Recommendations on Strengthening the Development of Nuclear Medicine in China

This paper outlines briefly the role of nuclear medicine in life sciences and health care. Molecular imaging by using isotopic tracers can noninvasively visualize the chemistry or hidden process in the cells and tissues inside the body, obtaining "functional" images to provide early information of any disease and revealing the secrets of life. The vitality of nuclear medicine is its ability to translate bench into new clinical application that can benefits the patients. Although nuclear medicine community in China has made significant achievement with a great effort since 1950s, there are many obstacles to future development. Recommended measures are proposed here in an attempt to solve our existing problems.

Preparation and biodistribution of ^(99)Tc^m-PIDP as bone imaging agent

A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in conditions of 0.1 mg SnCl2.2H2O at pH 6.0 and 99TcmO4? in aqueous solution for 20 min at room temperature. The labeling yield and radiochemical purity of 99Tcm-PIDP are both higher than 95%. The biodistribution results show that the bone uptake is up to 8.47% ID/g which is the maximum of bone uptake at 30 min after injection of 99Tcm-PIDP in mice. The pharmacokinetic parameters can be estimated from the exponential equation of C=59.565e-11.307t+2.069e-1.211t. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-PIDP. The results indicate that 99Tcm-PIDP has highly selective uptake in the skeletal and low uptake, rapid clearance in soft tissues, so it would be a potential novel bone imaging agent.

^(18)F-fluoromisonidazole positron emission tomography may be applicable in the evaluation of colorectal cancer liver metastasis

Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.

Synthesis and biological evaluation of ^(18)F-FB-NGA as a hepatic asialoglycoprotein receptor PET imaging agent

Asialoglycoprotein receptor(ASGP-R)is a hepatic membrane receptor that uniquely exists on the surface of mammalian hepatocytes,and has been used as target of liver functional imaging agents for many years.We labeled the Galactosyl-neoglycoalbumin(NGA)with 18F to get a PET molecular probe 18F-FB-NGA and evaluated its ability as a liver functional PET imaging agent.The 18F-FB-NGA was prepared with NGA by conjugation with Nsuccinimidyl-4-18F-fluorobenzoate(18F-SFB)and purified with PD-10 desalting column.The radiolabeling yield and radiochemical purity of 18F-FB-NGA were determined by radio-HPLC.Starting with 18F-F–,the total time for 18F-FB-NGA was about 120±10 min.The decay-corrected radiochemical yield is about 25–30%.The radiochemical purity of purified 18F-FB-NGA was more than 98%.Labeled with 185–1850 MBq 18F-SFB,the specific activity of 18F-FBNGA was estimated to be 7.83–78.3 TBq/mmol.Biodistribution of 18F-FB-NGA in normal mice was investigated after injection through the tail vein.The results showed that the liver accumulated 39.47±3.42 and 12.12±6.11%ID/g at 10 and 30 min after injection,respectively.Dynamic MicroPET images in mice were acquired with and without block after injection of the radiotracer,respectively.High liver activity accumulation was observed at 5 min after injection in normal group.On the contrary,the liver accumulation was significantly lower after block,indicating the specific binding to ASGP-R.18F-FB-NGA is probably a potential PET liver imaging agent.

Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer

Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,^(68)Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer ^(68)Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.

Prediction of tumor biological characteristics in different colorectal cancer liver metastasis animal models using^(18)F-FDG and^(18)F-FLT

Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.

Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.

Preparation and preliminary biological evaluation of ^(99m)Tc-ANMdU

Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl]amino}-methyl-2′-deoxy- uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates were verified with MS and 1HNMR. Using SnCl2 as reducing agent, a labeling reaction was carried out at 100°C for 30 min. The radiochemical purity of the 99mTc-ANMdU was 96.68%. Partition coefficients were 0.92 and 0.70 at pH 7.0 and 7.4 of the phosphate buffer saline, respectively. Biodistribution of 99mTc-ANMdU in normal mice showed that the initial uptake of 99mTc-ANMdU in vivo and the clearance was rapid.

Semi-synthesis and Crystal Structure of Sophoridine N-oxide

Sophoridine N-oxide was synthesized and characterized by 1H-NMR,EI-MS,IR and elemental analysis,together with X-ray single-crystal diffraction analysis,and its crystal structure was reported for the first time.The crystal belongs to the orthorhombic system,space group P212121 with a = 8.321（2）,b = 15.650（3）,c = 24.352（5） ,V = 3171.1（11） 3,Z = 8,Dc = 1.258 g/cm3,λ（CuKα） = 1.54178,F（000） = 1440,the final R = 0.0351 and wR = 0.0970.The crystal structure shows Sophoridine N-oxide crystallizes with two host molecules of similar conformation and four water solvent molecules in the asymmetric unit.In the crystal structure,intermolecular O-H…O hydrogen bonds link the constituent molecules into a 2D layer structure,which further extends to a 3D supramolecular architecture via Van der Waals interactions and intermolecular O-H…O hydrogen bonds.

Near-infrared fluorescent labeled CGRRAGGSC peptides for optical imaging of IL-11Rα in athymic mice bearing tumor xenografts

The interleukin-11(IL-11)and the IL-11 receptorα-subunit(IL-11Rα)have been demonstrated to regulate the invasion and proliferation of tumor cells.Our study intends to evaluate a noninvasive imaging of IL-11Rαexpression in breast tumors using near-infrared(NIR)fluorescent dye Cy7-labeled IL-11 mimic peptide CGRRAGGSC.This work evaluated the IL-11Rαexpression of breast tumor cells and the binding status of this peptide to IL-11Rαin vitro and in vivo by using Western blotting,immunofluorescence staining and near-infrared fluorescence imaging.Our biochemical study showed that IL-11Rαwas overexpressed in breast tumor cells(MCF-7).The cell-binding assay demonstrated specific binding of peptide CGRRAGGSC to MCF-7 cells in vitro.In vivo imaging results showed that NIR fluorescent signals of Cy7-CGRRAGGSC were selectively accumulated in tumor and metabolic organs.While in the blocking experiment,free CGRRAGGSC obviously blocked the concentration of the Cy7-CGRRAGGSC in the tumors.These results suggested that IL-11Rαmay be used as a potential target for noninvasive imaging in IL-11Rαoverexpressed tumors.Furthermore,the imaging agent of near-infrared fluorescent dye Cy7-labeled CGRRAGGSC is suitable for IL-11Rαexpression imaging study in vivo.

Preparation of ^(99m)Tc-PQQE and preliminary biological evaluation for the NMDA receptor

The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stannous fluoride (SnF 2 ) as reducing agent. Biological characteristics of 99m Tc-PQQE include lipophilic and the charge properties were compared to 99m Tc-PQQ. The biodistributions of 99m Tc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99m Tc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2β) results indicate that the residence time of 99m Tc-PQQE (203.92) in the body is twice as long as 99m Tc-PQQ (100.45). The uptake of 99m Tc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99m Tc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99m Tc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99m Tc-PQQE has some specific targeting to the NMDA receptor.

Study on the reaction kinetics of ^(99)Tc^m-labeled BIDP

A novel zoledronic acid derivative,1-hydroxy-2-(2-butyl-1H-imidazole-1-yl)-ethylidene-l,l- diphosphonic acid(BIDP),was synthesized and labeled with ^(99)Tc^m.The detailed kinetic study on the labeling reaction between BIDP and ^(99)Tc^m was carried out.The results indicated that the reaction rate constants k were 0.0258,0.0268, 0.0305,0.0323,0.0351 and 0.0384 min^(-1)at 0℃,5℃,10℃,15℃,20℃and 25℃,respectively.From the Arrhenius equation k=A·e^(-E_Δ/(RT)),the activation energy E_a of the labeling reaction was calculated to be 10.45 kJ/mol.And the correlation between k and temperature(T)was also deduced as In k=-1258.8×(l/T)+0.9531.In addition,it was found that in order to get a high radiolabeling yield(RLY)(>90%),the reaction temperature must be up to 12℃.

Biological characteristics of [^(18)F]-THK523 for tau imaging

Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer's disease(AD). The existence of neurofibrillary tangles(NFTs) consisting of tau protein are one kind of the pathological features of AD, and its level of severity is correlated with the stage of AD.However, no clinically approved positron emission tomography(PET) probe is currently available for selective imaging of neurofibrillary tangles on patients. In this paper, we report our studies on biological characteristics of [18F]-THK523 as a novel tau imaging probe. With low molecular weight, [18F]-THK523 is stable, electrically neutral, lipophilic and non-mass concentration-dependent. Preliminary biological studies have shown the excellent properties of [18F]-THK523 as brain imaging tracer for further research.

Improved preparation and chemical kinetics on fully automated synthesis of [^(18)F]-THK523,a PET imaging probe for Tau pathologies

Extensive accumulation of neurofibrillary tangles(NFTs)consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer's disease.However,no PET probe is currently available for selective detection of NFTs in the living human brain.[^(18)F]-THK523 was developed as a potential in vivo imaging probe for tau pathology.In this paper,we report a new protected precursor,2-((2-(4-((tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(THK-7),instead of2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(BF241),and an improved automated radiosynfhesis of[^(18)F]-THK523 and the study on chemical kinetics of the labeling reaction of[^(18)F]-THK523,with high-yield(70±5%,n=6,decay-corrected to end of bombardment),and high radiochemical purity(>90%)and specific activity(2.5±0.5Ci/umol)from protected precursor on fully automated module at the end of radiosynthesis(45-55 min).The chemical kinetics for[^(18)F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.

Semi-automated synthesis,validation and microPET imaging of ^(18)F-FP-DTBZ as a vesicular monoamine transporter ligand

This work was to develop a semi-automated synthesis of 18F-9-fluoropropyl-9-desmethyl-DTBZ (18F-FP-DTBZ) and validate its potential as a vesicular monoamine transporter 2 (VMAT2) ligand.18F-FP-DTBZ was synthesized by a semi-automated procedure in a 21-35% yield without decay correction and with a radiochemical purity of >98%.Bioistribution in rats exhibited a favorable brain uptakes of the ligand (0.31±0.04 ID% at 60min post injection,n=8).The highest radioactivity located in VMAT2 enriched striatal tissue.The target-to-nontarget ratio (striatum/cerebellum,ST/CB) was 4.81±0.84.Blocking studies implied that striatum uptake could be blocked by DTBZ (a VMAT2 inhibitor) but could not by CFT (a dopamine transporter inhibitor).MicroPET imaging with 18F-FP-DTBZ in normal rats gave high quality images in which high radioactivity were observed in the striatal tissue.Time-and-activity curves revealed good retention in the target (striatum) and rapid clearance in the background (cerebellum),which resulted in a maximum ST/CB ratio of 5.08±0.81 (n=3) in 80-120min.By contrast,the 6-hydroxydopamine unilateral lesioned rats gave asymmetrical striata images with higher 18F-FP-DTBZ concentration on the unlesioned side (unlesioned-ST/CB=5.21±0.38,n=3) than the lesioned (lesioned-ST/CB=2.34±0.51).The results validated that 18F-FP-DTBZ is a favorable PET ligand binding to VMAT2.

Study of chemical kinetics on labeling of ^(99m)Tc-N-ethyl-N_2S_2-Memantine

In this work,a calculation method of chemical kinetics was established for labeling reaction of 99mTc-N-ethyl-N2S2-memantine,a potential NMDA receptor imaging agent prepared in our laboratory.Four groups of vials (3 vials per group) were added with 0.02 mL (1 mg/mL) N-ethyl-N2S2Memantine,0.08 mL (40 mg/mL) GH,0.05 mL (10 mg/mL) EDTA-2Na,0.035 mL (2 mg/mL) SnF2,0.8 mL phosphate buffer(1mol/L,pH 6.5) and 37 MBq Na99mTcO4.The vials were incubated at 70℃,80℃,90℃ or 100℃.Samples were taken with capillary from the vials at 2,5,10,20,30,40 and 60min.Labeling yields were determined by TLC.Order of reaction n,rate constant k,activation energy Ea and half life t1/2 of labeling reaction were calculated with the kinetics software we compiled.Mean labeling yields of 99m Tc-N-ethyl-N2S2-memantine at 2,5,10,20,30,40 and 60min were (1) 13.5,15.7,34.0,64.8,81.9,91.4 and 95.4 at 70℃;(2) 13.2,20.5,40.1,70.0,88.2,94.5 and 95.6 at 80℃;(3) 15.6,22.9,43.7,74.3,87.2,93.4 and 96.1 at 90℃;and (4) 20.5,25.8,45.3,81.1,92.2,95.6 and 96.0 at 100℃.The other parameters were;n =1;k=0.053,0.061,0.063 and 0.076 L/min at 70℃,80℃,90℃ and 100℃,respectively;Ea=12.38 kJ/L;t1/2=13.11,11.45,11.05 and 9.07min at 70℃,80℃,90℃ and 100℃,respectively.The mean labeling yield increased with temperature and time,optimized at 100℃ and 40-60min.The concentration of 99mTc-N-ethyl-N2S2-Memantine was larger than that of Na99mTcO4,so n=1.The k increased with reaction,hence the accelerated reaction rate at higher temperatures.The labeling reaction was not so difficult because of the low Ea.The t1/2 decreased with increasing reaction temperature,hence the acceleration of labeling reaction.

Synthesis and Crystal Structure of 2-(2-Ethyl-1H-imidazol-1-yl)-1-hydroxy- ethane-1,1-diyldiphosphonic Acid (EIHDP)

The crystal structure of the title compound （C7H14N2O7P2, Mr = 300.14） was determined by single-crystal X-ray diffraction. The crystal belongs to triclinic, space group P1 with a = 8.258（3）, b = 8.886（3）, c = 9.275（3） A, a = 96.669（3）, β = 115,706（3）, γ= 104.467（3）°, V= 573.8（3） A^3, Z = 2, Dc = 1.737 g/cm^3, 2（MoKa） = 0.71073, F（000） = 720,μ（MoKa） = 0.41 mm^-1 R = 0.030 and wR = 0.078. A total of 1970 unique reflections were collected, of which 1742 with I 〉 2σ（I） were observed. EIDHP has a structure similar to zoledronic acid （ZL）. ZL is a potent bone antiresorptive bisphosphonate drug having significant activity against several parasitic protozoa. EIHDP has inner-salt character, consisting of a negatively charged PO3 group and a positively charged N（1） atom. The crystal structure is stabilized by interrnolecular hydrogen bonds of O-H…O and N-H…O.

Assessment of tumor response to chemotherapy in patients with breast cancer using ^(18)F-FLT: a meta-analysis

Purpose： To determine the diagnostic performance of 3＇-deoxy-3＇-18F-fluorothymidine positron emission tomography/computed tomography（FLT PET/CT） and FLT PET for evaluating response to chemotherapy in patients with breast cancer.Methods： Databases such as Pub Med（MEDLINE included） and excerpta medica database（EMBASE）, were searched for relevant original articles. The included studies were assessed for methodological quality with quality assessment of diagnosis accuracy studies（QUADAS） score tool. Histopathological analysis and/or clinical and/or radiological follow-up for at least 6 months were used as the reference standard. The data were extracted by two reviewers independently to analyze the sensitivity, specificity, summary receiver operating characteristic（SROC） curve, area under the curve（AUC）, and heterogeneity.Results： The present study analyzed a total of 4 selected articles. The pool sensitivity was 0.773 [95% confidence interval（CI）： 0.594-0.900]. The pooled specificity was 0.685（95% CI： 0.479-0.849） on basis of FEM. The pooled LR^＋, LR^-, and DOR were 2.874（1.492-5.538）, 0.293（0.146-0.589）, and 14.891（3.238-68.475）, respectively. The AUC was 0.8636（±0.0655）, and the Q＊ index was 0.7942（±0.0636）.Conclusions： Our results indicate that 18^F-FLT PET/CT or PET is useful to predict chemotherapy response in breast cancer with reasonable sensitivity, specificity and DOR. However, future larger scale clinical trials will be needed to assess the regimen of 18^F-FLT PET/CT or PET in monitoring the response to chemotherapy in breast cancer patients.

In vivo SPECT imaging of an 131I-labeled PM 2.5 mimic substitute

The health effects of ambient PM 2.5 and its potential mechanisms have generated considerable interest.In vitro cell studies and ex vivo animal experiments may not accurately determine the characteristics of PM 2.5 particles.To better understand their detailed mechanisms,we performed an in vivo study using single photon emission tomography(SPECT)imaging.To mimic the PM 2.5 particles,SiO2 nanoparticles modified by ethylene carbonate or polyvinyl pyrrolidone were labeled with 131I.After administration via inhalation,in vivo SPECT imaging of the radiolabeled particles in sprague dawley rats was performed.It was found that radioactivity accumulated in the lungs and trachea 6 and 24 h after administration.In addition,significant radioactivity was observed in the abdomen,including the liver and kidneys.The results were also confirmed by ex vivo autoradiography.This study revealed that in vivo SPECT imaging could be an effective method for investigating the properties of PM 2.5 particles.

Melanin-based nanoparticles in biomedical applications:From molecular imaging to treatment of diseases

Melanin nanoparticles(MNPs) is a kind of natural nanomaterial, not only retain the inherent characteristics of melanin(metal ion chelation, photothermal conversion property, etc.) but also can exhibit more excellent properties, such as high dispersion stability, good biocompatibility and biodegradability. Furthermore, these performances can be enhanced to target the specific sites and treat diseases by the surface modification or combination with functional substance. All these advantages of MNPs made it an ideal platform for developing biomedical applications. In this paper, the MNPs preparation methods were summarized first. Biomedical applications of MNPs were also reviewed,including molecular imaging(magnetic resonance, positron emission tomography, and photoacoustic imaging) and treatment of diseases(drug delivery, photothermal therapy, antioxidant therapy, and iron overload therapy). Further development and prospects of MNPs for practice in biology or medicine were also discussed.