Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 5/2018

Open Access 01-10-2018 | Review Article

The Potential of In Vivo Imaging for Optimization of Molecular and Cellular Anti-cancer Immunotherapies

Authors: Gilbert O. Fruhwirth, Manfred Kneilling, I. Jolanda M. de Vries, Bettina Weigelin, Mangala Srinivas, Erik H. J. G. Aarntzen

Published in: Molecular Imaging and Biology | Issue 5/2018

Login to get access

Abstract

This review aims to emphasize the potential of in vivo imaging to optimize current and upcoming anti-cancer immunotherapies: spanning from preclinical to clinical applications. Immunotherapies are an emerging class of treatments for a variety of diseases. The agents include molecular and cellular therapeutics, which aim to treat the disease through re-education of the host immune system, often via complex mechanisms of action. In vivo imaging has the potential to contribute in several different ways: (1) as a drug development tool to improve our understanding of their complex mechanisms of action, (2) as a tool to predict efficacy, for example, to stratify patients into probable responders and likely non-responders, and (3) as a non-invasive treatment response biomarker to guide efficient immunotherapy use and to recognize early signs of potential loss of efficacy or resistance in patients. Areas where in vivo imaging is already successfully implemented in onco-immunology research will be discussed and domains where its use offers great potential will be highlighted. The focus of this article is on anti-cancer immunotherapy as it currently is the most advanced immunotherapy area. However, the described concepts can also be paralleled in other immune-mediated disorders and for conditions requiring immunotherapeutic intervention. Importantly, we introduce a new study group within the European Society of Molecular Imaging with the goal to facilitate and enhance immunotherapy development through the use of in vivo imaging.
Literature
1.
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed
2.
Mandrekar SJ, An MW, Meyers J, Grothey A et al (2014) Evaluation of alternate categorical tumor metrics and cut points for response categorization using the RECIST 1.1 data warehouse. J Clin Oncol 32:841–850CrossRefPubMedPubMedCentral
3.
Bogaerts J, Ford R, Sargent D et al (2009) Individual patient data analysis to assess modifications to the RECIST criteria. Eur J Cancer 45:248–260CrossRefPubMed
4.
Sargent DJ, Rubinstein L, Schwartz L et al (2009) Validation of novel imaging methodologies for use as cancer clinical trial end-points. Eur J Cancer 45:290–299CrossRefPubMed
5.
Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711–715CrossRefPubMed
6.
Therasse P, Eisenhauer EA, Buyse M (2006) Update in methodology and conduct of cancer clinical trials. Eur J Cancer 42:1322–1330CrossRefPubMed
7.
O’Connor JP, Aboagye EO, Adams JE et al (2017) Imaging biomarker roadmap for cancer studies. Nat Rev Clin Oncol 14:169–186CrossRefPubMed
8.
Gillies RJ, Kinahan PE, Hricak H (2016) Radiomics: images are more than pictures, they are data. Radiology 278:563–577CrossRefPubMed
9.
Seymour L, Bogaerts J, Perrone A et al (2017) iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 18:e143–e152CrossRefPubMedPubMedCentral
10.
Wolchok JD, Hoos A, O’Day S et al (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15:7412–7420CrossRefPubMed
11.
12.
13.
Nishino M, Ramaiya NH, Hatabu H, Hodi FS (2017) Monitoring immune-checkpoint blockade: response evaluation and biomarker development. Nat Rev Clin Oncol 14:655–668CrossRefPubMedPubMedCentral
14.
Postow MA, Chesney J, Pavlick AC et al (2015) Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. New Engl J Med 372:2006–2017CrossRefPubMed
15.
Robert C, Schachter J, Long GV et al (2015) Pembrolizumab versus ipilimumab in advanced melanoma. New Engl J Med 372:2521–2532CrossRefPubMed
16.
Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. New Engl J Med 363:711–723CrossRefPubMed
17.
Garon EB, Rizvi NA, Hui R et al (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. New Engl J Med 372:2018–2028CrossRefPubMed
18.
Herbst RS, Baas P, Kim DW et al (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:1540–1550CrossRefPubMed
19.
Borghaei H, Brahmer J (2016) Nivolumab in nonsquamous non-small-cell lung cancer. New Engl J Med 374:493–494PubMed
20.
Carbone DP, Reck M, Paz-Ares L et al (2017) First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. New Engl J Med 376:2415–2426CrossRefPubMed
21.
Gettinger S, Rizvi NA, Chow LQ et al (2016) Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 34:2980–2987CrossRefPubMedPubMedCentral
22.
Schadendorf D, Hodi FS, Robert C et al (2015) Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 33:1889–1894CrossRefPubMedPubMedCentral
23.
Wolchok JD, Rollin L, Larkin J (2017) Nivolumab and ipilimumab in advanced melanoma. New Engl J Med 377:2503–2504CrossRefPubMed
24.
Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New Engl J Med 366:2443–2454CrossRefPubMed
25.
Chen DS, Mellman I (2017) Elements of cancer immunity and the cancer-immune set point. Nature 541:321–330CrossRefPubMed
26.
Couzin-Frankel J (2013) Breakthrough of the year 2013. Cancer immunotherapy. Science 342:1432–1433CrossRefPubMed
27.
Brentjens RJ, Davila ML, Riviere I et al (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 5:177ra138CrossRef
28.
Kochenderfer JN, Dudley ME, Kassim SH et al (2015) Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 33:540–549CrossRefPubMed
29.
Porter DL, Hwang WT, Frey NV et al (2015) Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 7:303ra139CrossRefPubMedPubMedCentral
30.
Bach PB, Giralt SA, Saltz LB (2017) FDA approval of tisagenlecleucel: promise and complexities of a $475000 cancer drug. J Am Med Assoc 318:1861–1862CrossRef
31.
Liu Y, Chen X, Han W, Zhang Y (2017) Tisagenlecleucel, an approved anti-CD19 chimeric antigen receptor T-cell therapy for the treatment of leukemia. Drugs Today (Barc) 53:597–608CrossRef
32.
Neelapu SS, Locke FL, Bartlett NL et al (2017) Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377:2531–2544CrossRefPubMedPubMedCentral
33.
Lamers CH, Klaver Y, Gratama JW et al (2016) Treatment of metastatic renal cell carcinoma (mRCC) with CAIX CAR-engineered T-cells-a completed study overview. Biochem Soc T 44:951–959CrossRef
34.
Morgan RA, Yang JC, Kitano M et al (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 18:843–851CrossRefPubMedPubMedCentral
35.
Doss S, Garrett Z, Sutcliffe F, Stevens A (2012) NICE guidance on rituximab for first-line treatment of symptomatic stage III-IV follicular lymphoma in previously untreated patients. Lancet Oncol 13:128–130CrossRefPubMed
36.
Lovett R, George E, Adler A (2015) NICE guidance on sipuleucel-T for asymptomatic or minimally symptomatic metastatic hormone-relapsed prostate cancer. Lancet Oncol 16:369–370CrossRefPubMed
37.
Watson I, Dominguez PP, Donegan E et al (2016) NICE guidance on pembrolizumab for advanced melanoma. Lancet Oncol 17:21–22CrossRefPubMed
38.
Diaz RA, Sidhu R, Robertson J, Adam J (2013) NICE guidance on ipilimumab for previously treated advanced melanoma. Lancet Oncol 14:23–24CrossRefPubMed
39.
Hall CJ, Doss S, Robertson J, Adam J (2014) NICE guidance on ipilimumab for treating previously untreated advanced (unresectable or metastatic) melanoma. Lancet Oncol 15:1056–1057CrossRefPubMed
40.
Robert C, Thomas L, Bondarenko I et al (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. New Engl J Med 364:2517–2526CrossRefPubMed
41.
Horvat TZ, Adel NG, Dang TO et al (2015) Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol 33:3193–3198CrossRefPubMedPubMedCentral
42.
Prasad V (2018) Immunotherapy: tisagenlecleucel - the first approved CAR-T-cell therapy: implications for payers and policy makers. Nat Rev Clin Oncol 15:11–12CrossRefPubMed
43.
44.
Fridman WH, Pages F, Sautes-Fridman C, Galon J (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306CrossRefPubMed
45.
Kircher MF, Gambhir SS, Grimm J (2011) Noninvasive cell-tracking methods. Nat Rev Clin Oncol 8:677–688CrossRefPubMed
46.
Brader P, Serganova I, Blasberg RG (2013) Noninvasive molecular imaging using reporter genes. J Nucl Med 54:167–172CrossRefPubMed
47.
Rodriguez EA, Campbell RE, Lin JY et al (2017) The growing and glowing toolbox of fluorescent and photoactive proteins. Trends Biochem Sci 42:111–129CrossRefPubMed
48.
49.
Castanares MA, Mukherjee A, Chowdhury WH et al (2014) Evaluation of prostate-specific membrane antigen as an imaging reporter. J Nucl Med 55:805–811CrossRefPubMed
50.
Portulano C, Paroder-Belenitsky M, Carrasco N (2014) The Na+/I- symporter (NIS): mechanism and medical impact. Endocr Rev 35:106–149CrossRefPubMed
51.
Thunemann M, Schorg BF, Feil S et al (2017) Cre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography. Nat Commun 8:444CrossRefPubMedPubMedCentral
52.
Zeelen C, Paus C, Draper D et al (2018) In-vivo imaging of tumor-infiltrating immune cells: implications for cancer immunotherapy. Quart J Nucl Med 62:56–77
53.
Ahrens Eric TE (2013) Tracking immune cells in vivo using magnetic resonance imaging. Nat Rev Immunol 13:755–763CrossRefPubMed
54.
Weissleder R, Nahrendorf M, Pittet MJ (2014) Imaging macrophages with nanoparticles. Nat Mater 13:125–138CrossRefPubMed
55.
Bousso P (2008) T-cell activation by dendritic cells in the lymph node: lessons from the movies. Nat Rev Immunol 8:675–684CrossRefPubMed
56.
Moroz MA, Zhang H, Lee J et al (2015) Comparative analysis of T cell imaging with human nuclear reporter genes. J Nucl Med 56:1055–1060CrossRefPubMed
57.
Chacon JA, Wu RC, Sukhumalchandra P et al (2013) Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy. PLoS One 8:e60031CrossRefPubMedPubMedCentral
58.
Parente-Pereira AC, Shmeeda H, Whilding LM et al (2014) Adoptive immunotherapy of epithelial ovarian cancer with Vgamma9Vdelta2 T cells, potentiated by liposomal alendronic acid. J Immunol 193:5557–5566CrossRefPubMed
59.
Edmonds S, Volpe A, Shmeeda H et al (2016) Exploiting the metal-chelating properties of the drug cargo for in vivo positron emission tomography imaging of liposomal nanomedicines. ACS Nano 10:10294–10307CrossRefPubMedPubMedCentral
60.
Weigelin B, Bolanos E, Teijeira A et al (2015) Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb. Proc Nat Acad Sci USA 112:7551–7556CrossRefPubMedPubMedCentral
61.
Aarntzen EH, Srinivas M, Bonetto F et al (2013) Targeting of 111In-labeled dendritic cell human vaccines improved by reducing number of cells. Clin Cancer Res 19:1525–1533CrossRefPubMed
62.
de Vries IJ, Lesterhuis WJ, Barentsz JO et al (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23:1407–1413CrossRefPubMed
63.
Lesterhuis WJ, de Vries IJ, Schreibelt G et al (2011) Route of administration modulates the induction of dendritic cell vaccine-induced antigen-specific T cells in advanced melanoma patients. Clin Cancer Res 17:5725–5735CrossRefPubMed
64.
65.
Ponomarev V, Doubrovin M, Lyddane C et al (2001) Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. Neoplasia 3:480–488CrossRefPubMedPubMedCentral
66.
Lehmann S, Perera R, Grimm HP et al (2016) In vivo fluorescence imaging of the activity of CEA TCB, a novel T-cell bispecific antibody, reveals highly specific tumor targeting and fast induction of T-cell-mediated tumor killing. Clin Cancer Res 22:4417–4427CrossRefPubMed
67.
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
68.
Arlauckas SP, Garris CS, Kohler RH et al (2017) In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci Transl Med 9
69.
Grandjean CL, Montalvao F, Celli S et al (2016) Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies. Sci Rep 6:34382CrossRefPubMedPubMedCentral
70.
Park S, Shevlin E, Vedvyas Y et al (2017) Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity. Sci Rep 7:14366CrossRefPubMedPubMedCentral
71.
Linette GP, Stadtmauer EA, Maus MV et al (2013) Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122:863–871CrossRefPubMedPubMedCentral
72.
73.
74.
Daud AI, Wolchok JD, Robert C et al (2016) Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J Clin Oncol 34:4102–4109CrossRefPubMedPubMedCentral
75.
Mayer AT, Natarajan A, Gordon S et al (2016) Practical ImmunoPET radiotracer design considerations for human immune checkpoint imaging. J Nucl Med 58:538–546CrossRefPubMed
76.
Natarajan A, Mayer AT, Xu L et al (2015) Novel radiotracer for immunoPET imaging of PD-1 checkpoint expression on tumor infiltrating lymphocytes. Bioconjug Chem 26:2062–2069CrossRefPubMed
77.
Hettich M, Braun F, Bartholoma MD et al (2016) High-resolution PET imaging with therapeutic antibody-based PD-1/PD-L1 checkpoint tracers. Theranostics 6:1629–1640CrossRefPubMedPubMedCentral
78.
Wierstra P.J., Molkenboer-Kuenen J.D.M., Sandker G., Bussink J., Gotthardt M. Aarntzen E., Heskamp S., MicroSPECT/CT imaging to monitor subsequent changes in tumor PD-L1 expression after radiotherapy. In: European Molecular Imaging Meeting, 20–23 March 2018, San Sebastian, Spain, Abstractnr #0159)
79.
Tang J, Shalabi A, Hubbard-Lucey VM (2018) Comprehensive analysis of the clinical immuno-oncology landscape. Ann Oncol 29:84–91CrossRefPubMed
80.
Topalian SL, Taube JM, Anders RA, Pardoll DM (2016) Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 16:275–287CrossRefPubMedPubMedCentral
81.
Tavare R, Escuin-Ordinas H, Mok S et al (2016) An effective immuno-PET imaging method to monitor CD8-dependent responses to immunotherapy. Cancer Res 76:73–82CrossRefPubMed
82.
Freise AC, Zettlitz KA, Salazar FB, Lu X, Tavare R, Wu AM (2017) ImmunoPET imaging of murine CD4(+) T cells using anti-CD4 Cys-diabody: effects of protein dose on T cell function and imaging. Mol Imaging Biol 19:599–609CrossRefPubMedPubMedCentral
83.
Rashidian M, Ingram JR, Dougan M et al (2017) Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J Exp Med 214:2243–2255CrossRefPubMedPubMedCentral
84.
Larimer BM, Wehrenberg-Klee E, Caraballo A, Mahmood U (2016) Quantitative CD3 PET imaging predicts tumor growth response to anti-CTLA-4 therapy. J Nucl Med 57:1607–1611CrossRefPubMedPubMedCentral
85.
Kim W, Le TM, Wei L et al (2016) [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity. Proc Nal Acad Sci USA 113:4027–4032CrossRef
86.
Ribas A, Benz MR, Allen-Auerbach MS et al (2010) Imaging of CTLA4 blockade-induced cell replication with 18F-FLT PET in patients with advanced melanoma treated with tremelimumab. J Nucl Med 51:340–346CrossRefPubMed
87.
I SA, A TM, Sagiv-Barfi I, et al. (2018) Imaging activated T cells predicts response to cancer vaccines. J Clin Invest 128:2569–2580
88.
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
89.
Hartimath SV, Draghiciu O, van de Wall S et al (2017) Noninvasive monitoring of cancer therapy induced activated T cells using [imaging activated T cells predicts response to cancer vaccines F]FB-IL-2 PET imaging. Oncoimmunology 6:e1248014CrossRefPubMed
90.
Rashidian M, Keliher EJ, Bilate AM et al (2015) Noninvasive imaging of immune responses. Proc Nal Acad Sci USA 112:6146–6151CrossRef
91.
Temme S, Bonner F, Schrader J, Flogel U (2012) 19F magnetic resonance imaging of endogenous macrophages in inflammation. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4:329–343CrossRefPubMed
92.
Judenhofer MS, Wehrl HF, Newport DF et al (2008) Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat Med 14:459–465CrossRefPubMed
93.
Wehrl HF, Sauter AW, Divine MR, Pichler BJ (2015) Combined PET/MR: a technology becomes mature. J Nucl Med 56:165–168CrossRefPubMed
94.
Gong C, Yang Z, Sun Y et al (2017) A preliminary study of 18F-FES PET/CT in predicting metastatic breast cancer in patients receiving docetaxel or fulvestrant with docetaxel. Sci Rep 7:6584CrossRefPubMedPubMedCentral
95.
Peterson LM, Kurland BF, Schubert EK et al (2014) A phase 2 study of 16alpha-[18F]-fluoro-17-beta-estradiol positron emission tomography (FES-PET) as a marker of hormone sensitivity in metastatic breast cancer (MBC). Mol Imaging Biol 16:431–440CrossRefPubMed
96.
Safinia N, Vaikunthanathan T, Fraser H et al (2016) Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation. Oncotarget 7:7563–7577CrossRefPubMedPubMedCentral
97.
Afzali B, Edozie FC, Fazekasova H et al (2013) Comparison of regulatory T cells in hemodialysis patients and healthy controls: implications for cell therapy in transplantation. Clin J Am Soc Nephrol 8:1396–1405CrossRefPubMedPubMedCentral
98.
99.
Hotchkiss RS, Moldawer LL (2014) Parallels between cancer and infectious disease. New Engl J Med 371:380–383CrossRefPubMed
Metadata
Title
The Potential of In Vivo Imaging for Optimization of Molecular and Cellular Anti-cancer Immunotherapies
Authors
Gilbert O. Fruhwirth
Manfred Kneilling
I. Jolanda M. de Vries
Bettina Weigelin
Mangala Srinivas
Erik H. J. G. Aarntzen
Publication date
01-10-2018
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 5/2018
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-018-1254-3

Other articles of this Issue 5/2018

Molecular Imaging and Biology 5/2018 Go to the issue

Research Article

Tumor-Specific Zr-89 Immuno-PET Imaging in a Human Bladder Cancer Model

Research Article

Glucose Metabolism as a Pre-clinical Biomarker for the Golden Retriever Model of Duchenne Muscular Dystrophy

Research Article

Apparent Diffusion Coefficient is a Useful Biomarker for Monitoring Adipose-Derived Mesenchymal Stem Cell Therapy of Renal Ischemic-Reperfusion Injury

Review Article

Standardization of Small Animal Imaging—Current Status and Future Prospects

Research Article

Image-Based 2D Re-Projection for Attenuation Substitution in PET Neuroimaging

Review Article

On the Usage of Brain Atlases in Neuroimaging Research