Cancer Immunology, Immunotherapy

, Volume 68, Issue 5, pp 813–822 | Cite as

Monitoring of patients with metastatic melanoma treated with immune checkpoint inhibitors using PET–CT

  • Antonia Dimitrakopoulou-StraussEmail author
Focussed Research Review


Immune checkpoint inhibitors (ICI) have revolutionized therapy of metastatic melanoma. The first ICI was ipilimumab, a cytotoxic T lymphocyte-associated Ag 4 (CLTA-4) inhibitor with response rates of approximately 11% and disease control of 22%. The programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab and nivolumab, led to longer progression-free survival and overall survival rates with fewer side effects. Molecular imaging techniques, such as positron emission tomography–computed tomography (PET–CT) with 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) are in use for staging and therapy monitoring of metastatic melanoma. However, classical radiological imaging criteria such as RECIST and WHO are not appropriate for the assessment of ICI response. New immune-related criteria have been defined such as iRECIST or irRC, which refer to radiological imaging modalities. Until now only a few studies report on immunotherapy response assessment based on 18F-FDG PET–CT. The classical criteria used for therapy monitoring with 18F-FDG PET, such as the EORTC criteria, are not suitable for ICI monitoring. In this focussed review, we present different criteria proposed for ICI monitoring with 18F-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the 18F-FDG images for response assessment. Finally, the definition of 18F-FDG criteria which can be used to identify progress is crucial and discussed in the review. The recent presented PET-based immune-related criteria, the so-called PERCIMT (PET Response Evaluation Criteria for IMmunoTherapy) are presented. Furthermore, new tracers are discussed.


PET Melanoma Immunotherapy monitoring PIVAC 17 



Clinical benefit


Complete remission


Computed tomography


Cytotoxic T lymphocyte-associated Ag 4


European Organisation for Research and Treatment of Cancer


Fractal dimension


Food and Drug Administration








Gastrointestinal stromal tumor


Immune checkpoint inhibitors


Immune-related confirmed progressive disease


Immune-related adverse events


Immune-related Response Evaluation Criteria in Solid Tumors


Immune-related response criteria


Immune-related unconfirmed progressive disease


Lactate dehydrogenase




Mitogen-activated protein kinase


Myeloid-derived suppressor cells


Maximum intensity projection


Magnetic resonance imaging


Modified World Health Organisation

NK cells

Natural killer cells


No clinical benefit


Overall survival


Progressive disease


Programmed death 1 receptor


PET Response Evaluation Criteria for Immunotherapy


PET Response Criteria in Solid Tumors


Positron emission tomography


Progression-free survival


Progressive metabolic disease


Partial metabolic response


Partial remission


Response Evaluation Criteria in Solid Tumors


Region of interest


Stable disease


Stable metabolic disease


Somatostatin receptor


Standardized uptake value normalized for lean body mass


Standardized uptake value


T-cell receptor for Ag


Tumor-infiltrating lymphocyte


Vascular endothelial growth factor


World Health Organisation





The author would like to thank Jessica Hassel, MD, for her contribution to all PET–CT studies in melanoma patients.


Some of the studies mentioned in this review are based on funding upon the German Cancer Aid under the project with the title “Therapy monitoring of ipilimumab based on the quantification of 18F-FDG kinetics with 4D PET/CT (dPET–CT) in patients with melanoma (stage 4)”. The funders had no role in the preparation of this review. No additional external funding was received for this review.

Compliance with ethical standards

Conflict of interest

The author declares that she has no conflict of interest.

Ethical approval

Not applicable. This is a review and not an original paper.

Informed consent

Not applicable. This is a review and not an original paper. All patients agreed on the publication of their images.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinical Cooperation Unit Nuclear MedicineGerman Cancer Research CenterHeidelbergGermany

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