to exponentially growing, solid tumors. All imaging techniques allowed to detect orthotopic tumors and to precisely calculate their volumes. While tumors appeared homogenously radiolucent in μCT, hrUS and MRI allowed for a better visualization of intratumoral structures and surrounding soft tissue. Examination time was the shortest for hrUS, followed by μCT and MRI. Tumor volumes determined by hrUS, μCT and MRI showed a very good correlation with each other and with caliper measurements at autopsy. 10 animals developed pulmonary metastases being well detectable by μCT and MRI. In conclusion, each technique has specific strengths and weaknesses, so the one(s) best suitable for a specific experiment may be chosen individually.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

Linxweiler

Körbel

Müller

et al. 2017

Sci Rep

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“…N87 (human gastric cancer cell) tumor-bearing mice were prepared as reported previously 28 . [ 123 I] 4 -trastuzumab (2.2–4.1 MBq/ 60–150 μg, 150 μL PBS) was intravenously injected into the N87 tumor-bearing mice (n = 3).…”

Section: Methodsmentioning

confidence: 99%

Radioiodination of BODIPY and its application to a nuclear and optical dual functional labeling agent for proteins and peptides

Ono

Watanabe

Ikehata

et al. 2017

Sci Rep

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In molecular imaging research, the development of multimodal imaging probes has recently attracted much attention. In the present study, we prepared radioiodinated BODIPY and applied it as a nuclear and optical dual functional labeling agent for proteins and peptides. We designed and synthesized [125I]BODIPY with a N-hydroxysuccinimide (NHS) ester, and evaluated its utility as a nuclear and fluorescent dual labeling agent for proteins and peptides. In the radioiodination reaction of BODIPY-NHS with [125I]NaI, [125I]BODIPY-NHS was obtained at a 48% radiochemical yield. When we carried out the conjugation reaction of [125I]BODIPY-NHS with bovine serum albumin (BSA) and RGD (Arg-Gly-Asp) peptide as a model protein and peptide, respectively, [125I]BODIPY-BSA and [125I]BODIPY-RGD peptide were successfully prepared at 98 and 82% radiochemical yields, respectively. Furthermore, we prepared [123I]BODIPY-trastuzumab by this conjugation reaction and successfully applied it to single photon emission computed tomography (SPECT) imaging studies using tumor-bearing mice, suggesting that radioiodinated BODIPY-NHS serves as a dual functional labeling agent for proteins and peptides. Since iodine has various radioisotopes that can be used for SPECT and positron emission tomography (PET) imaging, biological research, and radiotherapy, the radioiodinated BODIPY may be extensively applicable from basic to clinical research.

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“…This mode of administration has also been commonly used in other in vivo studies of nanoscale contrast agents with similar NP-size ranges. [33][34][35][36][37] Serum biochemical indices ( Figure 4A) and the results of main blood-cell analysis ( Figure S2) showed that all parameters were within the normal range at each time point. The body weight of mice also played an important role in the biosafety investigation of materials.…”

Section: Biocompatibility and Biodistributionmentioning

confidence: 96%

<p>Targeted Fe-doped silica nanoparticles as a novel ultrasound–magnetic resonance dual-mode imaging contrast agent for HER2-positive breast cancer</p>

Li¹,

Xia²,

Zhou³

et al. 2019

IJN

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Background Multimodal contrast agents with low toxicity and targeted modification have opened up new possibilities for specific imaging of breast cancer and shown broad application prospects in biomedicine and great potential for clinical transformation. In this work, a potential multifunctional imaging agent was developed by doping Fe into hollow silica nanoparticles (HS-Fe NPs), followed by modification with specific anti-HER2 antibodies, enabling the NPs to have dual-mode ultrasound (US)–magnetic resonance (MR)-specific imaging capacity with low toxicity. Methods Anti-HER2 antibodies were conjugated to silane–polyethylene glycol (PEG)–COOH-modified HS-Fe (HS-Fe-PEG) NPs to produce HER2-targeted HS-Fe-PEG (HS-Fe-PEG-HER2) NPs. The toxicity of HS-Fe-PEG-HER2 NPs on targeted cells in vitro and blood and organ tissue of mice in vivo was investigated. Distribution in vivo was also studied. Confocal laser-scanning microscopy and flow cytometry were used to evaluate the targeting ability of HS-Fe-PEG-HER2 NPs in vitro. US and MR instruments were used for imaging both in vivo and in vitro. Results The obtained HS-Fe-PEG-HER2 NPs (average diameter 234.42±48.76 nm) exhibited good physical properties and biosafety. In solution, they showed obvious enhancement of the US signal and negative contrast in T 2 -weighted MR imaging. The binding rate of HS-Fe-PEG-HER2 NPs to targeted cells (SKBR3) was 78.97%±4.41% in vitro. US and MR imaging in vivo confirmed that the HS-Fe-PEG-HER2 NPs were delivered passively into the tumor region of SKBR3 and bound specifically to tumor cells. Target enhancement was better than untargeted and targeted competition groups. Conclusion HS-Fe-PEG-HER2 NPs have potential as a low-cytotoxicity and dual-mode US–MR-specific imaging agent.

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In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody

Abstract: The scFv-IONPs enabled HER2-specific tumor MR imaging, suggesting the potential of scFv-IONPs as a robust HER2-targeted MR contrast agent.

Cited by 29 publications

References 30 publications

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

Radioiodination of BODIPY and its application to a nuclear and optical dual functional labeling agent for proteins and peptides

<p>Targeted Fe-doped silica nanoparticles as a novel ultrasound–magnetic resonance dual-mode imaging contrast agent for HER2-positive breast cancer</p>

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In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody

Abstract: The scFv-IONPs enabled HER2-specific tumor MR imaging, suggesting the potential of scFv-IONPs as a robust HER2-targeted MR contrast agent.

Cited by 29 publications

References 30 publications

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

Radioiodination of BODIPY and its application to a nuclear and optical dual functional labeling agent for proteins and peptides

<p>Targeted Fe-doped silica nanoparticles as a novel ultrasound&ndash;magnetic resonance dual-mode imaging contrast agent for HER2-positive breast cancer</p>

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<p>Targeted Fe-doped silica nanoparticles as a novel ultrasound–magnetic resonance dual-mode imaging contrast agent for HER2-positive breast cancer</p>