Simultaneous SPECT imaging of multi-targets to assist in identifying hepatic lesions

Guo, Zhide; Gao, Mengna; Zhang, Deliang; Li, Yesen; Song, Manli; Zhuang, Rongqiang; X, Su; Chen, Guibing; Liu, Ting; Liu, Pingguo; Wu, Hua; Du, Jianjun; Zhang, Xianzhong

doi:10.1038/srep28812

Cited by 15 publications

(12 citation statements)

References 41 publications

(55 reference statements)

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“…Although these ASGP-R-targeting radiotracers were useful in detecting advanced fibrosis and cirrhosis, they might be not very sensitive in the detection of early and mild fibrosis because they assess liver fibrosis by measuring hepatic function, which did not directly reflect the degree of fibrosis. Furthermore, a series of RGD peptide-based radiotracers had been developed for SPECT imaging by targeting active HSCs 24 , 25 . Regarding HSC-target radiotracers, they could reliably reflect the degree of fibrosis and detect early fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer ^99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

et al. 2018

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Extracellular matrix (ECM) accumulation in liver fibrosis is caused by the activation of hepatic stellate cells (HSCs). The goal of this study was to develop a 99mTc-labeled N-acetylglucosamine (GlcNAc) that specifically interacts with desmin and vimentin expressed on activated HSCs to monitor the progression and prognosis of liver fibrosis using single-photon emission computed tomography (SPECT) imaging.Methods: GlcNAc-conjugated polyethylenimine (PEI) was first prepared and radiolabeled with 99mTc. Noninvasive SPECT imaging with 99mTc-GlcNAc-PEI was used to assess liver fibrosis in a carbon tetrachloride (CCl4) mouse model. The liver uptake value (LUV) of 99mTc-GlcNAc-PEI was measured by drawing the region of interest (ROI) of the whole liver as previously suggested. The LUV of the CCl4 groups was compared with that of the olive oil group. Next, we estimated the correlation between the results of SPECT imaging and physiological indexes. After treatment with clodronate liposome, the LUV of 99mTc-GlcNAc-PEI in fibrotic mice was compared with that in control mice.Results: 99mTc-GlcNAc-PEI is a hydrophilic compound with high radiochemical purity (>98%) and good stability. It could specifically target desmin and vimentin on the surface of activated HSCs with high affinity (the Kd values were 53.75 ± 9.50 nM and 20.98 ± 3.56 nM, respectively). The LUV of 99mTc-GlcNAc-PEI was significantly different between the CCl4 and control groups as early as 4 weeks of CCl4 administration (3.30 ± 0.160 vs 2.34 ± 0.114%/cc; P ˂ 0.05). There was a strong correlation between the LUV and Sirius Red quantification (R = 0.92, P ˂ 0.001). Compared with control, clodronate liposome treatment reduced the LUV of 99mTc-GlcNAc-PEI (4.62 ± 0.352 vs 2.133 ± 0.414%/cc; P ˂ 0.05).Conclusion: 99mTc-GlcNAc-PEI SPECT/CT was useful in assessing liver fibrosis and monitoring the treatment response.

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Section: Discussionmentioning

confidence: 99%

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer ^99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

et al. 2018

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“…Because gamma-emitting radiotracers emit different energies, SPECT provides the option of dual-tracer imaging, for example 99 mTc (149.5 KeV) and 111 In (144 and 218 KeV) have been used to track different SC populations [42,43]. Whereas 111 In offers a longer monitoring window, 99 mTc can be given at higher doses because of its shorter half-life, to improve SNR for higher spatial resolution [14,36].…”

Section: Advantages and Challenges Of Sc Imaging Methods Radionuclidementioning

confidence: 99%

Accomplishments and challenges in stem cell imaging in vivo

Bose

Mattrey

2019

Drug Discovery Today

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“…Labeling anti-NRP-2 mAb with iodine-131. Anti-NRP-2 mAb was labeled with Na 131 I by the chloramine-T method according to a previous study (27). Briefly, in a 1-ml vial, 100 µg anti-NRP-2 mAb was dissolved in 100 µl 0.01 M phosphate-buffered saline (PBS, pH 7.4), followed by the addition of Na 131 I (5.5 MBq 25 µl).…”

Section: Analyses For Anti-nrp-2-specific Antibody and Its Titermentioning

confidence: 99%

131I-labeled monoclonal antibody targeting neuropilin receptor type-2 for tumor SPECT imaging

Chen

Wang

Yan

et al. 2016

International Journal of Oncology

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As a co-receptor for vascular endothelial growth factor‑3 (VEGF‑3), neuropilin receptor type‑2 (NRP‑2) plays a central role in lymphangiogenesis and angiogenesis. Recently, mounting data of evidence show that NRP‑2 is overexpressed in several human cancers, and its overexpression is often associated with poor prognosis. Therefore, it is necessary for us to develop an affinity reagent for noninvasive imaging of NRP‑2 expression because it may be possible to provide early cancer diagnosis, more accurate prognosis, and better treatment planning. Due to their high affinity, and specificity, monoclonal antibodies (mAbs) have been considered attractive candidates for targeted cancer therapy and diagnostics. We recently generated and validated a monoclonal antibody that specifically binds NRP‑2 b1b2 domain with no cross‑reactivity to NRP‑1 b1b2 domain, also known to be overexpressed in a variety of cancers. Here, we developed a single photon emission computed tomography (SPECT) probe for imaging NRP‑2- positive tumors. Anti‑NRP‑2 monoclonal antibodies were prepared by hybridomas and were labeled with iodine‑131 by chloramine‑T method. The in vitro physicochemical properties of 131I‑anti‑NRP‑2 mAb was determined. Binding affinity and specificity of 131I‑anti‑NRP‑2 mAb to NRP‑2 were assessed using human lung adenocarcinoma A549 cells. Biodistribution and SPECT studies were performed in mice bearing A549 tumor xenografts to evaluate the in vivo performance of 131I‑anti‑NRP‑2 mAb. The preparation of anti‑NRP‑2 mAb was completed successfully by hybridoma with high purity (>95%) and specific for NRP‑2 b1b2 domain, but not NRP‑1 b1b2 domain. The radiosynthesis of 131I‑anti‑NRP‑2 mAb was completed successfully within 60 min with high labelling efficiency (94.69±3.63%), and radiochemical purity (98.56±0.48%). The resulting probe, 131I‑anti‑NRP‑2 mAb displayed excellent stability in PBS solution during 24-72 h. 131I‑anti‑NRP‑2 mAb showed high binding affinity with A549 cells (96.6±1.44 nM). In vivo biodistribution and SPECT studies demonstrated targeting of A549 glioma xenografts was NRP‑2 specific. The tumor uptake was 5.86±0.27% ID/g at 6 h, and kept at high level of 4.64±0.82% ID/g at 72 h‑post‑injection. The tumor to contralateral muscle ratio (T/NT) was 2.08±0.33 at 6 h, and reached the highest level of 3.83±0.18 at 72 h after injection. SPECT imaging studies revealed that 131I‑anti‑NRP‑2 mAb could clearly identify A549 tumors with good contrast, especially at 48‑72 h after injection. In conclusion, this study demonstrates that 131I‑anti‑NRP‑2 mAb exhibited highly selective uptake in NRP‑2‑expressing tumors, and may provide a promising SPECT probe for imaging NRP‑2 positive tumors.

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Simultaneous SPECT imaging of multi-targets to assist in identifying hepatic lesions

Cited by 15 publications

References 41 publications

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer ^99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer ^99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

Accomplishments and challenges in stem cell imaging in vivo

131I-labeled monoclonal antibody targeting neuropilin receptor type-2 for tumor SPECT imaging

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Simultaneous SPECT imaging of multi-targets to assist in identifying hepatic lesions

Cited by 15 publications

References 41 publications

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer 99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer 99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

Accomplishments and challenges in stem cell imaging in vivo

131I-labeled monoclonal antibody targeting neuropilin receptor type-2 for tumor SPECT imaging

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Product

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About

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer ^99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer ^99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT