nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

09.07.2022 | Original Article

Anti-GD2 antibody for radiopharmaceutical imaging of osteosarcoma

verfasst von: Yingli Fu, Jing Yu, Ioanna Liatsou, Yong Du, Anders Josefsson, Jessie R. Nedrow, Hans Rindt, Jeffrey N. Bryan, Dara L. Kraitchman, George Sgouros

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 13/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Osteosarcoma (OS) is the most frequently diagnosed bone cancer in children with little improvement in overall survival in the past decades. The high surface expression of disialoganglioside GD2 on OS tumors and restricted expression in normal tissues makes it an ideal target for anti-OS radiopharmaceuticals. Since human and canine OS share many biological and molecular features, spontaneously occurring OS in canines has been an ideal model for testing new imaging and treatment modalities for human translation. In this study, we evaluated a humanized anti-GD2 antibody, hu3F8, as a potential delivery vector for targeted radiopharmaceutical imaging of human and canine OS.

Methods

The cross-reactivity of hu3F8 with human and canine OS cells and tumors was examined by immunohistochemistry and flow cytometry. The hu3F8 was radiolabeled with indium-111, and the biodistribution of [¹¹¹In]In-hu3F8 was assessed in tumor xenograft-bearing mice. The targeting ability of [¹¹¹In]In-hu3F8 to metastatic OS was tested in spontaneous OS canines.

Results

The hu3F8 cross reacts with human and canine OS cells and canine OS tumors with high binding affinity. Biodistribution studies revealed selective uptake of [¹¹¹In]In-hu3F8 in tumor tissue. SPECT/CT imaging of spontaneous OS canines demonstrated avid uptake of [¹¹¹In]In-hu3F8 in all metastatic lesions. Immunohistochemistry confirmed the extensive binding of radiolabeled hu3F8 within both osseous and soft lesions.

Conclusion

This study demonstrates the feasibility of targeting GD2 on OS cells and spontaneous OS canine tumors using hu3F8-based radiopharmaceutical imaging. Its ability to deliver an imaging payload in a targeted manner supports the utility of hu3F8 for precision imaging of OS and potential future use in radiopharmaceutical therapy.

Nur mit Berechtigung zugänglich

Roberts RD, Lizardo MM, Reed DR, Hingorani P, Glover J, Allen-Rhoades W, et al. Provocative questions in osteosarcoma basic and translational biology: a report from the Children’s Oncology Group. Cancer. 2019;125:3514–25. https://doi.org/10.1002/cncr.32351.CrossRefPubMed

Sampson VB, Gorlick R, Kamara D, Anders KE. A review of targeted therapies evaluated by the pediatric preclinical testing program for osteosarcoma. Front Oncol. 2013;3:132. https://doi.org/10.3389/fonc.2013.00132.CrossRefPubMedPubMedCentral

Gorlick R, Janeway K, Lessnick S, Randall RL, Marina N. Children’s Oncology Group’s 2013 blueprint for research: bone tumors. Pediatr Blood Cancer. 2013;60:1009–15. https://doi.org/10.1002/pbc.24429.CrossRefPubMed

Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer. 2014;14:722–35. https://doi.org/10.1038/nrc3838.CrossRefPubMed

Heiner JP, Miraldi F, Kallick S, Makley J, Neely J, Smith-Mensah WH, et al. Localization of GD2-specific monoclonal antibody 3F8 in human osteosarcoma. Cancer Res. 1987;47:5377–81.PubMed

Poon VI, Roth M, Piperdi S, Geller D, Gill J, Rudzinski ER, et al. Ganglioside GD2 expression is maintained upon recurrence in patients with osteosarcoma. Clin Sarcoma Res. 2015;5:4. https://doi.org/10.1186/s13569-014-0020-9.CrossRefPubMedPubMedCentral

Nazha B, Inal C, Owonikoko TK. Disialoganglioside GD2 expression in solid tumors and role as a target for cancer therapy. Front Oncol. 2020;10:1000. https://doi.org/10.3389/fonc.2020.01000.CrossRefPubMedPubMedCentral

Modak S, Le Luduec JB, Cheung IY, Goldman DA, Ostrovnaya I, Doubrovina E, et al. Adoptive immunotherapy with haploidentical natural killer cells and Anti-GD2 monoclonal antibody m3F8 for resistant neuroblastoma: results of a phase I study. Oncoimmunology. 2018;7: e1461305. https://doi.org/10.1080/2162402x.2018.1461305.CrossRefPubMedPubMedCentral

Butch ER, Mead PE, Amador Diaz V, Tillman H, Stewart E, Mishra JK, et al. Positron emission tomography detects in vivo expression of disialoganglioside GD2 in mouse models of primary and metastatic osteosarcoma. Cancer Res. 2019;79:3112–24. https://doi.org/10.1158/0008-5472.Can-18-3340.CrossRefPubMedPubMedCentral

10.

Roth M, Linkowski M, Tarim J, Piperdi S, Sowers R, Geller D, et al. Ganglioside GD2 as a therapeutic target for antibody-mediated therapy in patients with osteosarcoma. Cancer. 2014;120:548–54. https://doi.org/10.1002/cncr.28461.CrossRefPubMed

11.

Dobrenkov K, Cheung NK. GD2-targeted immunotherapy and radioimmunotherapy. Semin Oncol. 2014;41:589–612. https://doi.org/10.1053/j.seminoncol.2014.07.003.CrossRefPubMedPubMedCentral

12.

Cheung NK, Cheung IY, Kushner BH, Ostrovnaya I, Chamberlain E, Kramer K, et al. Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission. J Clin Oncol. 2012;30:3264–70. https://doi.org/10.1200/jco.2011.41.3807.CrossRefPubMedPubMedCentral

13.

Cheung NK, Guo H, Hu J, Tassev DV, Cheung IY. Humanizing murine IgG3 anti-GD2 antibody m3F8 substantially improves antibody-dependent cell-mediated cytotoxicity while retaining targeting in vivo. Oncoimmunology. 2012;1:477–86.CrossRef

14.

Markham A. Naxitamab: first approval. Drugs. 2021;81:291–6. https://doi.org/10.1007/s40265-021-01467-4.CrossRefPubMed

15.

Fenger JM, London CA, Kisseberth WC. Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology. ILAR J. 2014;55:69–85. https://doi.org/10.1093/ilar/ilu009.CrossRefPubMed

16.

MacEwen EG. Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment. Cancer Metastasis Rev. 1990;9:125–36.CrossRef

17.

Karkare S, Allen KJH, Jiao R, Malo ME, Dawicki W, Helal M, et al. Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors. Sci Rep. 2019;9:11476. https://doi.org/10.1038/s41598-019-47808-y.CrossRefPubMedPubMedCentral

18.

Westrøm S, Bønsdorff TB, Abbas N, Bruland ØS, Jonasdottir TJ, Mælandsmo GM, et al. Evaluation of CD146 as target for radioimmunotherapy against osteosarcoma. PLoS ONE. 2016;11: e0165382. https://doi.org/10.1371/journal.pone.0165382.CrossRefPubMedPubMedCentral

19.

Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov. 2020;19:589–608. https://doi.org/10.1038/s41573-020-0073-9.CrossRefPubMedPubMedCentral

20.

Miederer M, McDevitt MR, Borchardt P, Bergman I, Kramer K, Cheung NK, et al. Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application of alpha-emitting atomic nanogenerators targeting disialo-ganglioside GD2. Clin Cancer Res. 2004;10:6985–92. https://doi.org/10.1158/1078-0432.CCR-04-0859.CrossRefPubMed

21.

Senthamizhchelvan S, Hobbs RF, Song H, Frey EC, Zhang Z, Armour E, et al. Tumor dosimetry and response for 153Sm-ethylenediamine tetramethylene phosphonic acid therapy of high-risk osteosarcoma. J Nucl Med. 2012;53:215–24. https://doi.org/10.2967/jnumed.111.096677.CrossRefPubMed

22.

Brechbiel MW. Bifunctional chelates for metal nuclides. Q J Nucl Med Mol Imaging. 2008;52:166–73.PubMed

23.

Nedrow JR, Josefsson A, Park S, Ranka S, Roy S, Sgouros G. Imaging of programmed cell death ligand 1: impact of protein concentration on distribution of anti-PD-L1 SPECT agents in an immunocompetent murine model of melanoma. J Nucl Med. 2017;58:1560–6. https://doi.org/10.2967/jnumed.117.193268.CrossRefPubMedPubMedCentral

24.

Cortez A, Josefsson A, McCarty G, Shtekler AE, Rao A, Austin Z, et al. Evaluation of [(225)Ac]Ac-DOTA-anti-VLA-4 for targeted alpha therapy of metastatic melanoma. Nucl Med Biol. 2020;88–89:62–72. https://doi.org/10.1016/j.nucmedbio.2020.07.006.CrossRefPubMed

25.

Dobrenkov K, Ostrovnaya I, Gu J, Cheung IY, Cheung NK. Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults. Pediatr Blood Cancer. 2016;63:1780–5. https://doi.org/10.1002/pbc.26097.CrossRefPubMedPubMedCentral

26.

Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 2018;18:39–50. https://doi.org/10.1080/14737140.2018.1413939.CrossRefPubMed

27.

Beaino W, Nedrow JR, Anderson CJ. Evaluation of (68)Ga- and (177)Lu-DOTA-PEG4-LLP2A for VLA-4-targeted PET imaging and treatment of metastatic melanoma. Mol Pharm. 2015;12:1929–38. https://doi.org/10.1021/mp5006917[doi].

28.

Geller DS, Morris J, Revskaya E, Kahn M, Zhang W, Piperdi S, et al. Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R). Nucl Med Biol. 2016;43:812–7. https://doi.org/10.1016/j.nucmedbio.2016.07.008.CrossRefPubMedPubMedCentral

29.

Li HK, Hasegawa S, Nakajima NI, Morokoshi Y, Minegishi K, Nagatsu K. Targeted cancer cell ablation in mice by an α-particle-emitting astatine-211-labeled antibody against major histocompatibility complex class I chain-related protein A and B. Biochem Biophys Res Commun. 2018;506:1078–84. https://doi.org/10.1016/j.bbrc.2018.10.157.CrossRefPubMed

30.

Park JS, Withers SS, Modiano JF, Kent MS, Chen M, Luna JI, et al. Canine cancer immunotherapy studies: linking mouse and human. J Immunother Cancer. 2016;4:97. https://doi.org/10.1186/s40425-016-0200-7.CrossRefPubMedPubMedCentral

31.

Magee K, Marsh IR, Turek MM, Grudzinski J, Aluicio-Sarduy E, Engle JW, et al. Safety and feasibility of an in situ vaccination and immunomodulatory targeted radionuclide combination immuno-radiotherapy approach in a comparative (companion dog) setting. PLoS ONE. 2021;16: e0255798. https://doi.org/10.1371/journal.pone.0255798.CrossRefPubMedPubMedCentral

32.

Broqueza J, Prabaharan CB, Andrahennadi S, Allen KJH, Dickinson R, MacDonald-Dickinson V, et al. Novel human antibodies to insulin growth factor 2 receptor (IGF2R) for radioimmunoimaging and therapy of canine and human osteosarcoma. Cancers (Basel). 2021;13. doi:https://doi.org/10.3390/cancers13092208.

33.

Broqueza J, Prabaharan CB, Allen KJH, Jiao R, Fisher DR, Dickinson R, et al. Radioimmunotherapy targeting IGF2R on canine-patient-derived osteosarcoma tumors in mice and radiation dosimetry in canine and pediatric models. Pharmaceuticals (Basel). 2021;15. doi:https://doi.org/10.3390/ph15010010.

34.

F Navid PM Sondel R Barfield BL Shulkin RA Kaufman JA Allay et al 2014 Phase I trial of a novel anti-GD2 monoclonal antibody Hu14.18K322A designed to decrease toxicity in children with refractory or recurrent neuroblastoma J Clin Oncol. 32 1445 52 https://doi.org/10.1200/jco.2013.50.4423

Titel: Anti-GD2 antibody for radiopharmaceutical imaging of osteosarcoma
verfasst von: Yingli Fu
Jing Yu
Ioanna Liatsou
Yong Du
Anders Josefsson
Jessie R. Nedrow
Hans Rindt
Jeffrey N. Bryan
Dara L. Kraitchman
George Sgouros
Publikationsdatum: 09.07.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 13/2022
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05888-5

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 13/2022

Long-term test-retest of cerebral [18F]MK-6240 binding and longitudinal evaluation of extracerebral tracer uptake in healthy controls and amnestic MCI patients

Hetero-bivalent agents targeting FAP and PSMA

[89Zr]Zr-PSMA-617 PET/CT in biochemical recurrence of prostate cancer: first clinical experience from a pilot study including biodistribution and dose estimates

18F-FDG PET/CT findings of mesenchymal hamartoma of the liver in an adolescent

An encoder-decoder network for direct image reconstruction on sinograms of a long axial field of view PET

Visualisation of pelvic autonomic nerves using NIR-II fluorescence imaging