Outcome Prediction and Evaluation by Imaging the Key Elements of Therapeutic Responses to Cancer Immunotherapies Using PET

Author(s): Lihong Bu*, Yanqiu Sun*, Guang Han*, Ning Tu, Jiachao Xiao, Qi Wang

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 6 , 2020

Become EABM
Become Reviewer
Call for Editor


Cancer immunotherapy (also known as immuno-oncology), a promising anti-cancer strategy by harnessing the body’s own immune system against cancer, has emerged as the “fifth therapeutic pilla” in the field of cancer treatment since surgery, chemotherapy, radiation and targeted therapy. Clinical efficacy of several immunotherapies has been demonstrated in clinical settings, however, only a small subset of patients exhibit dramatic or durable responses, with the highest reported frequency about 10-40% from single-agent PD-L1/PD-1 inhibitors, suggesting the urgent need of consistent objective response biomarkers for monitoring therapeutic response accurately, predicting therapeutic efficacy and selecting responders. Key elements of therapeutic responses to cancer immunotherapies contain the cancer cell response and the alternation of inherent immunological characteristics.

Here, we document the literature regarding imaging the key elements of therapeutic responses to cancer immunotherapies using PET. We discussed PET imaging approaches according to different response mechanisms underlying diverse immune-therapeutic categories, and also highlight the ongoing efforts to identify novel immunotherapeutic PET imaging biomarkers. In this article, we show that PET imaging of the key elements of therapeutic responses to cancer immunotherapies using PET can allow for more precise prediction, earlier therapy response monitoring, and improved management. However, all of these strategies need more preclinical study and clinical validation before further development as imaging indicators of the immune response.

Keywords: Positron emission tomography, cancer immunotherapy, therapy response, immune checkpoint blockade, adoptive T cell therapy, tumor vaccine, cytokine.

Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314(5796): 126-9.
[http://dx.doi.org/10.1126/science.1129003] [PMID: 16946036]
Robbins PF, Morgan RA, Feldman SA, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011; 29(7): 917-24.
[http://dx.doi.org/10.1200/JCO.2010.32.2537] [PMID: 21282551]
Iwai Y, Hamanishi J, Chamoto K, Honjo T. Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci 2017; 24(1): 26.
[http://dx.doi.org/10.1186/s12929-017-0329-9] [PMID: 28376884 ]
Hoos A, Janetzki S, Britten CM. Advancing the field of cancer immunotherapy: MIATA consensus guidelines become available to improve data reporting and interpretation for T-cell immune monitoring. OncoImmunology 2012; 1(9): 1457-9.
[http://dx.doi.org/10.4161/onci.22308] [PMID: 23264891]
Chen PL, Roh W, Reuben A, et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov 2016; 6(8): 827-37.
[http://dx.doi.org/10.1158/2159-8290.CD-15-1545] [PMID: 27301722 ]
Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366(10): 883-92.
[http://dx.doi.org/10.1056/NEJMoa1113205] [PMID: 22397650 ]
Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 2017; 18(3): e143-52.
[http://dx.doi.org/10.1016/S1470-2045(17)30074-8] [PMID: 28271869 ]
Kim JH, Kim BJ, Jang HJ, Kim HS. Comparison of the RECIST and EORTC PET criteria in the tumor response assessment: a pooled analysis and review. Cancer Chemother Pharmacol 2017; 80(4): 729-35.
[http://dx.doi.org/10.1007/s00280-017-3411-9] [PMID: 28780726 ]
Brindle K. New approaches for imaging tumour responses to treatment. Nat Rev Cancer 2008; 8(2): 94-107.
[http://dx.doi.org/10.1038/nrc2289] [PMID: 18202697]
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature 2017; 541(7637): 321-30.
[http://dx.doi.org/10.1038/nature21349] [PMID: 28102259]
Cheson BD, Ansell S, Schwartz L, et al. Refinement of the Lugano classification lymphoma response criteria in the era of immunomodulatory therapy. Blood 2016; 128(21): 2489-96.
[http://dx.doi.org/10.1182/blood-2016-05-718528] [PMID: 27574190 ]
Cho SY, Lipson EJ, Im HJ, et al. Prediction of response to immune checkpoint inhibitor therapy using early-time-point 18F-FDG PET/CT imaging in patients with advanced melanoma. J Nucl Med 2017; 58(9): 1421-8.
[http://dx.doi.org/10.2967/jnumed.116.188839] [PMID: 28360208]
Seith F, Forschner A, Schmidt H, et al. 18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start. Eur J Nucl Med Mol Imaging 2018; 45(1): 95-101.
[http://dx.doi.org/10.1007/s00259-017-3813-2] [PMID: 28831583]
Shields AF, Grierson JR, Dohmen BM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998; 4(11): 1334-6.
[http://dx.doi.org/10.1038/3337] [PMID: 9809561]
Nguyen NC, Yee MK, Tuchayi AM, Kirkwood JM, Tawbi H, Mountz JM. Targeted therapy and immunotherapy response assessment with F-18 fluorothymidine positron-emission tomography/magnetic resonance imaging in melanoma brain metastasis: a pilot study. Front Oncol 2018; 8: 18.
[http://dx.doi.org/10.3389/fonc.2018.00018] [PMID: 29520339]
Ribas A, Benz MR, Allen-Auerbach MS, et al. Imaging of CTLA4 blockade-induced cell replication with (18)F-FLT PET in patients with advanced melanoma treated with tremelimumab. J Nucl Med 2010; 51(3): 340-6.
[http://dx.doi.org/10.2967/jnumed.109.070946] [PMID: 20150263 ]
Nguyen LT, Ohashi PS. Clinical blockade of PD1 and LAG3--potential mechanisms of action. Nat Rev Immunol 2015; 15(1): 45-56.
[http://dx.doi.org/10.1038/nri3790] [PMID: 25534622 ]
Bordon Y. Immunotherapy: checkpoint parley. Nat Rev Cancer 2015; 15(1): 3.
[http://dx.doi.org/10.1038/nrc3880] [PMID: 25503072]
Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature 2011; 480(7378): 480-9.
[http://dx.doi.org/10.1038/nature10673] [PMID: 22193102 ]
Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer 2012; 12(4): 278-87.
[http://dx.doi.org/10.1038/nrc3236] [PMID: 22437872 ]
Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 2017; 377(14): 1345-56.
[http://dx.doi.org/10.1056/NEJMoa1709684] [PMID: 28889792 ]
Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366(26): 2455-65.
[http://dx.doi.org/10.1056/NEJMoa1200694] [PMID: 22658128 ]
Vag T, Steiger K, Rossmann A, et al. PET imaging of chemokine receptor CXCR4 in patients with primary and recurrent breast carcinoma. EJNMMI Res 2018; 8(1): 90.
[http://dx.doi.org/10.1186/s13550-018-0442-0] [PMID: 30191351 ]
Vag T, Gerngross C, Herhaus P, et al. First experience with chemokine receptor CXCR4-targeted PET imaging of patients with solid cancers. J Nucl Med 2016; 57(5): 741-6.
[http://dx.doi.org/10.2967/jnumed.115.161034] [PMID: 26769866]
Philipp-Abbrederis K, Herrmann K, Knop S, et al. In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma. EMBO Mol Med 2015; 7(4): 477-87.
[http://dx.doi.org/10.15252/emmm.201404698] [PMID: 25736399]
Herhaus P, Habringer S, Vag T, et al. Response assessment with the CXCR4-directed positron emission tomography tracer [68Ga]Pentixafor in a patient with extranodal marginal zone lymphoma of the orbital cavities. EJNMMI Res 2017; 7(1): 51.
[http://dx.doi.org/10.1186/s13550-017-0294-z] [PMID: 28577295 ]
Bensch F, van der Veen EL, Lub-de Hooge MN, et al. 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med 2018; 24(12): 1852-8.
[http://dx.doi.org/10.1038/s41591-018-0255-8] [PMID: 30478423]
Mayer AT, Natarajan A, Gordon SR, et al. Practical immuno-PET radiotracer design considerations for human immune checkpoint imaging. J Nucl Med 2017; 58(4): 538-46.
[http://dx.doi.org/10.2967/jnumed.116.177659] [PMID: 27980047]
Thurber GM, Schmidt MM, Wittrup KD. Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv Drug Deliv Rev 2008; 60(12): 1421-34.
[http://dx.doi.org/10.1016/j.addr.2008.04.012] [PMID: 18541331]
Wilks MQ, Knowles SM, Wu AM, Huang SC. Improved modeling of in vivo kinetics of slowly diffusing radiotracers for tumor imaging. J Nucl Med 2014; 55(9): 1539-44.
[http://dx.doi.org/10.2967/jnumed.114.140038] [PMID: 24994929 ]
Wittrup KD, Thurber GM, Schmidt MM, Rhoden JJ. Practical theoretic guidance for the design of tumor-targeting agents. Methods Enzymol 2012; 503: 255-68.
[http://dx.doi.org/10.1016/B978-0-12-396962-0.00010-0] [PMID: 22230572 ]
Donnelly DJ, Smith RA, Morin P, et al. Synthesis and biologic evaluation of a novel 18F-labeled adnectin as a PET radioligand for imaging PD-L1 expression. J Nucl Med 2018; 59(3): 529-35.
[http://dx.doi.org/10.2967/jnumed.117.199596] [PMID: 29025984]
Botti C, Negri DR, Seregni E, et al. Comparison of three different methods for radiolabelling human activated T lymphocytes. Eur J Nucl Med 1997; 24(5): 497-504.
[http://dx.doi.org/10.1007/BF01267680] [PMID: 9142729]
Griessinger CM, Kehlbach R, Bukala D, et al. In vivo tracking of Th1 cells by PET reveals quantitative and temporal distribution and specific homing in lymphatic tissue. J Nucl Med 2014; 55(2): 301-7.
[http://dx.doi.org/10.2967/jnumed.113.126318] [PMID: 24434289]
Keliher EJ, Yoo J, Nahrendorf M, et al. 89Zr-labeled dextran nanoparticles allow in vivo macrophage imaging. Bioconjug Chem 2011; 22(12): 2383-9.
[http://dx.doi.org/10.1021/bc200405d] [PMID: 22035047 ]
Olasz EB, Lang L, Seidel J, Green MV, Eckelman WC, Katz SI. Fluorine-18 labeled mouse bone marrow-derived dendritic cells can be detected in vivo by high resolution projection imaging. J Immunol Methods 2002; 260(1-2): 137-48.
[http://dx.doi.org/10.1016/S0022-1759(01)00528-2] [PMID: 11792384]
Keu KV, Witney TH, Yaghoubi S, et al. Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma. Sci Transl Med 2017; 9(373): 9.
[http://dx.doi.org/10.1126/scitranslmed.aag2196] [PMID: 28100832]
Yaghoubi SS, Jensen MC, Satyamurthy N, et al. Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol 2009; 6(1): 53-8.
[http://dx.doi.org/10.1038/ncponc1278] [PMID: 19015650 ]
Mall S, Yusufi N, Wagner R, et al. Immuno-PET imaging of engineered human T cells in tumors. Cancer Res 2016; 76(14): 4113-23.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2784] [PMID: 27354381]
Griessinger CM, Maurer A, Kesenheimer C, et al. 64Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET. Proc Natl Acad Sci USA 2015; 112(4): 1161-6.
[http://dx.doi.org/10.1073/pnas.1418391112] [PMID: 25587131 ]
Yusufi N, Mall S, Bianchi HO, et al. In-depth characterization of a TCR-specific tracer for sensitive detection of tumor-directed transgenic T cells by immuno-PET. Theranostics 2017; 7(9): 2402-16.
[http://dx.doi.org/10.7150/thno.17994] [PMID: 28744323]
Lee HW, Jeon YH, Hwang MH, et al. Dual reporter gene imaging for tracking macrophage migration using the human sodium iodide symporter and an enhanced firefly luciferase in a murine inflammation model. Mol Imaging Biol 2013; 15(6): 703-12.
[http://dx.doi.org/10.1007/s11307-013-0645-8] [PMID: 23677652 ]
Lee HW, Yoon SY, Singh TD, et al. Tracking of dendritic cell migration into lymph nodes using molecular imaging with sodium iodide symporter and enhanced firefly luciferase genes. Sci Rep 2015; 5: 9865.
[http://dx.doi.org/10.1038/srep09865] [PMID: 25974752]
Tavaré R, Escuin-Ordinas H, Mok S, et al. An Effective immuno-PET imaging method to monitor CD8-dependent responses to immunotherapy. Cancer Res 2016; 76(1): 73-82.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1707] [PMID: 26573799]
Tavaré R, McCracken MN, Zettlitz KA, et al. Engineered antibody fragments for immuno-PET imaging of endogenous CD8+ T cells in vivo. Proc Natl Acad Sci USA 2014; 111(3): 1108-13.
[http://dx.doi.org/10.1073/pnas.1316922111] [PMID: 24390540 ]
Rashidian M, Ingram JR, Dougan M, et al. Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J Exp Med 2017; 214(8): 2243-55.
[http://dx.doi.org/10.1084/jem.20161950] [PMID: 28666979 ]
Freise AC, Zettlitz KA, Salazar FB, Lu X, Tavaré R, Wu AM. 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 2017; 19(4): 599-609.
[http://dx.doi.org/10.1007/s11307-016-1032-z] [PMID: 27966069]
Freise AC, Zettlitz KA, Salazar FB, et al. Immuno-PET in inflammatory bowel disease: imaging CD4-positive T cells in a murine model of colitis. J Nucl Med 2018; 59(6): 980-5.
[http://dx.doi.org/10.2967/jnumed.117.199075] [PMID: 29326360]
Alam IS, Mayer AT, Sagiv-Barfi I, et al. Imaging activated T cells predicts response to cancer vaccines. J Clin Invest 2018; 128(6): 2569-80.
[http://dx.doi.org/10.1172/JCI98509] [PMID: 29596062]
Larimer BM, Wehrenberg-Klee E, Caraballo A, Mahmood U. Quantitative CD3 PET imaging predicts tumor growth response to anti-CTLA-4 therapy. J Nucl Med 2016; 57(10): 1607-11.
[http://dx.doi.org/10.2967/jnumed.116.173930] [PMID: 27230929]
Hartimath SV, Draghiciu O, van de Wall S, et al. Noninvasive monitoring of cancer therapy induced activated T cells using [18F]FB-IL-2 PET imaging. OncoImmunology 2016; 6(1)e1248014
[http://dx.doi.org/10.1080/2162402X.2016.1248014] [PMID: 28197364]
Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515(7528): 568-71.
[http://dx.doi.org/10.1038/nature13954] [PMID: 25428505]
Larimer BM, Bloch E, Nesti S, et al. The effectiveness of checkpoint inhibitor combinations and administration timing can be measured by granzyme B PET imaging. Clin Cancer Res 2019; 25(4): 1196-205.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-2407] [PMID: 30327313 ]
Larimer BM, Wehrenberg-Klee E, Dubois F, et al. Granzyme B PET imaging as a predictive biomarker of immunotherapy response. Cancer Res 2017; 77(9): 2318-27.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-3346] [PMID: 28461564]
Gibson HM, McKnight BN, Malysa A, et al. IFNγ PET imaging as a predictive tool for monitoring response to tumor immunotherapy. Cancer Res 2018; 78(19): 5706-17.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-0253] [PMID: 30115693 ]
Brickute D, Braga M, Kaliszczak MA, et al. Development and evaluation of an 18F-Radiolabeled monocyclam derivative for imaging CXCR4 expression. Mol Pharm 2019; 16(5): 2106-17.
[http://dx.doi.org/10.1021/acs.molpharmaceut.9b00069] [PMID: 30883140 ]
Amor-Coarasa A, Kelly J, Ponnala S, et al. [18F]RPS-544: A PET tracer for imaging the chemokine receptor CXCR4. Nucl Med Biol 2018; 60: 37-44.
[http://dx.doi.org/10.1016/j.nucmedbio.2018.01.004] [PMID: 29544122 ]
Hartimath SV, Khayum MA, van Waarde A, Dierckx RAJO, de Vries EFJ. N-[11C]Methyl-AMD3465 PET as a tool for in vivo measurement of chemokine receptor 4 (CXCR4) occupancy by therapeutic drugs. Mol Imaging Biol 2017; 19(4): 570-7.
[http://dx.doi.org/10.1007/s11307-016-1028-8] [PMID: 27896627 ]
Ehlerding EB, England CG, Majewski RL, et al. ImmunoPET imaging of CTLA-4 expression in mouse models of non-small cell lung cancer. Mol Pharm 2017; 14(5): 1782-9.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00056] [PMID: 28388076 ]
Jacobson O, Weiss ID, Szajek LP, et al. PET imaging of CXCR4 using copper-64 labeled peptide antagonist. Theranostics 2011; 1: 251-62.
[http://dx.doi.org/10.7150/thno/v01p0251] [PMID: 21544263 ]
González Trotter DE, Meng X, McQuade P, et al. In vivo imaging of the programmed death ligand 1 by 18F PET. J Nucl Med 2017; 58(11): 1852-7.
[http://dx.doi.org/10.2967/jnumed.117.191718] [PMID: 28588151]
Maute RL, Gordon SR, Mayer AT, et al. Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc Natl Acad Sci USA 2015; 112(47): E6506-14.
[http://dx.doi.org/10.1073/pnas.1519623112] [PMID: 26604307]
Lesniak WG, Chatterjee S, Gabrielson M, et al. PD-L1 detection in tumors using [(64)Cu]atezolizumab with PET. Bioconjug Chem 2016; 27(9): 2103-10.
[http://dx.doi.org/10.1021/acs.bioconjchem.6b00348] [PMID: 27458027 ]
Chatterjee S, Lesniak WG, Miller MS, et al. Rapid PD-L1 detection in tumors with PET using a highly specific peptide. Biochem Biophys Res Commun 2017; 483(1): 258-63.
[http://dx.doi.org/10.1016/j.bbrc.2016.12.156] [PMID: 28025143]
Ingram JR, Dougan M, Rashidian M, et al. PD-L1 is an activation-independent marker of brown adipocytes. Nat Commun 2017; 8(1): 647.
[http://dx.doi.org/10.1038/s41467-017-00799-8] [PMID: 28935898 ]
Hettich M, Braun F, Bartholomä MD, Schirmbeck R, Niedermann G. High-resolution PET imaging with therapeutic antibody-based PD-1/PD-L1 checkpoint tracers. Theranostics 2016; 6(10): 1629-40.
[http://dx.doi.org/10.7150/thno.15253] [PMID: 27446497]
England CG, Ehlerding EB, Hernandez R, et al. Preclinical pharmacokinetics and biodistribution studies of 89Zr-labeled pembrolizumab. J Nucl Med 2017; 58(1): 162-8.
[http://dx.doi.org/10.2967/jnumed.116.177857] [PMID: 27493273]
England CG, Jiang D, Ehlerding EB, et al. 89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer. Eur J Nucl Med Mol Imaging 2018; 45(1): 110-20.
[http://dx.doi.org/10.1007/s00259-017-3803-4] [PMID: 28821924]
Natarajan A, Mayer AT, Xu L, Reeves RE, Gano J, Gambhir SS. Novel radiotracer for immunoPET imaging of PD-1 checkpoint expression on tumor infiltrating lymphocytes. Bioconjug Chem 2015; 26(10): 2062-9.
[http://dx.doi.org/10.1021/acs.bioconjchem.5b00318] [PMID: 26307602]
Zanzonico P, Koehne G, Gallardo HF, et al. [131I]FIAU labeling of genetically transduced, tumor-reactive lymphocytes: cell-level dosimetry and dose-dependent toxicity. Eur J Nucl Med Mol Imaging 2006; 33(9): 988-97.
[http://dx.doi.org/10.1007/s00259-005-0057-3] [PMID: 16607546 ]
Shu CJ, Radu CG, Shelly SM, et al. Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen. Int Immunol 2009; 21(2): 155-65.
[http://dx.doi.org/10.1093/intimm/dxn133] [PMID: 19106231 ]
Dotti G, Tian M, Savoldo B, et al. Repetitive noninvasive monitoring of HSV1-tk-expressing T cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-FEAU. Mol Imaging 2009; 8(4): 230-7.
[http://dx.doi.org/10.2310/7290.2009.00022] [PMID: 19728977]
Seo JH, Jeon YH, Lee YJ, et al. Trafficking macrophage migration using reporter gene imaging with human sodium iodide symporter in animal models of inflammation. J Nucl Med 2010; 51(10): 1637-43.
[http://dx.doi.org/10.2967/jnumed.110.077891] [PMID: 20847173]
Ponomarev V, Doubrovin M, Lyddane C, et al. Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. Neoplasia 2001; 3(6): 480-8.
[http://dx.doi.org/10.1038/sj.neo.7900204] [PMID: 11774030]
Van Elssen CHMJ, Rashidian M, Vrbanac V, et al. Noninvasive imaging of human immune responses in a human xenograft model of graft-versus-host disease. J Nucl Med 2017; 58(6): 1003-8.
[http://dx.doi.org/10.2967/jnumed.116.186007] [PMID: 28209904 ]
Tavaré R, McCracken MN, Zettlitz KA, et al. Immuno-PET of murine T cell reconstitution postadoptive stem cell transplantation using anti-CD4 and anti-CD8 cys-diabodies. J Nucl Med 2015; 56(8): 1258-64.
[http://dx.doi.org/10.2967/jnumed.114.153338] [PMID: 25952734]
Olafsen T, Sirk SJ, Betting DJ, et al. ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies). Protein Eng Des Sel 2010; 23(4): 243-9.
[http://dx.doi.org/10.1093/protein/gzp081] [PMID: 20053640 ]
Zettlitz KA, Tavaré R, Knowles SM, Steward KK, Timmerman JM, Wu AM. ImmunoPET of malignant and normal B cells with 89Zr- and 124I-labeled obinutuzumab antibody fragments reveals differential CD20 internalization in vivo. Clin Cancer Res 2017; 23(23): 7242-52.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0855] [PMID: 28928164 ]
Natarajan A, Hackel BJ, Gambhir SS. A novel engineered anti-CD20 tracer enables early time PET imaging in a humanized transgenic mouse model of B-cell non-Hodgkins lymphoma. Clin Cancer Res 2013; 19(24): 6820-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0626] [PMID: 24097872 ]
Natarajan A, Habte F, Gambhir SS. Development of a novel long-lived immunoPET tracer for monitoring lymphoma therapy in a humanized transgenic mouse model. Bioconjug Chem 2012; 23(6): 1221-9.
[http://dx.doi.org/10.1021/bc300039r] [PMID: 22621257 ]
Natarajan A, Gambhir SS. Radiation dosimetry study of [(89)Zr]rituximab tracer for clinical translation of B cell NHL imaging using positron emission tomography. Mol Imaging Biol 2015; 17(4): 539-47.
[http://dx.doi.org/10.1007/s11307-014-0810-8] [PMID: 25500766 ]
Walther M, Gebhardt P, Grosse-Gehling P, et al. Implementation of 89Zr production and in vivo imaging of B-cells in mice with 89Zr-labeled anti-B-cell antibodies by small animal PET/CT. Appl Radiat Isot 2011; 69(6): 852-7.
[http://dx.doi.org/10.1016/j.apradiso.2011.02.040] [PMID: 21397511 ]
Olafsen T, Betting D, Kenanova VE, et al. Recombinant anti-CD20 antibody fragments for small-animal PET imaging of B-cell lymphomas. J Nucl Med 2009; 50(9): 1500-8.
[http://dx.doi.org/10.2967/jnumed.108.060426] [PMID: 19690034 ]
James ML, Hoehne A, Mayer AT, et al. Imaging B cells in a mouse model of multiple sclerosis using 64Cu-rituximab PET. J Nucl Med 2017; 58(11): 1845-51.
[http://dx.doi.org/10.2967/jnumed.117.189597] [PMID: 28687602 ]
Zheleznyak A, Ikotun OF, Dimitry J, Frazier WA, Lapi SE. Imaging of CD47 expression in xenograft and allograft tumor models. Mol Imaging 2013; 12(8): 12.
[http://dx.doi.org/10.2310/7290.2013.00069] [PMID: 24447619 ]
Radu CG, Shu CJ, Nair-Gill E, et al. Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2′-deoxycytidine analog. Nat Med 2008; 14(7): 783-8.
[http://dx.doi.org/10.1038/nm1724] [PMID: 18542051 ]
Kim W, Le TM, Wei L, et al. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity. Proc Natl Acad Sci USA 2016; 113(15): 4027-32.
[http://dx.doi.org/10.1073/pnas.1524212113] [PMID: 27035974]
Ronald JA, Kim BS, Gowrishankar G, et al. A PET imaging strategy to visualize activated T cells in acute graft-versus-host disease elicited by allogenic hematopoietic cell transplant. Cancer Res 2017; 77(11): 2893-902.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2953] [PMID: 28572504 ]
Namavari M, Chang YF, Kusler B, Yaghoubi S, Mitchell BS, Gambhir SS. Synthesis of 2′-deoxy-2′-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET. Mol Imaging Biol 2011; 13(5): 812-8.
[http://dx.doi.org/10.1007/s11307-010-0414-x] [PMID: 20838911 ]
Nimmagadda S, Pullambhatla M, Stone K, Green G, Bhujwalla ZM, Pomper MG. Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100 positron emission tomography. Cancer Res 2010; 70(10): 3935-44.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-4396] [PMID: 20460522 ]
Blykers A, Schoonooghe S, Xavier C, et al. PET imaging of macrophage mannose receptor-expressing macrophages in tumor stroma using 18F-radiolabeled camelid single-domain antibody fragments. J Nucl Med 2015; 56(8): 1265-71.
[http://dx.doi.org/10.2967/jnumed.115.156828] [PMID: 26069306]
Sagiv-Barfi I, Czerwinski DK, Levy S, et al. Eradication of spontaneous malignancy by local immunotherapy. Sci Transl Med 2018; 10(426): 10.
[http://dx.doi.org/10.1126/scitranslmed.aan4488] [PMID: 29386357]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 24 March, 2020
Page: [675 - 687]
Pages: 13
DOI: 10.2174/1381612825666190829150302
Price: $65

Article Metrics

PDF: 28