Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-11-2020 | Solid Tumor | Original Article

Development and characterization of CD54-targeted immunoPET imaging in solid tumors

Authors: Weijun Wei, Dawei Jiang, Hye Jin Lee, Miao Li, Christopher J. Kutyreff, Jonathan W. Engle, Jianjun Liu, Weibo Cai

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2020

Abstract

Purpose

Intercellular adhesion molecule-1 (ICAM-1, CD54) is an emerging therapeutic target for a variety of solid tumors including melanoma and anaplastic thyroid cancer (ATC). This study aims to develop an ICAM-1-targeted immuno-positron emission tomography (immunoPET) imaging strategy and assess its diagnostic value in melanoma and ATC models.

Methods

Flow cytometry was used to screen ICAM-1-positive melanoma and ATC cell lines. Melanoma and ATC models were established using A375 cell line and THJ-16T cell line, respectively. An ICAM-1-specific monoclonal antibody (R6-5-D6) and a nonspecific human IgG were radiolabeled with ⁶⁴Cu and the diagnostic efficacies were interrogated in tumor-bearing mouse models. Biodistribution and fluorescent imaging studies were performed to confirm the specificity of the ICAM-1-targeted imaging probes.

Results

ICAM-1 was strongly expressed on melanoma and advanced thyroid cancer cell lines. ⁶⁴Cu-NOTA-ICAM-1 immunoPET imaging efficiently delineated A375 melanomas with a peak tumor uptake of 21.28 ± 6.56 %ID/g (n = 5), significantly higher than that of ⁶⁴Cu-NOTA-IgG (10.63 ± 2.58 %ID/g, n = 3). Moreover, immunoPET imaging with ⁶⁴Cu-NOTA-ICAM-1 efficiently visualized subcutaneous and orthotopic ATCs with high clarity and contrast. Fluorescent imaging with IRDye 800CW-ICAM-1 also visualized orthotopic ATCs and the tumor uptake could be blocked by the ICAM-1 parental antibody R6-5-D6, indicating the high specificity of the developed probe. Finally, blocking with the human IgG prolonged the circulation of the ⁶⁴Cu-NOTA-ICAM-1 in R2G2 mice without compromising the tumor uptake.

Conclusion

ICAM-1-targeted immunoPET imaging could characterize ICAM-1 expression in melanoma and ATC, which holds promise for optimizing ICAM-1-targeted therapies in the future.

Available only for authorised users

Reina M, Espel E. Role of LFA-1 and ICAM-1 in cancer. Cancers (Basel). 2017;9. https://doi.org/10.3390/cancers9110153.

Yang L, Froio RM, Sciuto TE, Dvorak AM, Alon R, Luscinskas FW. ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow. Blood. 2005;106:584–92. https://doi.org/10.1182/blood-2004-12-4942.CrossRefPubMedPubMedCentral

Hayes SH, Seigel GM. Immunoreactivity of ICAM-1 in human tumors, metastases and normal tissues. Int J Clin Exp Pathol. 2009;2:553–60.PubMedPubMedCentral

Hamai A, Meslin F, Benlalam H, Jalil A, Mehrpour M, Faure F, et al. ICAM-1 has a critical role in the regulation of metastatic melanoma tumor susceptibility to CTL lysis by interfering with PI3K/AKT pathway. Cancer Res. 2008;68:9854–64. https://doi.org/10.1158/0008-5472.CAN-08-0719.CrossRefPubMed

Zhang P, Goodrich C, Fu C, Dong C. Melanoma upregulates ICAM-1 expression on endothelial cells through engagement of tumor CD44 with endothelial E-selectin and activation of a PKCalpha-p38-SP-1 pathway. FASEB J. 2014;28:4591–609. https://doi.org/10.1096/fj.11-202747.CrossRefPubMedPubMedCentral

Galore-Haskel G, Baruch EN, Berg AL, Barshack I, Zilinsky I, Avivi C, et al. Histopathological expression analysis of intercellular adhesion molecule 1 (ICAM-1) along development and progression of human melanoma. Oncotarget. 2017;8:99580–6. https://doi.org/10.18632/oncotarget.20884.CrossRefPubMedPubMedCentral

Buitrago D, Keutgen XM, Crowley M, Filicori F, Aldailami H, Hoda R, et al. Intercellular adhesion molecule-1 (ICAM-1) is upregulated in aggressive papillary thyroid carcinoma. Ann Surg Oncol. 2012;19:973–80. https://doi.org/10.1245/s10434-011-2029-0.CrossRefPubMed

Min IM, Shevlin E, Vedvyas Y, Zaman M, Wyrwas B, Scognamiglio T, et al. CAR T therapy targeting ICAM-1 eliminates advanced human thyroid tumors. Clin Cancer Res. 2017;23:7569–83. https://doi.org/10.1158/1078-0432.CCR-17-2008.CrossRefPubMedPubMedCentral

Vedvyas Y, McCloskey JE, Yang Y, Min IM, Fahey TJ, Zarnegar R, et al. Manufacturing and preclinical validation of CAR T cells targeting ICAM-1 for advanced thyroid cancer therapy. Sci Rep. 2019;9:10634. https://doi.org/10.1038/s41598-019-46938-7.CrossRefPubMedPubMedCentral

10.

James ML, Gambhir SS. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012;92:897–965. https://doi.org/10.1152/physrev.00049.2010.CrossRefPubMed

11.

Guo P, Huang J, Wang L, Jia D, Yang J, Dillon DA, et al. ICAM-1 as a molecular target for triple negative breast cancer. Proc Natl Acad Sci U S A. 2014;111:14710–5. https://doi.org/10.1073/pnas.1408556111.CrossRefPubMedPubMedCentral

12.

Bensch F, Smeenk MM, van Es SC, de Jong JR, Schroder CP, Oosting SF, et al. Comparative biodistribution analysis across four different (89)Zr-monoclonal antibody tracers-the first step towards an imaging warehouse. Theranostics. 2018;8:4295–304. https://doi.org/10.7150/thno.26370.CrossRefPubMedPubMedCentral

13.

Bensch F, Brouwers AH, Lub-de Hooge MN, de Jong JR, van der Vegt B, Sleijfer S, et al. (89)Zr-trastuzumab PET supports clinical decision making in breast cancer patients, when HER2 status cannot be determined by standard work up. Eur J Nucl Med Mol Imaging. 2018;45:2300–6. https://doi.org/10.1007/s00259-018-4099-8.CrossRefPubMedPubMedCentral

14.

Ulaner GA, Lyashchenko SK, Riedl C, Ruan S, Zanzonico PB, Lake D, et al. First-in-human human epidermal growth factor receptor 2-targeted imaging using (89)Zr-Pertuzumab PET/CT: dosimetry and clinical application in patients with breast cancer. J Nucl Med. 2018;59:900–6. https://doi.org/10.2967/jnumed.117.202010.CrossRefPubMedPubMedCentral

15.

Wei W, Ni D, Ehlerding EB, Luo Q-Y, Cai W. PET imaging of receptor tyrosine kinases in cancer. Mol Cancer Ther. 2018;17:1625–36. https://doi.org/10.1158/1535-7163.mct-18-0087.CrossRefPubMedPubMedCentral

16.

Lamberts LE, Menke-van der Houven van Oordt CW, ter Weele EJ, Bensch F, Smeenk MM, Voortman J, et al. ImmunoPET with anti-mesothelin antibody in patients with pancreatic and ovarian cancer before anti-mesothelin antibody-drug conjugate treatment. Clin Cancer Res. 2016;22:1642–52. https://doi.org/10.1158/1078-0432.CCR-15-1272.CrossRefPubMed

17.

Wei W, Jiang D, Ehlerding EB, Luo Q, Cai W. Noninvasive PET imaging of T cells. Trends Cancer. 2018;4:359–73. https://doi.org/10.1016/j.trecan.2018.03.009.CrossRefPubMedPubMedCentral

18.

Cai W, Rao J, Gambhir SS, Chen X. How molecular imaging is speeding up antiangiogenic drug development. Mol Cancer Ther. 2006;5:2624–33. https://doi.org/10.1158/1535-7163.MCT-06-0395.CrossRefPubMed

19.

Wei W, Jiang D, Ehlerding EB, Barnhart TE, Yang Y, Engle JW, et al. CD146-targeted multimodal image-guided photoimmunotherapy of melanoma. Adv Sci (Weinh). 2019;6:1801237. https://doi.org/10.1002/advs.201801237.CrossRef

20.

Wei W, Jiang D, Rosenkrans ZT, Barnhart TE, Engle JW, Luo Q, et al. HER2-targeted multimodal imaging of anaplastic thyroid cancer. Am J Cancer Res. 2019;9:2413–27.PubMedPubMedCentral

21.

Nucera C, Nehs MA, Mekel M, Zhang X, Hodin R, Lawler J, et al. A novel orthotopic mouse model of human anaplastic thyroid carcinoma. Thyroid. 2009;19:1077–84. https://doi.org/10.1089/thy.2009.0055.CrossRefPubMedPubMedCentral

22.

Jin Y, Liu M, Sa R, Fu H, Cheng L, Chen L. Mouse models of thyroid cancer: bridging pathogenesis and novel therapeutics. Cancer Lett. 2020;469:35–53. https://doi.org/10.1016/j.canlet.2019.09.017.CrossRefPubMed

23.

Yang Y, Hernandez R, Rao J, Yin L, Qu Y, Wu J, et al. Targeting CD146 with a 64Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas. Proc Natl Acad Sci U S A. 2015;112:E6525–34. https://doi.org/10.1073/pnas.1502648112.CrossRefPubMedPubMedCentral

24.

Cohen R, Vugts DJ, Stigter-van Walsum M, Visser GW, van Dongen GA. Inert coupling of IRDye800CW and zirconium-89 to monoclonal antibodies for single- or dual-mode fluorescence and PET imaging. Nat Protoc. 2013;8:1010–8. https://doi.org/10.1038/nprot.2013.054.CrossRefPubMed

25.

Wei W, Ehlerding EB, Lan X, Luo Q, Cai W. PET and SPECT imaging of melanoma: the state of the art. Eur J Nucl Med Mol Imaging. 2018;45:132–50. https://doi.org/10.1007/s00259-017-3839-5.CrossRefPubMed

26.

Sharma SK, Chow A, Monette S, Vivier D, Pourat J, Edwards KJ, et al. Fc-mediated anomalous biodistribution of therapeutic antibodies in immunodeficient mouse models. Cancer Res. 2018;78:1820–32. https://doi.org/10.1158/0008-5472.Can-17-1958.CrossRefPubMedPubMedCentral

27.

Pereira PMR, Abma L, Henry KE, Lewis JS. Imaging of human epidermal growth factor receptors for patient selection and response monitoring - from PET imaging and beyond. Cancer Lett. 2018;419:139–51. https://doi.org/10.1016/j.canlet.2018.01.052.CrossRefPubMed

28.

Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol. 2004;22:3608–17. https://doi.org/10.1200/JCO.2004.01.175.CrossRefPubMed

29.

Pandit-Taskar N, O'Donoghue JA, Beylergil V, Lyashchenko S, Ruan S, Solomon SB, et al. (8)(9)Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:2093–105. https://doi.org/10.1007/s00259-014-2830-7.CrossRefPubMedPubMedCentral

30.

Moek KL, Giesen D, Kok IC, de Groot DJA, Jalving M, Fehrmann RSN, et al. Theranostics using antibodies and antibody-related therapeutics. J Nucl Med. 2017;58:83S–90S. https://doi.org/10.2967/jnumed.116.186940.CrossRefPubMed

31.

Burvenich IJG, Parakh S, Parslow AC, Lee ST, Gan HK, Scott AM. Receptor occupancy imaging studies in oncology drug development. AAPS J. 2018;20:43. https://doi.org/10.1208/s12248-018-0203-z.CrossRefPubMed

32.

Lamberts LE, Williams SP, Terwisscha van Scheltinga AG, Lub-de Hooge MN, Schroder CP, Gietema JA, et al. Antibody positron emission tomography imaging in anticancer drug development. J Clin Oncol. 2015;33:1491–504. https://doi.org/10.1200/JCO.2014.57.8278.CrossRefPubMed

33.

Wu X, Guo R, Wang Y, Cunningham PN. The role of ICAM-1 in endotoxin-induced acute renal failure. Am J Physiol Renal Physiol. 2007;293:F1262–71. https://doi.org/10.1152/ajprenal.00445.2006.CrossRefPubMed

34.

Mar D, Gharib SA, Zager RA, Johnson A, Denisenko O, Bomsztyk K. Heterogeneity of epigenetic changes at ischemia/reperfusion- and endotoxin-induced acute kidney injury genes. Kidney Int. 2015;88:734–44. https://doi.org/10.1038/ki.2015.164.CrossRefPubMedPubMedCentral

35.

Zumwalde NA, Domae E, Mescher MF, Shimizu Y. ICAM-1-dependent homotypic aggregates regulate CD8 T cell effector function and differentiation during T cell activation. J Immunol. 2013;191:3681–93. https://doi.org/10.4049/jimmunol.1201954.CrossRefPubMed

36.

Hailemichael Y, Woods A, Fu T, He Q, Nielsen MC, Hasan F, et al. Cancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy. J Clin Invest. 2018;128:1338–54. https://doi.org/10.1172/JCI93303.CrossRefPubMedPubMedCentral

37.

Bournazos S, Wang TT, Dahan R, Maamary J, Ravetch JV. Signaling by antibodies: recent progress. Annu Rev Immunol. 2017;35:285–311. https://doi.org/10.1146/annurev-immunol-051116-052433.CrossRefPubMedPubMedCentral

38.

Warnders FJ, Lub-de Hooge MN, de Vries EGE, Kosterink JGW. Influence of protein properties and protein modification on biodistribution and tumor uptake of anticancer antibodies, antibody derivatives, and non-Ig scaffolds. Med Res Rev. 2018;38:1837–73. https://doi.org/10.1002/med.21498.CrossRefPubMed

39.

Dalziel M, Crispin M, Scanlan CN, Zitzmann N, Dwek RA. Emerging principles for the therapeutic exploitation of glycosylation. Science. 2014;343:1235681. https://doi.org/10.1126/science.1235681.CrossRefPubMed

40.

Pincetic A, Bournazos S, DiLillo DJ, Maamary J, Wang TT, Dahan R, et al. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat Immunol. 2014;15:707–16. https://doi.org/10.1038/ni.2939.CrossRefPubMedPubMedCentral

41.

Arlauckas SP, Garris CS, Kohler RH, Kitaoka M, Cuccarese MF, Yang KS, et al. In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci Transl Med. 2017;9. https://doi.org/10.1126/scitranslmed.aal3604.

42.

Ingram JR, Blomberg OS, Rashidian M, Ali L, Garforth S, Fedorov E, et al. Anti-CTLA-4 therapy requires an Fc domain for efficacy. Proc Natl Acad Sci U S A. 2018;115:3912–7. https://doi.org/10.1073/pnas.1801524115.CrossRefPubMedPubMedCentral

43.

Arce Vargas F, Furness AJS, Litchfield K, Joshi K, Rosenthal R, Ghorani E, et al. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies. Cancer Cell. 2018;33:649–63 e4. https://doi.org/10.1016/j.ccell.2018.02.010.CrossRefPubMedPubMedCentral

44.

Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. FcgammaRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28:285–95. https://doi.org/10.1016/j.ccell.2015.08.004.CrossRefPubMed

45.

Chakravarty R, Goel S, Cai W. Nanobody: the “magic bullet” for molecular imaging? Theranostics. 2014;4:386–98. https://doi.org/10.7150/thno.8006.CrossRefPubMedPubMedCentral

46.

Keyaerts M, Xavier C, Heemskerk J, Devoogdt N, Everaert H, Ackaert C, et al. Phase I study of 68Ga-HER2-nanobody for PET/CT assessment of HER2 expression in breast carcinoma. J Nucl Med. 2016;57:27–33. https://doi.org/10.2967/jnumed.115.162024.CrossRefPubMed

47.

Xing Y, Chand G, Liu C, Cook GJR, O’Doherty J, Zhao L, et al. Early phase I study of a (99m)Tc-labeled anti-programmed death ligand-1 (PD-L1) single-domain antibody in SPECT/CT assessment of PD-L1 expression in non-small cell lung cancer. J Nucl Med. 2019;60:1213–20. https://doi.org/10.2967/jnumed.118.224170.CrossRefPubMedPubMedCentral

Title: Development and characterization of CD54-targeted immunoPET imaging in solid tumors
Authors: Weijun Wei
Dawei Jiang
Hye Jin Lee
Miao Li
Christopher J. Kutyreff
Jonathan W. Engle
Jianjun Liu
Weibo Cai
Publication date: 01-11-2020
Publisher: Springer Berlin Heidelberg
Keywords: Solid Tumor
Melanoma
Melanoma
Thyroid Cancer
Thyroid Cancer
Thyroid Cancer
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-020-04784-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Development and characterization of CD54-targeted immunoPET imaging in solid tumors

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 12/2020

In reply to letter to the editor: radiomic feature analysis of pre-treatment FDG PET-CT for predicting outcome in anal squamous cell carcinoma

Whole liver segmentation based on deep learning and manual adjustment for clinical use in SIRT

Reliable quantification of 18F-GE-180 PET neuroinflammation studies using an individually scaled population-based input function or late tissue-to-blood ratio

Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease

Sanjiv Sam Gambhir obituary for EJNMMI

A rare case of polyostotic fibrous dysplasia detected on 18F-rhPSMA-7 PET/CT