Skip to main content

Advertisement

SpringerLink
Log in

Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

A Correction to this article was published on 12 January 2024

This article has been updated

Abstract

Purpose

Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30–60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC.

Methods

Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin–eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software.

Results

FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq.

Conclusion

89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

Original data are available on request.

Change history

References

  1. Pitt JJ, Riester M, Zheng Y, Yoshimatsu TF, Sanni A, Oluwasola O, et al. Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features. Nat Commun. 2018;9:4181. https://doi.org/10.1038/s41467-018-06616-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nagini S. Breast cancer: current molecular therapeutic targets and new players. Anticancer Agents Med Chem. 2017;17:152–63. https://doi.org/10.2174/1871520616666160502122724.

    Article  CAS  PubMed  Google Scholar 

  3. Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstet. 2016;293:247–69. https://doi.org/10.1007/s00404-015-3859-y.

    Article  CAS  PubMed  Google Scholar 

  4. Sukumar J, Gast K, Quiroga D, Lustberg M, Williams N. Triple-negative breast cancer: promising prognostic biomarkers currently in development. Expert Rev Anticancer Ther. 2021;21:135–48. https://doi.org/10.1080/14737140.2021.1840984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gianni-Barrera R, Butschkau A, Uccelli A, Certelli A, Valente P, Bartolomeo M, et al. PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation. Angiogenesis. 2018;21:883–900. https://doi.org/10.1007/s10456-018-9634-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kim W, Park A, Jang HH, Kim SE, Park KS. Breast tumor cell-stimulated bone marrow-derived mesenchymal stem cells promote the sprouting capacity of endothelial cells by promoting VEGF expression, mediated in part through HIF-1α increase. Cancers (Basel). 2022;14. https://doi.org/10.3390/cancers14194711.

  7. Sun H, Zhang D, Yao Z, Lin X, Liu J, Gu Q, et al. Anti-angiogenic treatment promotes triple-negative breast cancer invasion via vasculogenic mimicry. Cancer Biol Ther. 2017;18:205–13. https://doi.org/10.1080/15384047.2017.1294288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lau DK, Mencel J, Chau I. Safety and efficacy review of aflibercept for the treatment of metastatic colorectal cancer. Expert Opin Drug Saf. 2022;21:589–97. https://doi.org/10.1080/14740338.2022.2008905.

    Article  CAS  PubMed  Google Scholar 

  9. Azanza Perea JR, Sádaba B. Aflibercept. An approach to pharmacology. Arch Soc Esp Oftalmol. 2015;90(Suppl 1):6–10. https://doi.org/10.1016/s0365-6691(15)30003-4.

    Article  PubMed  Google Scholar 

  10. Eissing T, Stewart MW, Qian CX, Rittenhouse KD. Durability of VEGF suppression with intravitreal aflibercept and brolucizumab: using pharmacokinetic modeling to understand clinical outcomes. Transl Vis Sci Technol. 2021;10:9. https://doi.org/10.1167/tvst.10.4.9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jiang D, Xu T, Zhong L, Liang Q, Hu Y, Xiao W, et al. Research progress of VEGFR small molecule inhibitors in ocular neovascular diseases. Eur J Med Chem. 2023;257: 115535. https://doi.org/10.1016/j.ejmech.2023.115535.

    Article  CAS  PubMed  Google Scholar 

  12. Thakur A, Chorawala MR, Patel RS. A systemic review and meta-analysis of Aflibercept plus FOLFIRI regimen as a second-line treatment for metastatic colorectal cancer: A PRISMA compliant pooled analysis of randomized controlled trials and single arm studies to assess efficacy and safety. Crit Rev Oncol Hematol. 2023;188: 104034. https://doi.org/10.1016/j.critrevonc.2023.104034.

    Article  PubMed  Google Scholar 

  13. Erol C, Sendur Mehmet AN, Bilgetekin I, Garbioglu DB, Hamdard J, Akbas S, et al. Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group. J Cancer Res Ther. 2022;18:S347–53. https://doi.org/10.4103/jcrt.jcrt_1104_21.

    Article  CAS  PubMed  Google Scholar 

  14. Nakatsumi H, Komatsu Y, Muranaka T, Yuki S, Kawamoto Y, Harada K, et al. Study protocol for HGCSG1801: a multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies. Front Oncol. 2022;12: 939425. https://doi.org/10.3389/fonc.2022.939425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Raga MG, Pérez IP, Veiga RC, Sosa MM, Aguilera MJS, Rodríguez PL, et al. Maintenance of angiogenesis inhibition with aflibercept after progression to bevacizumab in metastatic colorectal cancer: real life study in the Valencian community. Clin Transl Oncol. 2023;25:1455–62. https://doi.org/10.1007/s12094-022-03047-8.

    Article  CAS  PubMed  Google Scholar 

  16. García García Y, Marín Alcalá M, Martínez VC. Anti-angiogenic therapy for ovarian cancer. EJC Suppl. 2020;15:77–86. https://doi.org/10.1016/j.ejcsup.2020.02.003.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Andersson Y, Fleten KG, Abrahamsen TW, Reed W, Davidson B, Flatmark K. Anti-angiogenic treatment in Pseudomyxoma peritonei-still a strong preclinical rationale. Cancers (Basel). 2021;13. https://doi.org/10.3390/cancers13112819.

  18. Perez K, Kulke MH, Horick NK, Regan E, Graham C, Scheutz S, et al. A phase II study of ziv-aflibercept in patients with advanced extrapancreatic neuroendocrine tumors. Pancreas. 2022;51:763–8. https://doi.org/10.1097/mpa.0000000000002099.

    Article  CAS  PubMed  Google Scholar 

  19. Zhao P, Anami Y, Gao P, Fan X, Li L, Tsuchikama K, et al. Enhanced anti-angiogenetic effect of transferrin receptor-mediated delivery of VEGF-trap in a glioblastoma mouse model. MAbs. 2022;14:2057269. https://doi.org/10.1080/19420862.2022.2057269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shi H, Guo N, Zhao Z, Liu L, Ni T, Zhang J, et al. Comparison of the second-line treatments for patients with small cell lung cancer sensitive to previous platinum-based chemotherapy: a systematic review and Bayesian network analysis. Front Oncol. 2023;13:1154685. https://doi.org/10.3389/fonc.2023.1154685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Camera S, Deleporte A, Bregni G, Trevisi E, Pretta A, Telli TA, et al. Momentum: a phase I trial investigating 2 schedules of capecitabine with aflibercept in patients with gastrointestinal and breast cancer. Clin Colorectal Cancer. 2020;19:311-8.e1. https://doi.org/10.1016/j.clcc.2020.05.007.

    Article  PubMed  Google Scholar 

  22. Wu FT, Paez-Ribes M, Xu P, Man S, Bogdanovic E, Thurston G, et al. Aflibercept and Ang1 supplementation improve neoadjuvant or adjuvant chemotherapy in a preclinical model of resectable breast cancer. Sci Rep. 2016;6:36694. https://doi.org/10.1038/srep36694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sideras K, Dueck AC, Hobday TJ, Rowland KM Jr, Allred JB, Northfelt DW, et al. North central cancer treatment group (NCCTG) N0537: phase II trial of VEGF-trap in patients with metastatic breast cancer previously treated with an anthracycline and/or a taxane. Clin Breast Cancer. 2012;12:387–91. https://doi.org/10.1016/j.clbc.2012.09.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kang L, Li C, Yang Q, Sutherlin L, Wang L, Chen Z, et al. (64)Cu-labeled daratumumab F(ab’)(2) fragment enables early visualization of CD38-positive lymphoma. Eur J Nucl Med Mol Imaging. 2022;49:1470–81. https://doi.org/10.1007/s00259-021-05593-9.

    Article  CAS  PubMed  Google Scholar 

  25. Kang L, Jiang D, England CG, Barnhart TE, Yu B, Rosenkrans ZT, et al. ImmunoPET imaging of CD38 in murine lymphoma models using (89)Zr-labeled daratumumab. Eur J Nucl Med Mol Imaging. 2018;45:1372–81. https://doi.org/10.1007/s00259-018-3941-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kang L, Li C, Rosenkrans ZT, Engle JW, Wang R, Jiang D, et al. Noninvasive evaluation of CD20 expression using (64)Cu-labeled F(ab’)(2) fragments of obinutuzumab in lymphoma. J Nucl Med. 2021;62:372–8. https://doi.org/10.2967/jnumed.120.246595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li C, Liu J, Yang X, Yang Q, Huang W, Zhang M, et al. Theranostic application of (64)Cu/(177)Lu-labeled anti-Trop2 monoclonal antibody in pancreatic cancer tumor models. Eur J Nucl Med Mol Imaging. 2022;50:168–83. https://doi.org/10.1007/s00259-022-05954-y.

    Article  CAS  PubMed  Google Scholar 

  28. Kang L, Li C, Rosenkrans ZT, Huo N, Chen Z, Ehlerding EB, et al. CD38-targeted theranostics of lymphoma with (89)Zr/(177)Lu-labeled daratumumab. Adv Sci (Weinh). 2021;8:2001879. https://doi.org/10.1002/advs.202001879.

    Article  CAS  PubMed  Google Scholar 

  29. Li C, Kang L, Fan K, Ferreira CA, Becker KV, Huo N, et al. ImmunoPET of CD146 in orthotopic and metastatic breast cancer models. Bioconjug Chem. 2021;32:1306–14. https://doi.org/10.1021/acs.bioconjchem.0c00649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li C, Yang Q, Chen Z, Qiu Y, Du Y, Wang R, et al. Noninvasive evaluation of multidrug resistance via imaging of ABCG2/BCRP multidrug transporter in lung cancer xenograft models. Mol Pharm. 2022;19:3521–9. https://doi.org/10.1021/acs.molpharmaceut.1c00939.

    Article  CAS  PubMed  Google Scholar 

  31. Du Y, Huo Y, Yang Q, Han Z, Hou L, Cui B, et al. Ultrasmall iron-gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET/MR imaging-guided ischemia stroke therapy. Exploration (Beijing). 2023;3:20220041. https://doi.org/10.1002/exp.20220041.

    Article  PubMed  Google Scholar 

  32. Saatci O, Kaymak A, Raza U, Ersan PG, Akbulut O, Banister CE, et al. Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Nat Commun. 2020;11:2416. https://doi.org/10.1038/s41467-020-16199-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yudistiro R, Hanaoka H, Katsumata N, Yamaguchi A, Tsushima Y. Bevacizumab radioimmunotherapy (RIT) with accelerated blood clearance using the avidin chase. Mol Pharm. 2018;15:2165–73. https://doi.org/10.1021/acs.molpharmaceut.8b00027.

    Article  CAS  PubMed  Google Scholar 

  34. Mery B, Rowinski E, Vallard A, Jacquin JP, Simoens X, Magné N, et al. Advocacy for a new oncology research paradigm: the model of bevacizumab in triple-negative breast cancer in a French cohort study. Oncology. 2019;97:1–6. https://doi.org/10.1159/000499583.

    Article  PubMed  Google Scholar 

  35. Korobelnik JF, Larsen M, Eter N, Bailey C, Wolf S, Schmelter T, et al. Efficacy and safety of intravitreal aflibercept treat-and-extend for macular edema in central retinal vein occlusion: the CENTERA study. Am J Ophthalmol. 2021;227:106–15. https://doi.org/10.1016/j.ajo.2021.01.027.

    Article  PubMed  Google Scholar 

  36. Mitchell P, Holz FG, Hykin P, Midena E, Souied E, Allmeier H, et al. Efficacy and safety of intravitreal aflibercept using a treat-and-extend regimen for neovascular age-related macular degeneration: the ARIES study: a randomized clinical trial. Retina. 2021;41:1911–20. https://doi.org/10.1097/iae.0000000000003128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jhaveri CD, Glassman AR, Ferris FL 3rd, Liu D, Maguire MG, Allen JB, et al. Aflibercept monotherapy or bevacizumab first for diabetic macular edema. N Engl J Med. 2022;387:692–703. https://doi.org/10.1056/NEJMoa2204225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Stahl A, Sukgen EA, Wu WC, Lepore D, Nakanishi H, Mazela J, et al. Effect of intravitreal aflibercept vs laser photocoagulation on treatment success of retinopathy of prematurity: the FIREFLEYE randomized clinical trial. JAMA. 2022;328:348–59. https://doi.org/10.1001/jama.2022.10564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Malekian S, Rahmati M, Sari S, Kazemimanesh M, Kheirbakhsh R, Muhammadnejad A, et al. Expression of diverse angiogenesis factor in different stages of the 4T1 tumor as a mouse model of triple-negative breast cancer. Adv Pharm Bull. 2020;10:323–8. https://doi.org/10.34172/apb.2020.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Breeman WA, van der Wansem K, Bernard BF, van Gameren A, Erion JL, Visser TJ, et al. The addition of DTPA to [177Lu-DOTA0, Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity. Eur J Nucl Med Mol Imaging. 2003;30:312–5. https://doi.org/10.1007/s00259-002-1054-4.

    Article  CAS  PubMed  Google Scholar 

  41. Li WP, Ma DS, Higginbotham C, Hoffman T, Ketring AR, Cutler CS, et al. Development of an in vitro model for assessing the in vivo stability of lanthanide chelates. Nucl Med Biol. 2001;28:145–54. https://doi.org/10.1016/s0969-8051(00)00196-7.

    Article  PubMed  Google Scholar 

  42. Hicks RJ, Hofman MS. Is there still a role for SPECT-CT in oncology in the PET-CT era? Nat Rev Clin Oncol. 2012;9:712–20. https://doi.org/10.1038/nrclinonc.2012.188.

    Article  CAS  PubMed  Google Scholar 

  43. Sabet A, Haug AR, Eiden C, Auernhammer CJ, Simon B, Bartenstein P, et al. Efficacy of peptide receptor radionuclide therapy with (177)Lu-octreotate in metastatic pulmonary neuroendocrine tumors: a dual-centre analysis. Am J Nucl Med Mol Imaging. 2017;7:74–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, Wansley EK, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203:1259–71. https://doi.org/10.1084/jem.20052494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hecht M, Eckstein M, Rutzner S, von der Grün J, Illmer T, Klautke G, et al. Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer. J Immunother Cancer. 2022;10. https://doi.org/10.1136/jitc-2021-003747.

  46. Fu DX, Tanhehco Y, Chen J, Foss CA, Fox JJ, Chong JM, et al. Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med. 2008;14:1118–22. https://doi.org/10.1038/nm.1864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sheng Y, You Y, Chen Y. Dual-targeting hybrid peptide-conjugated doxorubicin for drug resistance reversal in breast cancer. Int J Pharm. 2016;512:1–13. https://doi.org/10.1016/j.ijpharm.2016.08.016.

    Article  CAS  PubMed  Google Scholar 

  48. Chakraborty A, Hatzis C, DiGiovanna MP. Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease. Breast Cancer Res Treat. 2017;163:37–50. https://doi.org/10.1007/s10549-017-4169-9.

    Article  CAS  PubMed  Google Scholar 

  49. Chen M, Lin Z, Yao G, Hong X, Xue X, Chen L. A novel NIR fluorescent nanoprobe targeting HER2-positive breast cancer: Tra-TTR-A. Bioinorg Chem Appl. 2021;2021:2495958. https://doi.org/10.1155/2021/2495958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sun P, Qu F, Zhang C, Cheng P, Li X, Shen Q, et al. NIR-II excitation phototheranostic platform for synergistic photothermal therapy/chemotherapy/chemodynamic therapy of breast cancer bone metastases. Adv Sci (Weinh). 2022;9: e2204718. https://doi.org/10.1002/advs.202204718.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (82171970, 82202206), the Beijing Science Foundation for Distinguished Young Scholars (JQ21025), the Beijing Municipal Science & Technology Commission (Z221100007422027), Beijing Natural Science Foundation (7224365), National High Level Hospital Clinical Research Funding (Interdisciplinary Research Project of Peking University First Hospital, 2023IR17).

Author information

Author notes

  1. Qi Yang and Zhao Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Peking University First Hospital, No. 8 Xishiku Str., Xicheng Dist., Beijing, 100034, China

    Qi Yang, Zhao Chen, Yongkang Qiu, Wenpeng Huang, Tianyao Wang, Lele Song, Xinyao Sun & Lei Kang

  2. Department of Nuclear Medicine, Beijing Friendship Hospital Affiliated to Capital Medical University, 95 Yong’an Rd., Xicheng Dist., Beijing, 100050, China

    Cuicui Li

  3. Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, 100034, China

    Xiaojie Xu

Authors
  1. Qi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yongkang Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenpeng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tianyao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lele Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xinyao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cuicui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaojie Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lei Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Cuicui Li or Lei Kang.

Ethics declarations

Ethics approval

The study was approved by the Animal Committee of Peking University First Hospital (No. 2022018).

Consent to participate and publication

The requirement for informed consent was waived.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: The authors regret that the order of the names in the corresponding authors’ details section were interchanged. Dr. Kang should be listed before Dr. Li.

The original article has been corrected.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 112 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, Q., Chen, Z., Qiu, Y. et al. Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer. Eur J Nucl Med Mol Imaging 51, 1246–1260 (2024). https://doi.org/10.1007/s00259-023-06575-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-023-06575-9

Keywords

Search

Navigation