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European Radiology
Published in: European Radiology 8/2019

Open Access 01-08-2019 | Molecular Imaging

Advances in molecular imaging of immune checkpoint targets in malignancies: current and future prospect

Authors: Yang Du, Yinhua Jin, Wei Sun, Junjie Fang, Jianjun Zheng, Jie Tian

Published in: European Radiology | Issue 8/2019

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Abstract

Objectives

This review describes the current status and progress of immune checkpoint targets for imaging of malignancies. Immune checkpoint blockade holds great potential for cancer treatment, and clinical implementation into routine is very rapidly progressing. Therefore, it is an urgent need to become familiar with the vocabulary of immunotherapy and with the evaluation of immune checkpoint and related treatments through noninvasive molecular imaging. Currently, immune target-associated imaging mainly includes PET, SPECT, optical imaging, and MRI. Each imaging method has its own inherent strengths and weaknesses in reflecting tumor morphology and physiology. PD-1, PD-L1, CTLA-4, and LAG-3 are the most commonly considered targets. In this review, the current status and progress of molecular imaging of immune checkpoint targets are discussed.

Conclusion

Molecular imaging is likely to become a major tool for monitoring immunotherapy. It can help in selecting patients who are suitable for immunotherapy, and also monitor the tumor response.

Key Points

• Immune checkpoint blockade holds great promise for the treatment of different malignant tumors.
• Molecular imaging can identify the expression of immune checkpoint targets in the tumor microenvironment at the molecular and cellular levels, and therefore helps selecting potential responders, suitable for specific immunotherapy.
• Molecular imaging can also monitor immunotherapeutic effects, and therefore participates in the evaluation of tumor response to treatment.
Literature
1.
2.
Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X (2015) Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med 21:24–33CrossRefPubMed
3.
Rizvi NA, Hellmann MD, Snyder A et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128CrossRefPubMedPubMedCentral
4.
Robert C, Long GV, Brady B et al (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320–330CrossRefPubMed
5.
Bedognetti D, Maccalli C, Bader SB, Marincola FM, Seliger B (2016) Checkpoint inhibitors and their application in breast cancer. Breast Care (Basel) 11:108–115
6.
Taube JM, Klein A, Brahmer JR et al (2014) Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 20:5064–5074CrossRefPubMedPubMedCentral
7.
James ML, Gambhir SS (2012) A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev 92:897–965CrossRefPubMed
8.
van de Watering FC, Rijpkema M, Perk L, Brinkmann U, Oyen WJ, Boerman OC (2014) Zirconium-89 labeled antibodies: a new tool for molecular imaging in cancer patients. Biomed Res Int 2014:203601
9.
Zou W, Wolchok JD, Chen L (2016) PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers and combinations. Sci Transl Med 8:328rv4CrossRefPubMedPubMedCentral
10.
Mullard A (2013) New checkpoint inhibitors ride the immunotherapy tsunami. Nat Rev Drug Discov 12:489–492CrossRefPubMed
11.
Natarajan A, Mayer AT, Xu L, Reeves RE, Gano J, Gambhir SS (2015) Novel radiotracer for immunoPET imaging of PD-1 checkpoint expression on tumor infiltrating lymphocytes. Bioconjug Chem 26:2062–2069CrossRefPubMed
12.
Anagnostou VK, Brahmer JR (2015) Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer. Clin Cancer Res 21:976CrossRefPubMed
13.
Muenst S, Soysal SD, Gao F, Obermann EC, Oertli D, Gillanders WE (2013) The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 139:667–676CrossRefPubMed
14.
Du Y, Liang X, Li Y et al (2017) Nuclear and fluorescent labeled PD-1-liposome-DOX-64Cu/IRDye800CW allows improved breast tumor targeted imaging and therapy. Mol Pharm 14:3978–3986CrossRefPubMed
15.
Chatterjee S, Lesniak WG, Gabrielson M et al (2016) A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors. Oncotarget 7:10215–10227CrossRefPubMedPubMedCentral
16.
Fay AP, Signoretti S, Callea M et al (2015) Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study. J Immunother Cancer 3:1–8CrossRef
17.
Katsuya Y, Fujita Y, Horinouchi H, Ohe Y, Watanabe S, Tsuta K (2015) Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma. Lung Cancer 88:154–159CrossRefPubMed
18.
19.
Heskamp S, Hobo W, Molkenboer-Kuenen JD et al (2015) Noninvasive imaging of tumor PD-L1 expression using radiolabeled anti-PD-L1 antibodies. Cancer Res 75:2928–2936CrossRefPubMed
20.
Spigel DR, Gettinger SN, Horn L et al (2013) Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 31:8008CrossRef
21.
Hamid O, Sosman JA, Lawrence DP et al (2013) Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). J Clin Oncol 31:9010
22.
Schmid P, Cruz C, Braiteh FS et al (2017) Atezolizumab in metastatic TNBC (mTNBC): long-term clinical outcomes and biomarker analyses. Cancer Res 77:2986–2986
23.
24.
González Trotter DE, Meng X, McQuade P et al (2017) In vivo imaging of the programmed death ligand 1 by 18F positron emission tomography. J Nucl Med 58:1852–1857CrossRefPubMed
25.
Donnelly DJ, Smith RA, Morin P et al (2018) Synthesis and biological evaluation of a novel (18)F-labeled adnectin as a PET radioligand for imaging PD-L1 expression. J Nucl Med 59:529–535CrossRefPubMed
26.
Maute RL, Gordon SR, Mayer AT et al (2015) Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc Natl Acad Sci U S A 112:E6506–E6514CrossRefPubMedPubMedCentral
27.
Mayer AT, Natarajan A, Gordon SR et al (2017) Practical immuno-PET radiotracer design considerations for human immune checkpoint imaging. J Nucl Med 58:538–546CrossRefPubMedPubMedCentral
28.
Hettich M, Braun F, Bartholomä MD, Schirmbeck R, Niedermann G (2016) High-resolution PET imaging with therapeutic antibody-based PD-1/PD-L1 checkpoint tracers. Theranostics 6:1629–1640
29.
Du Y, Liang X, Li Y et al (2017) Liposomal nanohybrid cerasomes targeted to PD-L1 enable dual-modality imaging and improve antitumor treatments. Cancer Lett 414:230–238CrossRefPubMed
30.
31.
Higashikawa K, Yagi K, Watanabe K et al (2014) 64Cu-DOTA-anti-CTLA-4 mAb enabled PET visualization of CTLA-4 on the T-cell infiltrating tumor tissues. PLoS One 9:e109866CrossRefPubMedPubMedCentral
32.
Ehlerding EB, England CG, Majewski RL et al (2017) ImmunoPET imaging of CTLA-4 expression in mouse models of non-small cell lung cancer. Mol Pharm 14:1782–1789CrossRefPubMedPubMedCentral
33.
Burugu S, Gao D, Leung S, Chia SK, Nielsen TO (2017) LAG-3+ tumor infiltrating lymphocytes in breast cancer: clinical correlates and association with PD-1/PD-L1+ tumors. Ann Oncol 28:2977–2984CrossRefPubMed
34.
Bottai G, Raschioni C, Losurdo A et al (2016) An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers. Breast Cancer Res 18:121CrossRefPubMedPubMedCentral
35.
Larimer BM, Wehrenberg-Klee E, Dubois F et al (2017) Granzyme B PET imaging as a predictive biomarker of immunotherapy response. Cancer Res 77:2318–2327CrossRefPubMedPubMedCentral
36.
Voskoboinik I, Whisstock JC, Trapani JA (2015) Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol 15:388–400CrossRefPubMed
Metadata
Title
Advances in molecular imaging of immune checkpoint targets in malignancies: current and future prospect
Authors
Yang Du
Yinhua Jin
Wei Sun
Junjie Fang
Jianjun Zheng
Jie Tian
Publication date
01-08-2019
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 8/2019
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-018-5814-3

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