Citation: Xia Lei, Cheng Zhen, Zhu Hua, Yang Zhi. Preparation and Preliminary Molecular Imaging Study of ¹²⁴I in-situ Labeled Organic Melanin Nanoparticles[J]. Acta Chimica Sinica, ;2019, 77(2): 172-178. doi: 10.6023/A18090410 shu

Preparation and Preliminary Molecular Imaging Study of ¹²⁴I in-situ Labeled Organic Melanin Nanoparticles

Xia Lei ^a ,
Cheng Zhen ^b ,
Zhu Hua ^a,, ,
Yang Zhi ^a,,

a.
Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142
b.
Molecular Imaging Program at Stanford(MIPS) and Bio-X Program, Department of Radiology, School of Medicine, Stanford University, Stanford, California, 94305

Corresponding author: Zhu Hua, zhuhuananjing@163.com Yang Zhi, pekyz@163.com
Received Date: 29 September 2018
Available Online: 3 March 2018
Fund Project: Project supported by the National Natural Science Foundation of China (Nos. 81671733, 81501519 and 81571705) and Beijing Nova program (No. Z171100001117020)the National Natural Science Foundation of China 81571705Beijing Nova program Z171100001117020the National Natural Science Foundation of China 81501519the National Natural Science Foundation of China 81671733

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Developing biocompatible, multifunctional and in-situ labeling nanoplatform is high challenging for molecular imaging. Organic derivates melanin nanoparticles (MNPs) holds great potential to be multimodal contrast agents, and have been used for photoacoustic imaging, magnetic resonance imaging, and ⁶⁴Cu PET imaging with simple modifications. In order to extend MNPs application in molecular imaging, here a novel radio-nuclide was applied to in-situ labeling of MNPs. Large numbers of active dihydroxyindole/indolequinone groups and natural binding ability of MNPs enabled them to have the ability to label different types of radionuclides which have unique half-life and functions, especially long-life elemental nuclide. This project explored the in-situ labeling methods of organic melanin nanoparticles with a promising diagnostic radionuclides named Iodine-124 (¹²⁴I), and using this novel multifunctional organic nanoparticles for preliminary molecular imaging studies. Generally, ultrafine particle size melanin nanoparticles (5.5 nm in diameter) were prepared by ultrasonication method using naturally occurring melanin, then PEG₃₅₀₀ which had amino group at both ends was used as a stabilizer agent to obtain PEG-MNP nanocarriers (7.5 nm in diameter) with better water solubility and stability. The nanoparticles were full characterized by dynamic light scattering (DLS), transmission electron microscope (TEM) and ¹H NMR, respectively. Then, one kind of elemental nuclide was labeled. Classic iodine labeled method with N-Bromo Succinimide (NBS) was used as oxidant to oxidize active dihydroxyindole/indolequinone ring of PEG-MNP for electrophilic substitution reaction labeling ¹²⁴I (100.8 h). This reaction rate is extremely fast (60 s reaction time) and high labelling yield (>99%). The ¹²⁴I was labeled successfully and in-situ labeled PEG-MNP nanocarriers were obtained. After that, ¹²⁴I and ¹²⁴I-PEG-MNP were used to further preclinical evaluation by micro-PET imaging. Micro-PET images were collected at 2 h, 24 h and 48 h after intravenous injection 7.4 MBq ¹²⁴I and ¹²⁴I-PEG-MNP in normal Kunming mice (n=3). The ROI target area of heart, liver and thyroid were delineated for semi-quantitative analysis. Then, in order to verify the imaging ability of ¹²⁴I-PEG-MNP in solid tumor. We built human pancreatic cancer BxPC3 xenograft model (n=3), and Micro-PET scans were performed at different time points. Results showed that the labeling rate of ¹²⁴I on PEG-MNP was 99.9%. And the radiochemical purity in vitro stability of ¹²⁴I-PEG-MNP in 96 h was more than 90%. Micro-PET images showed that ¹²⁴I-PEG-MNP had no obvious thyroid uptake which indicated no de-marking in mice. The radio-distribution of ¹²⁴I and ¹²⁴I-PEG-MNP was substantially different in liver and thyroid (P < 0.001). In vivo semi-quantitative analysis showed that the radio uptakes of organs were consistent with the distribution of nanoparticles. And the PET imaging of xenograft mice showed that ¹²⁴I-PEG-MNP can utilize the enhanced permeability and retention effect (EPR) to be significantly enriched at the tumor and retained in the tumor site for more than 48 h. PEG-MNP has the ability to label long half-life nuclide ¹²⁴I. This research provides an experimental basis for further construction of long-circulation multimodal imaging probes.
- melanin nanoparticles,
- polynuclear labeled,
- molecular imaging,
- in-situ labeling,
- Micro-PET
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Preparation and Preliminary Molecular Imaging Study of 124I in-situ Labeled Organic Melanin Nanoparticles

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通讯作者: 陈斌, bchen63@163.com

Preparation and Preliminary Molecular Imaging Study of ¹²⁴I in-situ Labeled Organic Melanin Nanoparticles