Molecular Imaging in Genomic Medicine


Molecular imaging is the result of advances in the fields of molecular biology and imaging technology and has become an increasingly important tool in the discovery and understanding of a wide range of pathophysiologic processes, ranging from genetic disorders to malignant conditions. The advancement in molecular pathology techniques has enabled us to study the complex genotype of disease entities and how it impacts their behaviour and natural history. Image‐guided genomic medicine utilises methodologies to integrate genomic and radiologic data to develop insights into the genotype–phenotype relationship, which in turn can guide medical decision‐making and treatment planning.

Key Concepts

  • Molecular imaging comprises the visualisation, characterisation and measurement of biological processes at the molecular and cellular levels, which can synergise with genomic medicine to enhance our understanding of disease processes.
  • Reporter gene imaging entails encoding proteins that can be rapidly and sensitively assayed as surrogate markers when fused with regulatory regions of the gene of interest as a means of indirectly monitoring molecular basis of diseases.
  • Optical imaging is based on the principle of detecting light in living organisms that reflect molecular processes; types include bioluminescence and fluorescence imaging.
  • ImmunoPET is based on combining the PET with monoclonal antibodies raised against a tumoural antigen.
  • Functional MRI uses the MRI technology to provide a means of measuring brain activity by detecting changes associated with blood flow as a phenotype that can be correlated with genotypic data.
  • Radiomics/imaging genomics leverage machine learning technology to process large data sets acquired through imaging and genomic biomarker extraction and provide valuable insights into pathophysiology and personalised disease management.
  • Gene therapeutics is another area where molecular imaging can be valuable in therapy monitoring and response assessment.

Keywords: molecular; imaging; genomic; reporter; gene; PET; MRI; optical

Figure 1. MicroPET and optical imaging: A side‐to‐side comparison of microPET (FHBG) and optical imaging (Firefly luciferase bioluminescence) in the imaging source of signal at depth below 1 cm from the exterior. Reprinted by permission from Macmillan Publishers Ltd: Nature Medicine (Massoud, T. F., Paulmurugan, R., & Gambhir, S. S. (2010). A molecularly engineered split reporter for imaging protein‐protein interactions with positron emission tomography. Nature Medicine, 16(8), 921–926), copyright (2010).
Figure 2. Optical imaging: PSA luc transgenic mice, with prostate cancer expressing luciferase. (a) Imaging of bioluminescence showing the prostate tumour signal. (b) Same mice using AngioSense 680 EX a near‐infrared labelled fluorescent macromolecule to demonstrate high tumour vascularisation. (c) Image using PET‐CT with 18F FDG (markers over the prostate tumour). Image produced by Francisca Mulero.
Figure 3. ImmunoPET: Coronal whole body PET‐CT imaging 24 h after injection of specific Ab (LEM 2/15) radiolabelled with 89Zr against Antigen MT1‐MMP in mice bearing MT1‐MMP positive pancreatic ductal adenocarcinoma (PDA) cells (red arrow) and MT1‐MMP negative breast cancer cells (yellow arrow). Observe the very high uptake in the PDA tumour showing the higher specificity of the labelled Ab (red arrow) compared with breast cancer with lower expression. Image produced by Francisca Mulero.
Figure 4. fMRI: Discovery and replication fMRI results. (a) First sample: significant clusters associated with the positive slope of polygenic coexpression index (PCI), (b) second sample: scatter plots of percentage signal change in two clusters with significant positive correlation with the PCI in the second sample. Reprinted from DRD2 co‐expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia, Bertolini et al. Translational Psychiatry (2017) 7, e1006.
Figure 5. Imaging genomics: Schema of genome‐association scanning using single‐nucleotide polymorphisms (SNPs) used for phenotypic‐genomic correlation for schizophrenia. Reprinted from DRD2 co‐expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia, Bertolini et al. Translational Psychiatry (2017) 7, e1007.


Ametamey SM, Honer M and Schubiger PA (2008) Molecular imaging with PET. Chemical Reviews 108: 1501–1516.

Bailly C, Cléry P‐F, Faivre‐Chauvet A, et al. (2017) Immuno‐PET for clinical theranostic approaches. International Journal of Molecular Sciences 18 (1): 57.

Blasberg RG (2003) Molecular imaging and cancer. Molecular Cancer Therapeutics 2: 335–343.

Chakravarty R, Shukla R, Ram R, et al. (2010) Nanoceria‐PAN composite‐based advanced sorbent material: a major step forward in the field of clinical‐grade 68Ge/68Ga generator. ACS Applied Materials & Interfaces 2: 2069–2075.

Chakravarty R, Goel S and Cai W (2014) Nanobody: the “magic bullet” for molecular imaging? Theranostics 4 (4): 386–398.

Colen RR, Vangel M, Wang J, TCGA Glioma Phenotype Research Group and Zinn PO (2014) Imaging genomic mapping of an invasive MRI phenotype predicts patient outcome and metabolic dysfunction: a TCGA glioma phenotype research group project. BMC Medical Genomics 7: 30.

Detre JA, Rao H, Wang DJJ, Chen YF and Wang Z (2012) Applications of arterial spin labeled MRI in the brain. Journal of Magnetic Resonance Imaging 35 (5): 1026–1037.

Dey D and Evans GR (2011) Suicide gene therapy by Herpes Simplex Virus‐1 Thymidine Kinase (HSV‐TK). In: You Y (ed.) Targets in Gene Therapy, Chapter 4, ISBN 978-953-307-540-2.

Divgi CR, Pandit‐Taskar N, Jungbluth AA, et al. (2007) Preoperative characterisation of clear‐cell renal carcinoma using iodine‐124‐labelled antibody chimeric G250 (124I‐cG250) and PET in patients with renal masses: a phase I trial. Lancet Oncology 8: 304–310.

Divgi CR, Uzzo RG, Gatsonis C, et al. (2013) Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial. Journal of Clinical Oncology 31: 187–194.

Gambhir SS, Barrio JR, Wu L, et al. (1998) Imaging of adenoviral‐directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir. Journal of Nuclear Medicine 39: 2003–2011.

Gambhir SS, Bauer E, Black ME, et al. (2000) A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Proceedings of the National Academy of Sciences of the United States of America 97: 2785–2790.

Gambhir SS (2002) Molecular imaging of cancer with positron emission tomography. Nature Reviews. Cancer 2: 683–693.

Hariri AR, Mattay VS, Tessitore A, et al. (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science 297: 400–403.

Hariri AR and Weinberger DR (2003) Imaging genomics. British Medical Bulletin 65 (1): 259–270.

Holliger P and Hudson PJ (2005) Engineered antibody fragments and the rise of single domains. Nature Biotechnology 23: 1126–1136.

Jauw YWS, Menke‐van der Houven van Oordt CW, Hoekstra OS, et al. (2016) Immuno‐Positron Emission Tomography with zirconium‐89‐labeled monoclonal antibodies in oncology: what can we learn from initial clinical trials? Frontiers in Pharmacology 7: 131. DOI: 10.3389/fphar.2016.00131.

Kaur S, Venktaraman G, Jain M, et al. (2012) Recent trends in antibody‐based oncologic imaging. Cancer Letters 315: 97–111.

Kiess AP, Banerjee SR, Mease RC, et al. (2015) Prostate‐specific membrane antigen as a target for cancer imaging and therapy. The Quarterly Journal of Nuclear Medicine and Molecular Imaging 59: 241–268.

Lee AD, Leow AD, Lu A, et al. (2007) 3D pattern of brain abnormalities in fragile X syndrome visualized using tensor‐based morphometry. NeuroImage 34: 924–938.

Likar Y, Dobrenkov K, Olszewska M, et al. (2008) A new acycloguanosine‐specific supermutant of Herpes Simplex Virus Type 1 Thymidine Kinase suitable for PET imaging and suicide gene therapy for potential use in patients treated with pyrimidine‐based cytotoxic drugs. Journal of Nuclear Medicine 49 (5): 713–720.

de Lucas AG, Schuhmacher AJ, Oteo M, et al. (2016) Targeting MT1‐MMP as an immunoPET‐based strategy for imaging gliomas. PLoS One 11 (7: e0158634).

Mankoff DA (2007) A definition of molecular imaging. Journal of Nuclear Medicine 48 (6: 18N, 21N).

Massoud TF, Paulmurugan R, DePritha A and Gambhir SS (2007) Reporter gene imaging of protein–protein interactions in living subjects. Current Opinion in Biotechnology 18 (1): 31–37.

McCabe KE and Wu AM (2010) Positive progress in ImmunoPET—not just a coincidence. Cancer Biotherapy & Radiopharmaceuticals 25 (3): 253–261. PMC. Web. 16 Feb. 2017.

Nguyen QH, Szeto E, Mansberg R and Mansberg V (2005) Paravertebral infection (phlegmon) demonstrated by FDG dual‐head coincidence imaging in a patient with multiple malignancies. Clinical Nuclear Medicine 30: 241–243.

Olafsen T and Wu AM (2010) Antibody vectors for imaging. Seminars in Nuclear Medicine 40: 167–181.

Ray P, De A, Min JJ, Tsien RY and Gambhir SS (2004) Imaging tri‐fusion multimodality reporter gene expression in living subjects. Cancer Research 64: 1323–1330.

Ronald J, Chuang HY, Dragulescu‐Andrasia A, Horia SH and Gambhir SS (2015) Detecting cancers through tumor‐activatable minicircles that lead to a detectable blood biomarker. PNAS 112 (10): 3068–3073; published ahead of print February 23, 2015.

Rossig C and Brenner MK (2004) Genetic modification of T lymphocytes for adoptive immunotherapy. Molecular Therapy 10: 5–18.

Shaikh F, Jacob A, Van Gestel F and Yaghoubi S (2016) Molecular imaging in genetic medicine. Cureus 8 (4): e565.

Taghva A, Kim PE, Liu CY and Apuzzo ML (2010) Molecular imaging, Part 1: apertures into the landscape of genomic medicine. World Neurosurgery 73 (4): 307–316. DOI: 10.1016/j.wneu.2010.01.020.

Tavitian B, Terrazzino S, Kuhnast B, et al. (1998) In vivo imaging of oligonucleotides with positron emission tomography. Nature Medicine 4: 467–471.

Thakor AS, Jokerst JV, Ghanouni P, et al. (2016) Clinically approved nanoparticle imaging agents. Journal of Nuclear Medicine 57: 1833–1837.

The Cancer Genome Atlas Data Portal (2012) National Cancer Institute. (accessed 15 May 2012).

The Cancer Imaging Archive (2012) National Cancer Institute. (accessed 15 May 2012).

Thompson AB and Sevick‐Muraca EM (2003) Near‐infrared fluorescence contrast‐enhanced imaging with intensified charge‐coupled device homodyne detection: measurement precision and accuracy. Journal of Biomedical Optics 8 (1): 111–120. DOI: 10.1117/1.1528205.

Thompson PM, Martin NG and Wright MJ (2010) Imaging genomics. Current Opinion in Neurology 23 (4): 368–373. DOI: 10.1097/WCO.0b013e32833b764c.

Further Reading

Celso L and de Cruz H (2014) Genetic Patterns in Neuroimaging: An Issue of Neuroimaging Clinics. Elsevier Health Sciences. ISBM 0323354637.

Gambhir S and Yaghoubi S (2010) Molecular Imaging with Reporter Genes, 1st edn. Cambridge University Press. ISBN 0521882338.

Kumar D and Eng C (2014) Genomic Medicine: Principles & Practice, 2nd edn. Oxford University Press. ISBN 019989602X.

Long N and Wong W‐T (2014) The Chemistry of Molecular imaging. Wiley. ISBN 978-1-118-09327-6.

Martí‐Bonmatí L and Alberich‐Bayarri A (2016) Imaging Biomarkers: Development and Clinical Integration. Springer. ISBN 3319435043.

Huettel S, Song A and McCarthy G (2014) Functional Magnetic Resonance Imaging, 3rd edn. Sinauer Associates, Inc. ISBN 0878936270.

Weissleder R (2010) Molecular Imaging: Principles & Practice. PMPH‐USA. ISBN 1607950057.

Zheng L and Shameem M (2015) Monoclonal Antibodies: Development, Delivery and Applications. Future Science Ltd., John Hopkins School of Medicine, USA & Merck, USA. ISBN 9781910419472.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Shaikh, Faiq A, Mulero, Francisca, and Mohiuddin, Sohaib A(Jul 2017) Molecular Imaging in Genomic Medicine. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0027219]