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Fulltext Molecular Imaging - a way forward in translating disease behaviour in an era of personalized medicine

Fathinul Fikri AS

J Int Med Res, 2018 Feb;46(2):652-653.
PMID: 28718732 DOI: 10.1177/0300060517719211
Matched MeSH terms: Molecular Imaging*
Fulltext Generation of peptides using phage display technology for cancer diagnosis and molecular imaging

Pung HS, Tye GJ, Leow CH, Ng WK, Lai NS

Mol Biol Rep, 2023 May;50(5):4653-4664.
PMID: 37014570 DOI: 10.1007/s11033-023-08380-x

Cancer is one of the leading causes of mortality worldwide; nearly 10 million people died from it in 2020. The high mortality rate results from the lack of effective screening approaches where early detection cannot be achieved, reducing the chance of early intervention to prevent cancer development. Non-invasive and deep-tissue imaging is useful in cancer diagnosis, contributing to a visual presentation of anatomy and physiology in a rapid and safe manner. Its sensitivity and specificity can be enhanced with the application of targeting ligands with the conjugation of imaging probes. Phage display is a powerful technology to identify antibody- or peptide-based ligands with effective binding specificity against their target receptor. Tumour-targeting peptides exhibit promising results in molecular imaging, but the application is limited to animals only. Modern nanotechnology facilitates the combination of peptides with various nanoparticles due to their superior characteristics, rendering novel strategies in designing more potent imaging probes for cancer diagnosis and targeting therapy. In the end, a myriad of peptide candidates that aimed for different cancers diagnosis and imaging in various forms of research were reviewed.

Matched MeSH terms: Molecular Imaging
Fulltext Molecular imaging: spawning a new melting-pot for biomedical imaging

Abdullah B

Biomed Imaging Interv J, 2006 Oct;2(4):e28.
PMID: 21614327 MyJurnal DOI: 10.2349/biij.2.4.e28

Predicting the future is a dangerous undertaking at best, and not meant for the faint-hearted. However, viewing the advances in molecular medicine, genomics and proteomics, it is easy to comprehend those who believe that molecular imaging methods will open up new vistas for medical imaging. The knock on effect will impact our capacity to diagnose and treat diseases. Anatomically detectable abnormalities, which have historically been the basis of the practice of radiology, will soon be replaced by molecular imaging methods that will reflect the under expression or over expression of certain genes which occur in almost every disease. Molecular imaging can then be resorted to so that early diagnosis and characterisation of disease can offer improved specificity. Given the growing importance of molecular medicine, imagers will find it profitable to educate themselves on molecular targeting, molecular therapeutics and the role of imaging in both areas.

Matched MeSH terms: Molecular Imaging
Cd(2+) Triggered the FRET "ON": A New Molecular Switch for the Ratiometric Detection of Cd(2+) with Live-Cell Imaging and Bound X-ray Structure

Aich K, Goswami S, Das S, Mukhopadhyay CD, Quah CK, Fun HK

Inorg Chem, 2015 Aug 3;54(15):7309-15.
PMID: 26192906 DOI: 10.1021/acs.inorgchem.5b00784

On the basis of the Förster resonance energy transfer mechanism between rhodamine and quinoline-benzothiazole conjugated dyad, a new colorimetric as well as fluorescence ratiometric probe was synthesized for the selective detection of Cd(2+). The complex formation of the probe with Cd(2+) was confirmed through Cd(2+)-bound single-crystal structure. Capability of the probe as imaging agent to detect the cellular uptake of Cd(2+) was demonstrated here using living RAW cells.

Matched MeSH terms: Molecular Imaging/methods*
Fulltext Determination of an optimally sensitive and specific chemical exchange saturation transfer MRI quantification metric in relevant biological phantoms

Ray KJ, Larkin JR, Tee YK, Khrapitchev AA, Karunanithy G, Barber M, et al.

NMR Biomed, 2016 11;29(11):1624-1633.
PMID: 27686882 DOI: 10.1002/nbm.3614

The purpose of this study was to develop realistic phantom models of the intracellular environment of metastatic breast tumour and naïve brain, and using these models determine an analysis metric for quantification of CEST MRI data that is sensitive to only labile proton exchange rate and concentration. The ability of the optimal metric to quantify pH differences in the phantoms was also evaluated. Novel phantom models were produced, by adding perchloric acid extracts of either metastatic mouse breast carcinoma cells or healthy mouse brain to bovine serum albumin. The phantom model was validated using 1 H NMR spectroscopy, then utilized to determine the sensitivity of CEST MRI to changes in pH, labile proton concentration, T1 time and T2 time; six different CEST MRI analysis metrics (MTRasym , APT*, MTRRex , AREX and CESTR* with and without T1 /T2 compensation) were compared. The new phantom models were highly representative of the in vivo intracellular environment of both tumour and brain tissue. Of the analysis methods compared, CESTR* with T1 and T2 time compensation was optimally specific to changes in the CEST effect (i.e. minimal contamination from T1 or T2 variation). In phantoms with identical protein concentrations, pH differences between phantoms could be quantified with a mean accuracy of 0.6 pH units. We propose that CESTR* with T1 and T2 time compensation is the optimal analysis method for these phantoms. Analysis of CEST MRI data with T1 /T2 time compensated CESTR* is reproducible between phantoms, and its application in vivo may resolve the intracellular alkalosis associated with breast cancer brain metastases without the need for exogenous contrast agents.

Matched MeSH terms: Molecular Imaging/instrumentation*; Molecular Imaging/methods
Label-free methods of reporting biomolecular interactions by optical biosensors

Citartan M, Gopinath SC, Tominaga J, Tang TH

Analyst, 2013 Jul 7;138(13):3576-92.
PMID: 23646346 DOI: 10.1039/c3an36828a

Reporting biomolecular interactions has become part and parcel of many applications of science towards an in-depth understanding of disease and gene regulation. Apart from that, in diagnostic applications where biomolecules (antibodies and aptamers) are vastly applied, meticulous monitoring of biomolecular interaction is vital for clear-cut diagnosis. Several currently available methods of analyzing the interaction of the ligands with the appropriate analytes are aided by labeling using fluorescence or luminescence techniques. However, labeling is cumbersome and can occupy important binding sites of interactive molecules to be labeled, which may interfere with the conformational changes of the molecules and increase non-specificity. Optical-based sensing can provide an alternative way as a label-free procedure for monitoring biomolecular interactions. Optical sensors affiliated with different operating principles, including surface plasmon changes, scattering and interferometry, can impart a huge impact for in-house and point-of-care applications. This optical-based biosensing permits real-time monitoring, obviating the use of hazardous labeling molecules such as radioactive tags. Herein, label-free ways of reporting biomolecular interactions by various optical biosensors were gleaned.

Matched MeSH terms: Molecular Imaging
Fulltext Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of macrophages in large vessel vasculitis: Current status and future prospects

Jiemy WF, Heeringa P, Kamps JAAM, van der Laken CJ, Slart RHJA, Brouwer E

Autoimmun Rev, 2018 Jul;17(7):715-726.
PMID: 29729443 DOI: 10.1016/j.autrev.2018.02.006

Macrophages are key players in the pathogenesis of large-vessel vasculitis (LVV) and may serve as a target for diagnostic imaging of LVV. The radiotracer, 18F-FDG has proven to be useful in the diagnosis of giant cell arteritis (GCA), a form of LVV. Although uptake of 18F-FDG is high in activated macrophages, it is not a specific radiotracer as its uptake is high in any proliferating cell and other activated immune cells resulting in high non-specific background radioactivity especially in aging and atherosclerotic vessels which dramatically lowers the diagnostic accuracy. Evidence also exists that the sensitivity of 18F-FDG PET drops in patients upon glucocorticoid treatment. Therefore, there is a clinical need for more specific radiotracers in imaging GCA to improve diagnostic accuracy. Numerous clinically established and newly developed macrophage targeted radiotracers for oncological and inflammatory diseases can potentially be utilized for LVV imaging. These tracers are more target specific and therefore may provide lower background radioactivity, higher diagnostic accuracy and the ability to assess treatment effectiveness. However, current knowledge regarding macrophage subsets in LVV lesions is limited. Further understanding regarding macrophage subsets in vasculitis lesion is needed for better selection of tracers and new targets for tracer development. This review summarizes the development of macrophage targeted tracers in the last decade and the potential application of macrophage targeted tracers currently used in other inflammatory diseases in imaging LVV.

Matched MeSH terms: Molecular Imaging
Fulltext Systematic Review on the Accuracy of Positron Emission Tomography/Computed Tomography and Positron Emission Tomography/Magnetic Resonance Imaging in the Management of Ovarian Cancer: Is Functional Information Really Needed?

Suppiah S, Chang WL, Hassan HA, Kaewput C, Asri AAA, Saad FFA, et al.

World J Nucl Med, 2017 Jul-Sep;16(3):176-185.
PMID: 28670174 DOI: 10.4103/wjnm.WJNM_31_17

Ovarian cancer (OC) often presents at an advanced stage with frequent relapses despite optimal treatment; thus, accurate staging and restaging are required for improving treatment outcomes and prognostication. Conventionally, staging of OC is performed using contrast-enhanced computed tomography (CT). Nevertheless, recent advances in the field of hybrid imaging have made positron emission tomography/CT (PET/CT) and PET/magnetic resonance imaging (PET/MRI) as emerging potential noninvasive imaging tools for improved management of OC. Several studies have championed the role of PET/CT for the detection of recurrence and prognostication of OC. We provide a systematic review and meta-analysis of the latest publications regarding the role of molecular imaging in the management of OC. We retrieved 57 original research articles with one article having overlap in both diagnosis and staging; 10 articles (734 patients) regarding the role of PET/CT in diagnosis of OC; 12 articles (604 patients) regarding staging of OC; 22 studies (1429 patients) for detection of recurrence; and 13 articles for prognostication and assessment of treatment response. We calculated pooled sensitivity and specificity of PET/CT performance in various aspects of imaging of OC. We also discussed the emerging role of PET/MRI in the management of OC. We aim to give the readers and objective overview on the role of molecular imaging in the management of OC.

Matched MeSH terms: Molecular Imaging
Fulltext 18F[AlF]-radiolabelled Peptides on the Automated Synthesis Platform: Translating the Laboratory Bench Work to Bedside

Hassan H, Razak HRA, Saad FFA, Kumar V

Malays J Med Sci, 2019 Jul;26(4):122-126.
PMID: 31496901 MyJurnal DOI: 10.21315/mjms2019.26.4.14

Using radiolabelled peptides that bind, with high affinity and specificity, to receptors on tumour cells is one of the most promising fields in modern molecular imaging and targeted radionuclide therapy (1). In the emergence of molecular imaging and nuclear medicine diagnosis and therapy, albeit theranostic, radiolabelled peptides have become vital tools for in vivo visualisation and monitoring physiological and biochemical processes on molecular and cellular levels (2). This approach may benefit patients in the era of personalised medicine.

Matched MeSH terms: Molecular Imaging
Fulltext Standardized Uptake Value from Semiquantitative Bone Single-Photon Emission Computed Tomography/Computed Tomography in Normal Thoracic and Lumbar Vertebrae of Breast Cancer Patients

Rohani MFM, Yonan SNM, Tagiling N, Zainon WMNW, Udin Y, Nawi NM

Asian Spine J, 2020 Oct;14(5):629-638.
PMID: 32213791 DOI: 10.31616/asj.2019.0308

STUDY DESIGN: Retrospective study.
PURPOSE: This study aims to semiquantitatively evaluate the standardized uptake value (SUV) of 99mTc-methylene diphosphonate (MDP) radionuclide tracer in the normal vertebrae of breast cancer patients using an integrated single-photon emission computed tomography (SPECT)/computed tomography (CT) scanner.
OVERVIEW OF LITERATURE: Molecular imaging techniques using gamma cameras and stand-alone SPECT have traditionally been utilized to evaluate metastatic bone diseases. However, these methods lack quantitative analysis capabilities, impeding accurate uptake characterization.
METHODS: A total of 30 randomly selected female breast cancer patients were enrolled in this study. The SUV mean (SUVmean) and SUV maximum (SUVmax) values for 286 normal vertebrae at the thoracic and lumbar levels were calculated based on the patients' body weight (BW), body surface area (BSA), and lean body mass (LBM). Additionally, 106 degenerative joint disease (DJD) lesions of the spine were also characterized, and both their BW SUVmean and SUVmax values were obtained. A receiver operating characteristic (ROC) curve analysis was then performed to determine the cutoff value of SUV for differentiating DJD from normal vertebrae.
RESULTS: The mean±standard deviations for the SUVmean and SUVmax in the normal vertebrae displayed a relatively wide variability: 3.92±0.27 and 6.51±0.72 for BW, 1.05±0.07 and 1.75±0.17 for BSA, and 2.70±0.19 and 4.50±0.44 for LBM, respectively. Generally, the SUVmean had a lower coefficient of variation than the SUVmax. For DJD, the mean±standard deviation for the BW SUVmean and SUVmax was 5.26±3.24 and 7.50±4.34, respectively. Based on the ROC curve, no optimal cutoff value was found to differentiate DJD from normal vertebrae.
CONCLUSIONS: In this study, the SUV of 99mTc-MDP was successfully determined using SPECT/CT. This research provides an approach that could potentially aid in the clinical quantification of radionuclide uptake in normal vertebrae for the management of breast cancer patients.

Matched MeSH terms: Molecular Imaging
In vitro Study of SPIONs-C595 as Molecular Imaging Probe for Specific Breast Cancer (MCF-7) Cells Detection

Moradi Khaniabadi P, Shahbazi-Gahrouei D, Malik Shah Abdul Majid A, Suhaimi Jaafar M, Moradi Khaniabadi B, Shahbazi-Gahrouei S

Iran Biomed J, 2017 11;21(6):360-8.
PMID: 28601058

Background: Magnetic resonance imaging (MRI) plays an essential role in molecular imaging by delivering the contrast agent into targeted cancer cells. The aim of this study was to evaluate the C595 monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (SPIONs-C595) for the detection of breast cancer cell (MCF-7).
Methods: The conjugation of monoclonal antibody and nanoparticles was confirmed using X-ray diffraction, transmission electron microscopy, and photon correlation spectroscopy. The selectivity of the nanoprobe for breast cancer cells (MCF-7) was obtained by Prussian blue, atomic emission spectroscopy, and
MRI relaxometry.
Results: The in vitro MRI showed that T2 relaxation time will be reduced 76% when using T2-weighed magnetic resonance images compared to the control group (untreated cells) at the dose of 200 μg
Fe/ml, as the optimum dose. In addition, the results showed the high uptake of nanoprobe into MCF-7
cancer cells.
Conclusion: The SPIONs-C595 nanoprobe has potential for the detection of specific breast cancer.

Matched MeSH terms: Molecular Imaging
MALDI Mass Spectrometry Imaging of Early- and Late-Stage Serous Ovarian Cancer Tissue Reveals Stage-Specific N-Glycans

Briggs MT, Condina MR, Ho YY, Everest-Dass AV, Mittal P, Kaur G, et al.

Proteomics, 2019 11;19(21-22):e1800482.
PMID: 31364262 DOI: 10.1002/pmic.201800482

Epithelial ovarian cancer is one of the most fatal gynecological malignancies in adult women. As studies on protein N-glycosylation have extensively reported aberrant patterns in the ovarian cancer tumor microenvironment, obtaining spatial information will uncover tumor-specific N-glycan alterations in ovarian cancer development and progression. matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is employed to investigate N-glycan distribution on formalin-fixed paraffin-embedded ovarian cancer tissue sections from early- and late-stage patients. Tumor-specific N-glycans are identified and structurally characterized by porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry (PGC-LC-ESI-MS/MS), and then assigned to high-resolution images obtained from MALDI-MSI. Spatial distribution of 14 N-glycans is obtained by MALDI-MSI and 42 N-glycans (including structural and compositional isomers) identified and structurally characterized by LC-MS. The spatial distribution of oligomannose, complex neutral, bisecting, and sialylated N-glycan families are localized to the tumor regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycan diagnostic markers that emerge include the oligomannose structure, (Hex)6 + (Man)3 (GlcNAc)2 , and the complex neutral structure, (Hex)2 (HexNAc)2 (Deoxyhexose)1 + (Man)3 (GlcNAc)2 . The distribution of these markers is evaluated using a tissue microarray of early- and late-stage patients.

Matched MeSH terms: Molecular Imaging

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