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OPINION

Integrating molecular nuclear imaging in clinical research to improve anticancer therapy

Nature Reviews Clinical Oncology volume 16, pages 241–255 (2019)Cite this article

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Abstract

Effective patient selection before or early during treatment is important to increasing the therapeutic benefits of anticancer treatments. This selection process is often predicated on biomarkers, predominantly biospecimen biomarkers derived from blood or tumour tissue; however, such biomarkers provide limited information about the true extent of disease or about the characteristics of different, potentially heterogeneous tumours present in an individual patient. Molecular imaging can also produce quantitative outputs; such imaging biomarkers can help to fill these knowledge gaps by providing complementary information on tumour characteristics, including heterogeneity and the microenvironment, as well as on pharmacokinetic parameters, drug–target engagement and responses to treatment. This integrative approach could therefore streamline biomarker and drug development, although a range of issues need to be overcome in order to enable a broader use of molecular imaging in clinical trials. In this Perspective article, we outline the multistage process of developing novel molecular imaging biomarkers. We discuss the challenges that have restricted the use of molecular imaging in clinical oncology research to date and outline future opportunities in this area.

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Fig. 1: Involvement of various participants in the development of molecular imaging-based biomarkers.
Fig. 2: Example of multiplexed imaging with 89Zr-bevacizumab-PET, CT, and MRI.

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Acknowledgements

The work of the authors is supported by the European Research Council (ERC) Advanced Grant 2011 OnQView (293445), Innovative Medicines Initiative 2 (IMI2) TRISTAN grant 2016 (116106), and Dutch Cancer Society IMPACT (RUG 2012–5565) and POINTING (RUG 2016–10034) grants. The authors would like to thank C. Divgi and A. Glaudemans for their valuable input into this manuscript.

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Nature Reviews Clinical Oncology thanks J. O’Connor, N. Devoogdt, and other anonymous reviewer(s) for their contribution to the peer-review of this work.

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Authors and Affiliations

  1. Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

    Elisabeth G. E. de Vries, Laura Kist de Ruijter & Sjoukje F. Oosting

  2. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

    Marjolijn N. Lub-de Hooge

  3. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

    Marjolijn N. Lub-de Hooge & Rudi A. Dierckx

  4. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

    Sjoerd G. Elias

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Correspondence to Elisabeth G. E. de Vries.

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Competing interests

E.G.E.d.V. has served on data safety monitoring boards or advisory boards for Pfizer and Sanofi and has received research funding from Amgen, Chugai, CytomX, Genentech/Roche, Nordic Nanovector, and Regeneron, with all reimbursements and funding made available to her institution (University Medical Center Groningen). The other authors declare no competing interests.

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American Board of Internal Medicine (ABIM) foundation Choosing Wisely initiative: http://www.choosingwisely.org/

American College of Radiology Accreditation: https://www.acraccreditation.org/

American College of Radiology Imaging Network (ACRIN): https://www.acrin.org/HOME.aspx

ClinicalTrials.gov database: https://clinicaltrials.gov/

EANM Research Ltd (EARL): http://earl.eanm.org/cms/website.php

ESMO-Magnitude of Clinical Benefit Scale: http://www.esmo.org/Policy/Magnitude-of-Clinical-Benefit-Scale

European Association of Nuclear Medicine (EANM): https://www.eanm.org/

European Imaging Biomarkers Alliance: http://www.eibir.org/scientific-activities/joint-initiatives/eiball/

FDA Biomarker Qualification Program: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/BiomarkerQualificationProgram/default.htm

FDA Clinical Trial Imaging Endpoint Process Standards Guidance for Industry: https://www.fda.gov/downloads/drugs/guidances/ucm268555.pdf

Innovative Medicines Initiative (IMI): http://www.imi.europa.eu/

National Biomarker Development Alliance (NBDA): http://nbdabiomarkers.org

National Biomedical Imaging Archive (NBIA): https://imaging.nci.nih.gov/ncia/login.jsf

National Cancer Institute (NCI) Cancer Imaging Program (CIP): https://imaging.cancer.gov/default.htm

NCI Clinical Trials Working Group (CTWG) Biomarker Study Evaluation Guidelines: https://www.cancer.gov/about-nci/organization/ccct/funding/biqsfp/2017-biomarker-study-eval-guide.pdf

NCI Quantitative Imaging Network (QIN): https://imaging.cancer.gov/programs_resources/specialized_initiatives/qin/about/default.htm

Quantitative Imaging Biomarkers Alliance (QIBA): https://www.rsna.org/QIBA/

Quantitative Imaging Data Warehouse (QIDW): https://www.rsna.org/QIDW/

RECIST criteria: http://recist.eortc.org/

Society of Nuclear Medicine and Molecular Imaging (SNMMI): http://www.snmmi.org/Research/ClinicalTrialsNetwork.aspx?ItemNumber=6831

The Cancer Imaging Archive (TCIA): http://www.cancerimagingarchive.net

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de Vries, E.G.E., Kist de Ruijter, L., Lub-de Hooge, M.N. et al. Integrating molecular nuclear imaging in clinical research to improve anticancer therapy. Nat Rev Clin Oncol 16, 241–255 (2019). https://doi.org/10.1038/s41571-018-0123-y

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