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PET/MRI
CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Flow reactor-based batch production of direct radiolabelable superparamagnetic iron oxide for PET/MRI dual-modality contrast agent

Jie Zhong,Shuang Yan,Yanling Yu,Guihao Hu,Wei Chen,Haiyu Wang,Wenxue Li,Jinping Yuan,Suping Li,Xinghui Li,Xiaoming Zhang,Changqiang Wu

Radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention for their potential in dual-modality imaging, combining positron emission tomography (PET) and magnetic resonance imaging (MRI). The integration provides clinicians with enhanced and complementary imaging information, improving the accuracy of disease diagnosis. However, the complexity of ligand synthesis for functionalization and stable radiolabeling and the difficulty in achieving controlled large-scale production with consistent nanoparticle quality, both of which limit their potential in clinical applications. To overcome these limitations, we report a novel method for preparing SPIONs utilized a simple dual-chelation functional ligand and a continuous synthesis approach to facilitate their clinical translation. The functionalized SPIONs were successfully synthesized by using a flow synthesis technique and the dual-chelation functional ligand (PAsp- g -DA/EA). Compared with traditional synthesis methods, this approach enabled mass production with high reproducibility. The obtained SPIONs showed ultra-small sizes (5.1 ± 0.1 nm), good monodispersity, excellent relaxivity, and superior biocompatibility. The dual-chelation functional ligand enabled direct and efficient radiolabeling of SPIONs with [ 64 Cu]Cu 2+ achieving over 80 % efficiency and outstanding labeling stability. After intravenous injection into rats, high-quality PET and MRI images were obtained. Furthermore, both PET and MRI demonstrated significant nanoprobe accumulation in tumor-bearing mice. In this study, a dual-chelation functional ligand was employed to facilitate the batch and reproducible synthesis of directly radiolabelable SPIONs, thereby addressing key challenges associated with the clinical translation of PET/MRI dual-modality nanoprobes. The nano-probes developed demonstrate excellent biocompatibility, superior imaging efficacy in both PET and MRI, making them potential candidates for medical PET/MRI dual-modality probes.

CAS / MDL: 141-43-5
研究领域: 医学影像学 · 纳米医学 · 放射化学
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2026 · IF 5.2

Construction and application of prostate cancer-targeted PET/MRI contrast agent

Bo Mei,Qichao Zhao,Ruifeng Xue,Xiangxi Meng,Yijun Zhou,Zhi Yang,Lei Xia

Although molecular imaging in nuclear medicine has made remarkable progress, the development of tumor-targeted magnetic resonance imaging (MRI) contrast agents based on tumor-cell–specific targets remains a major challenge. Conventional non-targeted gadolinium chelates such as Gd-DTPA are widely used in clinical MRI but often require high doses to achieve diagnostically meaningful enhancement, and their performance is constrained by modest relaxivity and the lack of tumor-targeting capability. Attempts to introduce targeting ligands onto small-molecule gadolinium complexes may increase molecular complexity, alter pharmacokinetics, and raise biosafety concerns. Meanwhile, superparamagnetic iron oxide nanoparticles have been explored as alternative MRI agents due to their high magnetic sensitivity, yet metal deposition, biodegradation, and long-term retention toxicity continue to hinder clinical translation. Current prostate-specific membrane antigen (PSMA)-targeted PET tracers enable highly sensitive lesion detection, yet a corresponding PSMA-targeted MRI agent capable of providing high-resolution anatomical and functional information is still lacking. Therefore, constructing a true PET–MRI dual-modality nanoplatform is expected to overcome the spatial-resolution limitations of PET alone while compensating for the insufficient molecular specificity of conventional MRI contrast agents. In this study, we developed a novel multifunctional organic nanoplatform based on natural melanin nanoparticles (MNPs). By simply integrating nanocarriers, imaging moiety and targeting ligands within one system, a PSMA-targeted MRI contrast agent was obtained. The PSMA ligand was covalently conjugated onto the surface of PEG-modified MNPs, while large numbers of paramagnetic Gd 3+ ions were chelated/adsorbed onto the melanin scaffold, yielding prostate-cancer-targeted PSMA-GMNs. The hydrodynamic diameters of MNPs and PSMA-GMNs were 3.56 ± 2.09 nm and 15.74 ± 1.63 nm, respectively. PSMA-GMNs exhibited a T 1 -enhancing effect more than five-fold stronger than that of Gd-DTPA in vitro . In vivo MRI demonstrated a high T 1 -weighted signal within LNCaP tumors at 4 h and 24 h post-intravenous administration. Furthermore, 64 Cu-labeled PSMA-GMNs achieved peak tumor uptake at 16 h (SUVmax = 4.24 ± 0.50), indicating sustained PSMA-mediated internalization and prolonged tumor retention. The successfully constructed 64 Cu-PSMA-GMN s achieve functional complementarity between the high-sensitivity molecular detection of PET and the high-resolution anatomical visualization of MRI within a single nano-platform. This work addresses the current lack of prostate-cancer-specific MRI contrast agents and the separation of PET and MRI molecular information in clinical practice.

CAS / MDL: 10138-52-0
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Frontiers in Oncology · 2021 · IF 6.244

Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models

Wen Li,Xia Lei,Guo Xiaoyi,Huang Hai-Feng,Wang Feng,Yang Xian-teng,Yang Zhi,Zhu Hua

Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.

研究领域: 肿瘤学 · 分子影像 · 纳米医学 · 癌症治疗
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