1.Advancements in molecular imaging probes for precision diagnosis and treatment of prostate cancer.
Jiajie FANG ; Ahmad ALHASKAWI ; Yanzhao DONG ; Cheng CHENG ; Zhijie XU ; Junjie TIAN ; Sahar Ahmed ABDALBARY ; Hui LU
Journal of Zhejiang University. Science. B 2025;26(2):124-144
Prostate cancer is the second most common cancer in men, accounting for 14.1% of new cancer cases in 2020. The aggressiveness of prostate cancer is highly variable, depending on its grade and stage at the time of diagnosis. Despite recent advances in prostate cancer treatment, some patients still experience recurrence or even progression after undergoing radical treatment. Accurate initial staging and monitoring for recurrence determine patient management, which in turn affect patient prognosis and survival. Classical imaging has limitations in the diagnosis and treatment of prostate cancer, but the use of novel molecular probes has improved the detection rate, specificity, and accuracy of prostate cancer detection. Molecular probe-based imaging modalities allow the visualization and quantitative measurement of biological processes at the molecular and cellular levels in living systems. An increased understanding of tumor biology of prostate cancer and the discovery of new tumor biomarkers have allowed the exploration of additional molecular probe targets. The development of novel ligands and advances in nano-based delivery technologies have accelerated the research and development of molecular probes. Here, we summarize the use of molecular probes in positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound imaging, and provide a brief overview of important target molecules in prostate cancer.
Humans
;
Male
;
Prostatic Neoplasms/diagnosis*
;
Molecular Probes
;
Molecular Imaging/methods*
;
Magnetic Resonance Imaging
;
Positron-Emission Tomography
;
Tomography, Emission-Computed, Single-Photon
;
Ultrasonography
;
Optical Imaging
;
Biomarkers, Tumor
;
Precision Medicine/methods*
2.Application of molecular probes in nuclear imaging of neuroendocrine tumors.
Jing YAN ; Tingting ZHANG ; Kui ZHAO
Journal of Zhejiang University. Medical sciences 2021;50(1):131-137
Neuroendocrine tumors are a type of heterogeneous tumors originating from neuroendocrine cells derived from the neural crest,which can secrete a variety of amines and peptide hormones.Based on different molecular biomarkers,histologic types and differentiation degrees,individualized nuclear imaging can provide information for the early diagnosis,clinical staging,treatment guidance,and detection of the recurrence and metastasis of neuroendocrine tumor. In this paper,we review the development and application of nuclear medicine molecular imaging probes such as glucose analogs,somatostatin analogues,amine precursors,hormone analogs and enzyme inhibitors in the diagnosis and treatment of neuroendocrine tumors.
Diagnostic Imaging
;
Humans
;
Molecular Probes
;
Neoplasm Recurrence, Local
;
Neuroendocrine Tumors/diagnostic imaging*
;
Radionuclide Imaging
3.Improved synthesis process of optical-magnetic bimodal probe of Gd-4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl-acetic acid complexes.
Hui SHENG ; Lei LIANG ; Tong Liang ZHOU ; Yan Xing JIA ; Tong WANG ; Lan YUAN ; Hong Bin HAN
Journal of Peking University(Health Sciences) 2020;52(5):959-963
OBJECTIVE:
To improve the methods to synthesize and purify of optical-magnetic bimodal molecular probe of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluorescein thioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes.
METHODS:
Target compound (7), optical-magnetic bimodal molecular molecular probe, was synthesized by the use of 1, 4, 7, 10-tetraazacyclododecane (1) as starting material via substitution reaction, hydrolysis reaction, coupling reaction and complexation reaction with metal.
RESULTS:
The synthetic route of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes was improved. The optical-magnetic bimodal molecular probes were synthesized by substitution reaction, hydrolysis reaction, coupling reaction and complex reaction with metal respectively. For the improved route, the total yield could reach 34.6% which was higher than the original route (18.0%). The structures of those compounds were identified by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and mass spectrometry. The improved route could avoid the uncontrollable disadvantage of the substitution reaction, this process could reduce the formation of impurities and made the purification process easier, and in the aspect of purification and separation, the preparative high-performance liquid chromatography with less sample loading and high cost was improved to a column chromatography with many sample loads and being easy to operate. Therefore, the use of column chromatography could be more conducive to mass production of the optical-magnetic bimodal molecular molecular probe.
CONCLUSION
The improved synthetic route improves the controllability of the reaction conditions and makes it easier to purify and separate the compounds. At the same time, the improved synthetic route can increase the total yield significantly. The optical-magnetic bimodal molecular probe can combine the living magnetic resonance imaging with the in vitro optical imaging to realize the dual synchronous detection of magneto-optics, so that the detection results of the living magnetic resonance imaging and the in vitro optical imaging are mutually verified. In other words, this synthetic optical-magnetic bimodal molecular probe will make the experimental results more accurate and reliable. In subsequent biological experimental studies, the optical-magnetic bimodal molecular probe can be applied to related research of brain structure and function, and the probe can be used for the brain-related diseases researches, such as brain tumors. after intravenous administration, and thus the optical-magnetic bimodal molecular probe can play an important role in medical treatment of brain tumors and cerebrovascular diseases.
Acetic Acid
;
Brain
;
Magnetic Resonance Imaging
;
Magnetic Resonance Spectroscopy
;
Molecular Probes
4.Review: optically-triggered phase-transition droplets for photoacoustic imaging.
Qiyang CHEN ; Jaesok YU ; Kang KIM
Biomedical Engineering Letters 2018;8(2):223-229
Optically-triggered phase-transition droplets have been introduced as a promising contrast agent for photoacoustic and ultrasound imaging that not only provide significantly enhanced contrast but also have potential as photoacoustic theranostic molecular probes incorporated with targeting molecules and therapeutics. For further understanding the dynamics of optical droplet vaporization process, an innovative, methodical analysis by concurrent acoustical and ultrafast optical recordings, comparing with a theoretical model has been employed. In addition, the repeatability of the droplet vaporization-recondensation process, which enables continuous photoacoustic imaging has been studied through the same approach. Further understanding the underlying physics of the optical droplet vaporization and associated dynamics may guide the optimal design of the droplets. Some innovative approaches in preclinical studies have been recently demonstrated, including sono-photoacoustic imaging, dual-modality of photoacoustic and ultrasound imaging, and super-resolution photoacoustic imaging. In this review, current development of optically triggered phase-transition droplets and understanding on the vaporization dynamics, their applications are introduced and future directions are discussed.
Methods
;
Models, Theoretical
;
Molecular Probes
;
Theranostic Nanomedicine
;
Ultrasonography
;
Volatilization
5.Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space.
Yun Qian LI ; Hui SHENG ; Lei LIANG ; Yue ZHAO ; Huai Ye LI ; Ning BAI ; Tong WANG ; Lan YUAN ; Hong Bin HAN
Journal of Peking University(Health Sciences) 2018;50(2):221-225
OBJECTIVE:
To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA-FITC) in brain tissue imaging and brain interstitial space (ISS).
METHODS:
In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups.
RESULTS:
For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10-4 mm2/s vs. (3.37±0.15)×10-4 mm2/s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177], the diffusion areas [(23.25±0.68) mm2 vs. (22.71±1.00) mm2, t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC [(22.61±1.16) mm2] was slightly larger than that of FITC [(22.10±1.29) mm2], the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492).
CONCLUSION
Gd-DO3A-EA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.
Animals
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Brain/diagnostic imaging*
;
Caudate Nucleus
;
Contrast Media
;
Diffusion
;
Fluorescein-5-isothiocyanate
;
Fluorescence
;
Gadolinium DTPA
;
Imaging, Three-Dimensional
;
Magnetic Resonance Imaging
;
Male
;
Microscopy, Confocal
;
Molecular Probes
;
Rats
;
Rats, Sprague-Dawley
6.Advances in the Endoscopic Assessment of Inflammatory Bowel Diseases: Cooperation between Endoscopic and Pathologic Evaluations.
Journal of Pathology and Translational Medicine 2015;49(3):209-217
Endoscopic assessment has a crucial role in the management of inflammatory bowel disease (IBD). It is particularly useful for the assessment of IBD disease extension, severity, and neoplasia surveillance. Recent advances in endoscopic imaging techniques have been revolutionized over the past decades, progressing from conventional white light endoscopy to novel endoscopic techniques using molecular probes or electronic filter technologies. These new technologies allow for visualization of the mucosa in detail and monitor for inflammation/dysplasia at the cellular or sub-cellular level. These techniques may enable us to alter the IBD surveillance paradigm from four quadrant random biopsy to targeted biopsy and diagnosis. High definition endoscopy and dye-based chromoendoscopy can improve the detection rate of dysplasia and evaluate inflammatory changes with better visualization. Dye-less chromoendoscopy, including narrow band imaging, iScan, and autofluorescence imaging can also enhance surveillance in comparison to white light endoscopy with optical or electronic filter technologies. Moreover, confocal laser endomicroscopy or endocytoscopy have can achieve real-time histology evaluation in vivo and have greater accuracy in comparison with histology. These new technologies could be combined with standard endoscopy or further histologic confirmation in patients with IBD. This review offers an evidence-based overview of new endoscopic techniques in patients with IBD.
Biopsy
;
Diagnosis
;
Endoscopy
;
Humans
;
Inflammatory Bowel Diseases*
;
Microscopy, Confocal
;
Molecular Probes
;
Mucous Membrane
;
Narrow Band Imaging
;
Optical Imaging
7.Pharmacokinetics and MR imaging of SPIO-shRNA dual functional molecular probe in vivo.
Xiao-lin DENG ; Xiao-dong GE ; Xiao-feng WU ; Mei-ling LI ; Rui-kun LIAO ; Dan-ni ZENG ; Ming WEN
Acta Pharmaceutica Sinica 2015;50(10):1285-1289
In this study, we investigated the pharmacokinetics parameters of SPIO-shRNA dual functional molecular probe and observed the main organ distribution by MRI in vivo. Eighteen New Zealand white rabbits were randomly divided into three groups and injected intravenously with different doses of SPIO-shRNA molecular probe, respectively. The blood samples were collected to analyze the pharmacokinetic parameters by measuring the iron content at 30 minutes before and after the injection. Twenty-four Kun Ming (KM) mice were randomly divided into 4 groups: the control group was injected intravenously with physiological saline 200 µL per mouse via the tail vein, the other 3 groups were injected intravenously with different doses of SPIO-shRNA molecular probe. MRI observation was performed in 24 hours, and the liver, spleen, kidney, brain and muscle were collected for iron quantification with Prussian blue staining to determine distribution of the SPIO-shRNA molecular probe in the main organ in vivo. Our results suggest that the molecular probe blood half-life is more than 3 hours. The data of MRI suggest the probe was distributed in liver and spleen, and the MRI signal was reduced with the increase in probe's doses (P < 0.05). The results of Prussian blue staining confirmed the results of MRI. Most of the probe could escape the phagocytosis of mononuclear phagocyte system. Our data provide the pharmacokinetic and distribution of SPIO-shRNA molecular probe in organs. Meanwhile, it suggests the choice of the time and dose of probe for MR imaging of tumor in vivo.
Animals
;
Half-Life
;
Magnetic Resonance Imaging
;
Magnetite Nanoparticles
;
Mice
;
Molecular Probes
;
pharmacokinetics
;
RNA, Small Interfering
;
chemistry
;
Rabbits
8.Effects of external magnetic field on the transfection rate of SPIO-shRNADual functional molecular probe into ovarian carcinoma SKOV3 cells in vitro.
Xiao-dong GE ; Mei-ling LI ; Xiao-lin DENG ; Xiao-feng WU ; Dan-ni ZENG ; Rui-kun LIAO ; Ming WEN ; Shao-lin LI
Acta Academiae Medicinae Sinicae 2015;37(1):12-16
OBJECTIVETo explore the transfection rate of SPIO-shRNA dual functional molecular probe into ovarian carcinoma SKOV3 cells in external magnetic field.
METHODSDual functional molecular probe at an iron concentration of 45 mg/L was transfected into SKOV3 cells. The cells with coexisting probe and magnetic fields were set as the intervention group,the probe-transfected cells as negative control group, and normally cultured SKOV3 without any transfection as blank control group. The transfection rate was detected by flow cytometry. Cell viability was observed by CCK-8 assay. Epidermal growth factor receptor (EGFR) expression level in SKOV3 cells was determined by real-time quantitative PCR and Western blot analysis. The signal intensity was measured by magnetic resonance imaging (MRI).
RESULTSThe transfection rate of the intervention group was (79.20 ± 3.31)%, which was significantly higher than that of negative control group (P=0.001). Compared with the negative control group,the cell viability of the intervention group significantly decreased (P=0.011), protein and mRNA expression levels of EGFR in the intervention group were significantly decreased (both P<0.05). The signal intensity on T2(*)WI in the intervention group also significantly decreased (P=0.0004).
CONCLUSIONThe external magnetic field can improve the transfection efficiency SPIO-shRNA dual functional molecular probe into ovarian carcinoma SKOV3 cells.
Blotting, Western ; Cell Line, Tumor ; Cell Survival ; ErbB Receptors ; Female ; Flow Cytometry ; Humans ; In Vitro Techniques ; Iron ; Magnetic Fields ; Molecular Probes ; Ovarian Neoplasms ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Transfection
9.Progress in the study of near-infrared fluorescent probes for the detection of β-amyloid deposition in Alzheimer's disease.
Lei DU ; Hai-wei FENG ; Yu-yan LI
Acta Pharmaceutica Sinica 2015;50(5):528-534
Alzheimer's disease (AD) is the most common cause of cognitive impairment in older people. With the aging of society is more and more serious, AD caused great burden to patients and society. A β is a classical biomarker of AD, which has been widely used in clinical diagnosis of AD patients. Compared with positron emission tomography (PET) and single photon emission computed tomography (SPECT), near infrared fluorescence imaging has many advantages including highly sensitive, non-invasive, safety and inexpensive. Therefore, many research groups have focused on developing the molecular probes of near-infrared fluorescence (NIRF) imaging. In this article, we will review the progress of the probes of NIRF.
Alzheimer Disease
;
diagnosis
;
Amyloid beta-Peptides
;
analysis
;
Fluorescence
;
Fluorescent Dyes
;
Humans
;
Molecular Probes
;
Positron-Emission Tomography
;
Spectroscopy, Near-Infrared
;
Tomography, Emission-Computed, Single-Photon
10.Nanobody: a Novel Molecular Imaging Tool.
Chinese Journal of Medical Instrumentation 2015;39(6):423-426
Nanobodies are derived from the variable domain of the heavy-chain antibodies (HCAbs) that occur naturally in the serum of camels. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. Combined with application and clinical data of nanobody in molecular imaging in recent years, this paper introduces its application in the diagnosis of diseases and the future development as a novel molecular imaging tool.
Humans
;
Immunoglobulin Heavy Chains
;
Molecular Imaging
;
methods
;
Molecular Probes
;
Nanotechnology

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